ChemPhysChem 25, e202400040 (2024)

DOI: 10.1002/cphc.202400040  (OpenAccess)

An ab Initio Study of High-Energetic Trioxatriazinane Derivatives: Conformational Analysis, Nitrogen Inversion, Heats of Formation, Dissociation Reaction, and Dimerization

High-energetic materials belong to two main classes: propellants and explosives. The still rather unexplored family of 1,3,5,2,4,6-trioxatriazinanes, N3O3R3, has a representative of each class. We have selected three compounds, R = H, R = CH3 and R = NO2, this last compound being known as TNTOTA, "trinitro-trioxa-triazinane". Of these compounds we have studied the conformational analysis, the nitrogen inversion, the heats of formation, and the dissociation reaction into the three monomers. In addition, the corresponding 1,3,2,4-dioxadiazetidines (N2O2R2) have also been studied.

ChemPhysChem 25, e202300809 (2024)

DOI: 10.1002/cphc.202300809  (OpenAccess)

Towards 2D Borane Chemistry in Hexagonal Cyclic Compounds

A comprehensive comparison between known benzene mono-substituted compounds R-Ph and the corresponding isoelectronic unknown R-cyclohexaborane(12) molecules is carried out from a geometric and electronic structure point of view, with R = {H, BH2, CH3, NH2, OH, F ; AlH2, SiH3, PH2, SH, Cl ; NO2 , OCH3}. We suggest new chemical names for the 2D borane compounds and analyze the geometric and electronic structure carbon vs. boron comparatives by means of HOMO-LUMO gaps, bonding schemes, electron density topological properties and predicted NMR chemical shifts. The predictions on the properties in planar hexagonal cyclic boranes may help in the design of synthesis procedures for these yet-unkown compounds.

Struct. Chem. 34, 391–398 (2023)

DOI: 10.1007/s11224-023-02130-2  (OpenAccess)

The dubious origin of beryllium toxicity

Four mechanisms have been proposed in the literature to explain beryllium toxicity; they can be divided in two groups of two mechanisms: (i) replacement type: models 1 and 2; (ii) addition type: models 3 and 4. At this moment is not possible to select the best model not even to establish if one of these models will be the ultimate mechanism of beryllium toxicity. However, it is important to know the still open discussion about something so important associated with one of the simplest elements of the periodic table.

Theor. Chem. Acc. 28, 142 (2023)

DOI: 10.1007/s00214-023-02967-0   (OpenAccess)

Dramatic effect of the nature of R on the intrinsic acidity and basicity of potential astrochemical R–C≡COH and R–C≡CSH compounds

The effect of changing the nature of the R substituent from the first row (H, Li, BeH, BH2, CH3, NH2, OH and F) to second row (Na, MgH, AlH2, SiH3, PH2, SH and Cl) on the intrinsic acidity and basicity of R–C≡COH and R–C≡CSH compounds was investigated through the use of G4 high-level ab initio calculation. The variation of the acidity and basicity of the R–C≡CSH derivatives as a function of R is practically parallel to that found for the corresponding R–C≡COH analogs; though the basicities of the former are 9–14% higher than those of the latter, the acidity gap being very small (~ 2%). When this analysis is extended to the derivatives in which the triple CC bond is replaced by a double or single bond, it is found that the acidity gap increases systematically as the CC bond goes from triple to single; whereas, as expected for the basicity, the trend is the opposite. Quite surprisingly, however, the variation of the basicity of R–C≡CX (X = OH, SH) compounds with the nature of the first-row substituents, R, is remarkably different from that produced by the second-row analogs. The same is observed as far as intrinsic acidities are concerned. These dissimilarities reflect the rather different changes in the strength of the CC and the CX (X = OH, SH) bonds when a first-row substituent is replaced by the second-row analog, as reflected in the atoms in molecules (AIM), natural bond orbital (NBO) and the electron localization function (ELF) analyses of the corresponding species.

J. Phys. Chem. A 127, 468–476 (2023)

DOI: 10.1021/acs.jpca.2c07693  (OpenAccess)

Linking the Interatomic Exchange-Correlation Energy to Experimental J-Coupling Constants

The main aim of the current work is to find an experimental connection to the interatomic exchange-correlation energy as defined by the energy decomposition method Interacting Quantum Atoms (IQA). A suitable candidate as (essentially) experimental quantity is the nuclear magnetic resonance (NMR) J-coupling constant denoted 3J(H,H′), which a number of previous studies showed to correlate well with QTAIM’s delocalization index (DI), which is essentially a bond order. Inspired by Karplus equations, here, we investigate correlations between 3J(H,H′) and a relevant dihedral angle in six simple initial compounds of the shape H3C-YHn (Y = C, N, O, Si, P, and S), N-methylacetamide (as prototype of the peptide bond), and five peptide-capped amino acids (Gly, Ala, Val, Ile, and Leu) because of the protein direction of the force field FFLUX. In conclusion, except for methanol, the inter-hydrogen exchange-correlation energy Vxc(H,H′) makes the best contact with experiment, through 3J(H,H′), when multiplied with the internuclear distance RHH′.

J. Comput. Chem. 44, 159-167 (2023)

DOI: 10.1002/jcc.26843  (OpenAccess)

Dismantlement of ammonia upon interaction with Ben (n ≤ 10) clusters

The interaction of ammonia with Ben (n < 1–10) clusters has been investigated by density functional theory and ab initio calculations. The main conclusion is that, regardless of the size of the Be cluster, neither the structure of ammonia nor that of the Be clusters are preserved due to a systematic dissociation of its N-H bonds and a spontaneous H-shift toward the available Be atoms. This H migration not only leads to rather stable Be-H bonds, but dramatically enhances the strength of the Be-N bonds as well. Accordingly, the maximum stability is found for the interaction with the beryllium trimer, leading to a complex with three N-Be and three Be-H bonds. Another maximum in stability, although lower than that reached for n = 3, is found for the Be heptamer, since from n = 6, a new N-Be bond is formed, so that complexes from n = 6 to n = 10 are characterized by the formation of a NBe4 moiety, whose stability reaches a maximum at n = 7. The bonding characteristics of the different species formed are analyzed by means of AIM, NBO, ELF and AdNDP approaches.

Comput. Theor. Chem. 1220, 113987 (2023)

DOI: 10.1016/j.comptc.2022.113987

A quantum-chemical study of boro-fullerenes B60H60, B60F30H30, and B60F60

The one-to-one structural correspondence between any conjugated hydrocarbon CnHm and the borane BnHm+n is extended here to pure conjugated carbon systems. We study the closo-borane B60H60 system, isoelectronic with the Buckminsterfullerene C60, and the fluorine substituted systems B60F30H30 and B60F60, all of them with icosahedral Ih symmetry. All these systems, except B60(F30)in(H30)out, correspond to energy minima in the potential energy hypersurface. Selected electronic structure methods are used to characterize these molecules: molecular electrostatic potentials (MEP), atomic charges, bond orders, and topological properties of the electron density within the quantum theory of atoms-in-molecules (QTAIM) and electron localization function (ELF) theory. In the particular case of B60H60 we use the recently developed Hückeloid model for planar boranes. The stability of the energy minimum of the B60F60 icosahedral structure could have its origin in F···F attractive interactions of the inner fluorine atoms of the cage.


Chem. Phys. Lett. 806, 140051 (2022)

DOI: 10.1016/j.cplett.2022.140051 (OpenAccess)

The reciprocal SN2 and SE2 reactions of ammonia borane

The reactions here explored are microscopic analogs of Newton cradle: left thing attack, right thing leaves and central thing remains unaffected. We have studied symmetric SX2 reactions, X  = N or E, where the attacking and leaving molecules are the same: H3N, H3B, H3C(–) and the central molecules are H3B (SN2@B), H3N (SE2) or H3C (SN2@C). Non-symmetric reactions with different initial and final complexes were also studied and examples where the elements of the lateral molecules differ, P vs N.

Graphical Abstract designed by Iñigo Irribarren

J. Org. Chem. 87, 8118–8125 (2022)

DOI: 10.1021/acs.joc.2c00845

Rotational Behavior of N-(5-Substituted-pyrimidin-2-yl)anilines: Relayed Electronic Effect in Two N–Ar Bond Rotations

N-Methyl-2-methoxymethylanilines 1 bearing various 5-substituted-pyrimidin-2-yl groups were prepared, and their rotational behaviors were explored in detail. It was revealed that the rotational barriers around two N–Ar bonds increase in proportion to the electron-withdrawing ability of substituents X at the 5-position.

ACS Sens. 7, 322–330 (2022)

DOI: 10.1021/acssensors.1c02439  (OpenAccess)

Self-Assembled Lanthanide Antenna Glutathione Sensor for the Study of Immune Cells

The small molecule 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-carboxylic acid (2b) behaves as a reactive non-fluorescent Michael acceptor, which after reaction with thiols becomes fluorescent, and an efficient Eu3+ antenna, after self-assembling with this cation in water. This behavior makes 2b a highly selective GSH biosensor, which has demonstrated high potential for studies in murine and human cells of the immune system (CD4+ T, CD8+ T, and B cells) using flow cytometry. GSH can be monitored by the fluorescence of the product of addition to 2b (445 nm) or by the luminescence of Eu3+ (592 nm). 2b was able to capture baseline differences in GSH intracellular levels among murine and human CD4+ T, CD8+ T, and B cells. We also successfully used 2b to monitor intracellular changes in GSH associated with the metabolic variations governing the induction of CD4+ naïve T cells into regulatory T cells (TREG).


Mini-Rev. Org. Chem. 19, 138-145 (2022)

DOI: 10.2174/1570193X18666210225121327

Polyhedra, Tiles and Graphene Defects: The Case of Tetraoctite

This mini review concerns hydrocarbons, (CH)n, and carbon allotropes, Cn, and their relationships with regular solids and regular surfaces, respectively. Platonic and Archimedean solids and surfaces related to carbon allotropes are described as an introduction. An overview is then provided on how Stone-Wales defects lead to a series of structures: pentaheptite, Haeckelite, net C, net W, planar C4, biphenylene, graphyne, graphdiyne, and tetraoctite. This last compound is discussed in detail together with its relation to the Mills-Nixon effect on cyclooctatetraene (COT).

Struct. Chem. 32, 1755–1761 (2021)

DOI: 10.1007/s11224-021-01805-y  (OpenAccess)

The SN2 reaction and its relationship with the Walden inversion, the Finkelstein and Menshutkin reactions together with theoretical calculations for the Finkelstein reaction

This communication gives an overview of the relationships between four reactions that although related were not always perceived as such: SN2, Walden, Finkelstein, and Menshutkin. Binary interactions (SN2 & Walden, SN2 & Menshutkin, SN2 & Finkelstein, Walden & Menshutkin, Walden & Finkelstein, Menshutkin & Finkelstein) were reported. Carbon, silicon, nitrogen, and phosphorus as central atoms and fluorides, chlorides, bromides, and iodides as lateral atoms were considered. Theoretical calculations provide Gibbs free energies that were analyzed with linear models to obtain the halide contributions. The M06-2x DFT computational method and the 6-311++G(d,p) basis set have been used for all atoms except for iodine where the effective core potential def2-TZVP basis set was used. Concerning the central atom pairs, carbon/silicon vs. nitrogen/phosphorus, we reported here for the first time that the effect of valence expansion was known for Si but not for P. Concerning the lateral halogen atoms, some empirical models including the interaction between F and I as entering and leaving groups explain the Gibbs free energies.

Arkivoc viii, 265-276 (2021)

DOI: 10.24820/ark.5550190.p011.489  (OpenAccess)

High yield synthesis of trans-azoxybenzene versus 2-isopropoxy-4-nitrobenzoic acid: influence of temperature and base concentration

The reported two-step synthesis of 2-isopropoxy-4-nitrobenzoic acid from 2-hydroxy-4-nitrobenzoic acid, using iodopropane/K2CO3 and subsequent hydrolysis of the isopropyl 2-isopropoxy-4-nitrobenzoate intermediate with 45% NaOH/THF-EtOH at 80 °C, was reconsidered. (Z)-1,2-bis(4-carboxy-3- isopropoxyphenyl)diazene-1-oxide derivative (3), which was isolated as main product (92%) of the reaction, was characterized by IR, 1H, 13C, and 15N NMR spectroscopy. The 15N chemical shifts were consistent with the trans-configuration for this azoxybenzene derivative. As an alternative, synthesis of 2-isopropoxy-4- nitrobenzoic acid was accomplished in high yield (82%) working at room temperature and using lithium hydroxide instead of concentrate NaOH. Incorrect reaction temperature report or measurement in the published protocol (J. Org. Chem. 2011, 76, 7040) probably accounts for the discrepancies with our findings.

ChemPhysChem 22, 764–774 (2021)

DOI: 10.1002/cphc.202001010

A Density Functional Theory Study of Optical Rotation in Some Aziridine and Oxirane Derivatives

We present time‐dependent density functional theory (TDDFT) calculations of the electronic optical rotation (ORP) for seven oxirane and two aziridine derivatives in the gas phase and in solution and compare the results with the available experimental values. For seven of the studied molecules it is the first time that their optical rotation was studied theoretically and we have therefore investigated the influence of several settings in the TDDFT calculations on the results. This includes the choice of the one‐electron basis set, the exchange‐correlation functional or the particular polarizable continuum model (PCM). We can confirm that polarized quadruple zeta basis sets augmented with diffuse functions are necessary for converged results and find that the aug‐pc‐3 basis set is a viable alternative to the frequently employed aug‐cc‐pVQZ basis set. Based on our study, we cannot recommend the generalized gradient functional KT3 for calculations of the ORP in these compounds, whereas the hybrid functional PBE0 gives results quite similar to the long‐range correct CAM−B3LYP functional. Finally, we observe large differences in the solvent effects predicted by the integral equation formalism of PCM and the SMD variant of PCM. For the majority of solute/solvent combinations in this study, we find that the SMD model in combination with the PBE0 functional and the aug‐pc‐3 basis set gives the best agreement with the experimental values.

J. Mol. Struct. 1229, 129614, (2021)

DOI: 10.1016/j.molstruc.2020.129614

Zinc(II) complexes derived from 2-formylpyridine nicotinoyl hydrazone as organic blocker: Syntheses, crystal architectures, Hirshfeld surface analyses and DFT studies

In this work we report new discrete mononucler heteroleptic zinc(II) halido complexes of the type [Zn(Hal)2HL] (Hal = Cl, 1; Br, 2) and zinc(II) pseudohalido complex [Zn(NCS)2HL]·1.5MeOH (3·1.5MeOH) (HL = 2-formylpyridine nicotinoyl hydrazone). Single crystal X-ray diffraction revealed that in the structures of complexes 1–3, the Zn(II) metal atom is in a five-coordinated coordination environment and adopts a distorted square pyramidal chromophore, formed by one N2O tridentate chelator HL and two halides or thiocyanates, respectively. All complexes display a very similar molecular structure and complexes 1 and 2 are fully isostructural. Crystal packing of 1 and 2 is mainly dictated by the bifurcated N–H···Hal and linear C–H···Hal hydrogen bonds, yielding 1D polymeric chains, which additionally stabilized by intermolecular stacking interactions of the types ZnOCNN···ZnOCNN, ZnOCNN···ZnNCCN and 2-Py···3-Py. These 1D chains are interlinked into a 3D network through C–H···Hal interactions. Crystal packing of 3·1.5MeOH is constructed from centrosymmetric dimers formed through linear N–H···O and O–H···N hydrogen bonds, yielding a hydrogen bonded synthon of motif R44(16). These dimers are interlinked trough the C–S···ZnNCCN interactions, yielding 1D polymeric chains, which, in turn, are interlinked through the C–H···O bonds, and ZnNCCN···3-Py and 3-Py···3-Py stacking interactions into a 3D framework. Hirshfeld surface analysis, employed to gain additional insight into interactions responsible for the packing of complexes, and quantitative examination of 2D fingerprint plots revealed that the most important factors in the crystal packing are H···Hal and and H···H contacts in 1 and 2, and H···H, H···N, H···C and H···S contacts in 3, further supported by C···C contacts. Density function theory (DFT) calculations were performed to gather more information into structure and bonding since they play an important role in the construction of 3D supramolecular frameworks.

New J. Chem. 45, 2742-2753 (2021)

DOI: 10.1039/d0nj05232a

Tetranuclear copper(II) cubane complexes derived from self-assembled 1,3-dimethyl-5-(o-phenolateazo)-6-aminouracil: structures, non-covalent interactions and magnetic property

Tetranuclear copper(II) complexes are of paramount importance in structural biology, and they are potential materials for magnetism and catalysis. To develop such a system, a new 6-aminoazouracil ligand, 1,3-dimethyl-5-(o-phenolate-azo)-6-aminouracil (H2L, 1) with a NuNaO (Nu, uracil-N and Na, azo-N) chromophore was synthesized and used to generate a noble discrete doubly opened Cu4O4 cubane-like cluster ([CuL]4·2H2O, 2.2H2O) for studying magnetism. The coordination environment of Cu(II) is distorted square planar linked through phenolate-μ2-O bridges. The ligand crystallizes in the monoclinic space group P121/c1 and the complex is in the tetragonal I41/a space group with an S4 symmetry. The ligand has two dissociable hydrogen atoms in the solution with pK1 4.91 (hydrazone proton) and pK2 9.68 (phenolic proton). In the solid state, the ligand exhibits displaced stacking (energy, −69.5 and −77.3 kJ mol−1 for the molecules A and B, respectively) and tetrel bonding interactions (energy, −43.8 kJ mol−1). In 2.2H2O, the symmetrical units are stacked to show weak noncovalent interactions. The magnetic property of 2.2H2O was investigated based on the cubane [Cu4O4] core and discussed in detail, resulting in the exchange coupling parameter [(J1 (short Cu⋯Cu distances) = −110.1(1) cm−1, J2 (long Cu⋯Cu distances) = −27.1(2) cm−1)] that indicate a strong antiferromagnetic interaction between tetranuclear copper(II) ions through μ-phenolate linkers, which is a result of the interaction of dx2−y2 orbitals in the square plane. The EPR study is concomitant with the results of magnetism. Thus, it could be a potential material in the field of antiferromagnetic spintronics as well.

Chemistry 3, 28-38 (2021)

DOI: 10.3390/chemistry3010003OpenAccess

On the 3D → 2D Isomerization of Hexaborane(12)

By following the intrinsic reaction coordinate connecting transition states with energy minima on the potential energy surface, we have determined the reaction steps connecting three-dimensional hexaborane(12) with unknown planar two-dimensional hexaborane(12). In an effort to predict the potential synthesis of finite planar borane molecules, we found that the reaction limiting factor stems from the breaking of the central boron-boron bond perpendicular to the C2 axis of rotation in three-dimensional hexaborane(12).

ChemPhysChem 21, 2460–2467 (2020)

DOI: 10.1002/cphc.202000554

Diborane Concatenation Leads to New Planar Boron Chemistry

Diborane has long been realized to be analogous to ethylene in terms of its bonding MOs, both as to symmetries and splitting patterns. This naturally suggests an investigation to see whether other similar conjugated hydrocarbons manifest a similar boron‐substituted and H2 supplemented borane. That is, for a conjugated hydrocarbon structure with a neighbor‐paired resonance pattern, we propose to look at boranes where each carbon atom is replaced by a boron atom, and an H‐atom pair is added to each double bond of the resonance structure, with one H above the molecular plane and one below. This construction of concatenated diboranes is uniformly different than that for the previously known stable boranes of 4 or more B atoms. We find from quantum‐chemical computations that our so constructed polyboranes are stable. All this suggests a possible novel new chapter in borane chemistry – a chapter with some promise of understandings related to that for (alternant) conjugated hydrocarbons.

Molecules 25, 5026 (2020)

DOI: 10.3390/molecules25215026  (OpenAccess)

Hybrid Boron‐Carbon Chemistry

The recently proved one-to-one structural equivalence between a conjugated hydrocarbon CnHm and the corresponding borane BnHm+n is applied here to hybrid systems, where each C=C double bond in the hydrocarbon is consecutively substituted by planar B(H2)B moieties from diborane(6). Quantum chemical computations with the B3LYP/cc-pVTZ method show that the structural equivalences are maintained along the substitutions, even for non-planar systems. We use as benchmark aromatic and antiaromatic (poly)cyclic conjugated hydrocarbons: cyclobutadiene, benzene, cyclooctatetraene, pentalene, benzocyclobutadiene, naphthalene and azulene. The transformation of these conjugated hydrocarbons to the corresponding boranes is analyzed from the viewpoint of geometry and electronic structure.

ACS Sens. 5, 9, 2792–2799 (2020)

DOI: 10.1021/acssensors.0c00587

Environment-Sensitive Probes for Illuminating Amyloid Aggregation In Vitro and in Zebrafish

The aberrant aggregation of certain peptides and proteins, forming extracellular plaques of fibrillar material, is one of the hallmarks of amyloid diseases, such as Alzheimer’s and Parkinson’s. Herein, we have designed a new family of solvatochromic dyes based on the 9-amino-quinolimide moiety capable of reporting during the early stages of amyloid fibrillization. We have rationally improved the photophysical properties of quinolimides by placing diverse amino groups at the 9-position of the quinolimide core, leading to higher solvatochromic and fluorogenic character and higher lifetime dependence on the hydrophobicity of the environment, which represent excellent properties for the sensitive detection of prefibrillar aggregates. Among the different probes prepared, the 9-azetidinyl-quinolimide derivative showed striking performance in the following β-amyloid peptide (Aβ) aggregation in solution in real time and identifying the formation of different types of early oligomers of Aβ, the most important species linked to cytotoxicity, using novel, multidimensional fluorescence microscopy, with one- or two-photon excitation. Interestingly, the new dye allowed the visualization of proteinaceous inclusion bodies in a zebrafish model with neuronal damage induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Our results support the potential of the novel fluorophores as powerful tools to follow amyloid aggregation using fluorescence microscopy in vivo, revealing heterogeneous populations of different types of aggregates and, more broadly, to study protein interactions.

Phosphorus Sulfur Silicon Relat Elem., 195, 307–313 (2020)

DOI: 10.1080/10426507.2019.1688812

Theoretical calculations of the chemical shifts of cyclo[n]phosphazenes for n = 2, 3, 4 and 5 (X2PN)n with X = CH3, F, Cl and Br: the effect of relativistic corrections

Di, tri, tetra and pentacyclophosphazenes substituted on the phosphorus atoms by CH3, F, Cl and Br atoms corresponding to (X2PN)n structures have been studied theoretically at the B3LYP/6-311++G(d,p) level. After a brief discussion of their geometries comparing them to those of the conjugated carbocycles, (CH)n, of the same size, the absolute shieldings calculated with the GIAO and ZORA approximations will be reported. For the Cl and mainly for the Br substituted cyclo[n]-phosphazenes, relativistic corrections are absolutely necessary for 31P and useful for 15N chemical shifts.

Struct. Chem. 31, 25-35 (2020)

DOI: 10.1007/s11224-019-01451-5

Theoretical studies of perimidine and its derivatives: structures, energies, and spectra

Theoretical calculations at the B3LYP/6-311++G(d,p) level plus GIAO calculations for NMR absolute shieldings have been carried out for the parent perimidine and several of its derivatives. These include its anion and cation and the acid-base equilibria and other examples of annular tautomerism, such as the 2-hydroxy (and their radical cations), 2-thiol, 2-amino, and 2-alkyl perimidines, and the functional tautomers, such as the benzologues of perimidone. The protonation of 2-aminoperimidines (cyclic guanidines) and the properties of perimidine carbene (dimerization and addition to carbon dioxide), biperimidine, dihydroperimidine, and spiro bidihydroperimidine were also studied.

Dyes Pigm. 175, 108172 (2020)

DOI: 10.1016/j.dyepig.2019.108172

Fluorescence mechanism switching from ICT to PET by substituent chemical manipulation: Macrophage cytoplasm imaging probes

The lack of polarity sensing fluorophores with OFF-ON features when increasing the environment polarity has limited the monitoring of biological processes that involve an increase in local hydrophilicity. In this work, replacement of a hydroxyl group by a dimethylamino group transformed solvatochromic ICT naphthalimide- and quinolimide-based fluorophores into reversed solvatochromic ones, with higher emission in polar than in apolar environments. Excited-state dynamics studies, TD-DFT calculations, X-ray and NMR support the existence of a folded conformation for the 2-(dimethylamino)ethyl chain upon the imide ring in apolar solvents, where the dimethylamino group would quench the fluorescence by a PET effect, while in polar solvents the chain has an extended conformation, where the PET is hindered. These PET fluorophores have given rise to H2O and pH sensors in organic solvents as well as to bright macrophage cytoplasm imaging probes.

Struct. Chem. 30, 2029-2055 (2019)

DOI: 10.1007/s11224-019-01370-5

Theoretical studies of conformational analysis and intramolecular dynamic phenomena

This review reports our computational studies of a variety of topics related to conformational analyses and intramolecular dynamic phenomena. Single and double bonds, open and ring systems, and chiral molecules devoid of chiral centers (atropisomers, propellers, scorpionates, helicenes, truxenes) will be reported. Studies that followed our contributions and that are related to them will also be cited. Some curious aspects such as the absence of influence of static fields on absolute chirality, the extension of CIP rules to supramolecular systems, libration of phenyl groups, and the barrier of 1,16-dehydro[6]helicene will be discussed.

Chem. Eur. J. 25, 10172–10178 (2019)

DOI: 10.1002/chem.201901666

Bond Length Alternation Observed Experimentally: The Case of 1H-Indazole

Bond length alternation is a chemical phenomenon in benzene rings fused to other rings, which has been mainly predicted theoretically. Its physical origin is still not clear and has generated discussion. Here, by using a strategy that combines microwave spectroscopy, custom‐made synthesis and high‐level ab initio calculations, we demonstrate that this phenomenon is clearly observed in the prototype indazole molecule isolated in the gas phase. The 1H‐indazole conformer was detected by rotational spectroscopy, and its 17 isotopologues resulting from single and double heavy atom substitution (13C and 15N) were also unambiguously observed. Several experimental structures were determined and, in particular, the most useful semi‐experimental equilibrium structure (reSE), allowed determination of the heavy atom bond lengths to milli‐Ångstrom precision. The experimentally determined bond length alternation is estimated to correspond to 60:40 contributions from the two resonant forms of 1H‐indazole.

New J. Chem. 43, 7831-7838 (2019)

DOI: 10.1039/C9NJ00824A (OpenAccess)

The extraordinary richness of the reaction between diazomethane and tetracyanoethylene: can computational calculations shed light on old papers?

In the quest of the structure of the intermediate between Δ1- and Δ2-pyrazolines, the reactivity of these molecules tetrasubstituted by cyano groups in adjacent positions (3,3,4,4 or 4,4,5,5) has been explored in their neutral and protonated forms. Many reactions reported in the literature for pyrazolines have been studied and quantified (energies and transition states). Thirty-three structures of pyrazolines, their open-ring counterparts and their complexes are described. Acid–base equilibria, rotations, electrocyclic reactions and sigmatropic transpositions are reported.

Struct. Chem. 30, 633-636 (2019)

DOI: 10.1007/s11224-018-1276-0

The strange case of achiral compounds which were reported to always crystallize in the same chiral group

In the present review, one of the mysteries of chemistry, the non-stochastic preference for one enantiomer during crystallization processes, is discussed with some examples of the literature and one published by our own group.

Acta Cryst. C75, 271-276 (2019)

DOI: 10.1107/S205322961900144X

The structure of the anti-aging agent J147 used for treating Alzheimer's disease

The molecular structure of the anti‐aging agent J147 [systematic name: (E)‐N‐(2,4‐dimethylphenyl)‐2,2,2‐trifluoro‐N′‐(3‐methoxybenzylidene)acetohydrazide], C18H17F3N2O2, has been determined at 150 K. The crystal structure corresponds to the minimum‐energy conformation in the gas phase calculated by density functional theory (DFT). 15 other conformations have been calculated and compared with the minimum, denoted 1111. NMR spectroscopic data have been obtained and compared with those from Gauge Independent Atomic Orbital (GIAO) calculations. DFT calculations allow the reduction of the 16 possible rotamers to the four most stable (i.e.1111, 1112, 1121 and 1222); in addition, the calculated barriers connecting these minima are low enough to permit their interconversion. Comparison of the NMR spectroscopic results, both experimental and calculated, point to the 1121 isomer being present in chloroform solution.

Theor. Chem. Acc. 138, 12 (2019)

DOI: 10.1007/s00214-018-2383-0

A relative energy gradient (REG) study of the planar and perpendicular torsional energy barriers in biphenyl

Biphenyl is a prototype molecule, the study of which is important for a proper understanding of stereo-electronic effects. In the gas phase it has an equilibrium central torsion angle of ~ 45° and shows both a planar (0°) and a perpendicular (90°) torsional energy barrier. The latter is analysed for the first time. We use the newly proposed REG method, which is an exhaustive procedure that automatically ranks atomic energy contributions according to their importance in explaining the energy profile of a total system. Here, the REG method operates on energy contributions computed by the interacting quantum atoms method. This method is minimal in architecture and provides a crisp picture of well-defined and well-separated electrostatic, steric and exchange (covalent) energies at atomistic level. It is shown that the bond critical point occurring between the ortho-hydrogens in the planar geometry has been wrongly interpreted as a sign of repulsive interaction. A convenient metaphor of analysing football matches is introduced to clarify the role of a REG analysis.

Inorg. Chim. Acta, 483, 402-410 (2018)

DOI: 10.1016/j.ica.2018.08.009

The structure of four thallium tris(1H-pyrazol-1-yl)hydroborates in the solid state by X-ray crystallography and in solution by NMR and DFT-GIAO calculations

The crystal and molecular structures of four thallium tris(1H-pyrazol-1-yl)hydroborates have been determined by X-ray analysis and compared with those recorded in the literature. The geometry of the pyrazole ring, steric effects of the substituents at position 3, packing and other characteristics of the crystals are discussed. Density Functional Theory-Gauge Invariant Atomic Orbital (DFT-GIAO) calculations have been carried out to determine the chemical shifts of the four compounds; they have been compared with experimental values finding an agreement excellent.


ChemistrySelect, 3, 4344-4353 (2018)

DOI: 10.1002/slct.201800683

Predicted Gas‐Phase and Liquid‐Phase Acidities of Carborane Carboxylic and Dicarboxylic Acids

By means of MP2 and DFT computations we predict gas‐phase acidities and liquid‐phase (MeCN) acidities of (di)carboxylic acids derived from icosahedral ortho, meta, and para‐carboranes. For comparative purpose, we include the benzoic and phthalic acids. Substitution of benzene by a carborane cage – cage effect – strikingly increases the gas‐phase acidity (lower GA) for the (di)carboxylic acids, being the ortho isomers always the most acidic, following the order ortho ≫ meta > para. The computed GA of the dicarboxylic acid derived from ortho‐carborane is far lower than sulphuric acid, due to an enhanced stabilization of the carboxylate through an intramolecular OHO bridge connection, also taking place in phthalic acid. The change of GA relative to ortho, metaand para positions of the carboxylic groups ‐ isomer effect ‐ is larger for carboranes. As regards to liquid‐phase (MeCN), the computations show that carborane (di)carboxylic acids also show a larger acidity (lower pKa) as compared to the phthalic acids and that the dicarboxylic ortho‐carborane is also a superacid in the liquid phase (MeCN), due to the OHO bridge connection in the carboxylate, as in the gas phase. Additional computations show how much of this isomeric effect is to be attributed to the electronic delocalization.

Analyst, 143, 1406-1416 (2018)

DOI: 10.1039/C7AN01855J

A vibrational circular dichroism (VCD) methodology for the measurement of enantiomeric excess in chiral compounds in the solid phase and for the complementary use of NMR and VCD techniques in solution: the camphor case

For the first time, the success of a methodology for the determination of enantiomeric excess (% ee) in chiral solid samples by vibrational circular dichroism (VCD) spectroscopy is reported. We have used camphor to determine the % ee in a blind sample constituted by a mixture of its two enantiomers as a test for the validity of our approach. IR and VCD spectra of different enantiomeric mixtures of R/S-camphor in Nujol mulls were recorded and linear regressions of VCD intensities (ΔAbs.) vs. % ee for selected bands were found. Finally, the VCD intensities of a blind sample were interpolated in these linear regressions, obtaining its % ee with a rms of 2.4. These results in the solid phase were complemented with the determination of % ee in the liquid phase by VCD and NMR techniques, which are proved to be complementary techniques to carry out this kind of analysis. In the same way as in the VCD solid phase, linear regressions of ΔAbs. vs. % ee for selected bands were established, obtaining a rms of 1.1 in the % ee determination of a blind sample. 1H NMR experiments at 600 MHz using the chiral solvating agent, (S,S)-ABTE, allow the determination of the proportions of enantiomers in CD2Cl2solution with great accuracy. 13C CPMAS NMR spectra prove that this technique cannot be used for conglomerates and/or solid solutions.

J. Comput. Chem. 39, 546-556 (2018)

DOI: 10.1002/jcc.25098 (Openaccess)

An interacting quantum atom study of model SN2 reactions (X–···CH3X, X = F, Cl, Br, and I)

The quantum chemical topology method has been used to analyze the energetic profiles in the X + CH3 XCH3 + XSN2 reactions, with X = F, Cl, Br, and I. The evolution of the electron density properties at the BCPs along the reaction coordinate has been analysed. The interacting quantum atoms (IQA) method has been used to evaluate the intra-atomic and interatomic energy variations along the reaction path. The different energetic terms have been examined by the relative energy gradient method and the ANANKE program, which enables automatic and unbiased IQA analysis.

Chem. Phys. Lett. 691, 33-36 (2018)

DOI: 10.1016/j.cplett.2017.10.059

A LFER analysis of the singlet-triplet gap in a series of sixty-six carbenes

Ab initio G4 calculations have been performed to investigate the singlet-triplet gap in a series of 66 simple carbenes. Energies and geometries were analyzed. An additive model has been explored that include four interaction terms. An abnormal behavior of the cyano group has been found. The 13C absolute shieldings of the carbenic carbon atom were calculated at the GIAO/B3LYP/6-311++G(d, p).

J. Mol. Struct. 1155, 205-214 (2018)

DOI: 10.1016/j.molstruc.2017.10.112

Molecular structure in the solid state by X-ray crystallography and SSNMR and in solution by NMR of two 1,4-diazepines

The crystals of two 1,4-diazepines prepared from curcuminoid β-diketones and ethylenediamine were studied by X-ray crystallography and NMR. Their tautomerism, intramolecular hydrogen bonds and conformation were determined.

Coord. Chem. Rev. 339, 153–182 (2017)

DOI: 10.1016/j.ccr.2017.03.011

The organic chemistry of poly(1H-pyrazol-1-yl)methanes

Since their first synthesis by Hückel (1937) and the first systematic exploration by Trofimenko (1970), interest in poly(1H-pyrazol-1-yl)methanes (bis, tris and tetrakis) has increased dramatically. This review focuses on the synthesis and reactivity of these ligands and contains 541 different structures and 269 references. After a brief historical introduction, the synthesis, reactivity, and nature of the coordinated metals are described along with some properties of these compounds, particularly the complete set of X-ray molecular structures. All of the formulae are represented to show the extraordinary richness of poly(1H-pyrazol-1-yl)methanes and to promote the use of the already known poly(1H-pyrazol-1-yl)methanes in coordination chemistry and the design of new ligands with the reported procedures.

J. Mol. Struct. 1137, 186-192 (2017)

DOI: 10.1016/j.molstruc.2017.02.032

The structure of N-arylindazoles and their aza-derivatives in the solid state: A systematic analysis of the Cambridge Structural Database coupled with DFT calculations

A search in the Cambridge Structural Database for N-aryl indazoles and their aza derivatives affords 227 structures (183 1-aryl and 44 2-aryl). To discuss their structures, DFT calculations on 20 model compounds were carried out. The geometry of the five-membered ring (the pyrazole) and the conformation if the N-aryl substituent were analyzed.

Struct. Chem. 28, 345-355 (2017)

DOI: 10.1007/s11224-016-0882-y

An insight on the aromatic changes in closed shell icosagen, tetrel, and pnictogen phenalenyl derivatives

A computational study of the aromatic and antiaromatic characteristics of closed shell charged phenalenyl (PLY+1 and PLY−1) upon replacement of the central carbon atom by icosagen (B, Al and Ga), tetrel (Si and Ge) and pnictogen (N, P and As) atoms comprising systems in which the icosagen and pnictogen derivatives considered are neutral while the tetrel ones are anions or cations, has been carried out at the B3LYP/6–311++G(d,p) computational level. By substitution, two different kinds of structures have been obtained, one planar (N and B) and another one bowl-shaped depending on the size of the central atom. In terms of aromaticity, the substitution of the central C atom causes a loss of the aromatic character in all cases as indicated by nucleus-independent chemical shifts (NICS) profiles and NICS values on the 0.001 au isosurface. Regarding the charge, PLY+1 presents larger electron delocalisation than PLY−1, phenomenon associated with aromaticity. Furthermore, the current density maps for those planar systems corroborate NICS findings, showing anticlockwise currents in PLY+1 (like in benzene) but clockwise in PLY-N0 and PLY-B0, indicating aromatic and antiaromatic behaviour, respectively.

J. Org. Chem., 81, 7612–7625 (2016)

DOI: 10.1021/acs.joc.6b01330

15N NMR Spectroscopy, X-ray and Neutron Diffraction, Quantum-Chemical Calculations, and UV/vis-Spectrophotometric Titrations as Complementary Techniques for the Analysis of Pyridine-Supported Bicyclic Guanidine Superbases

Pyridine substituted with one and two bicyclic guanidine groups has been studied as a potential source of superbases. 2-{hpp}C5H4N (I) and 2,6-{hpp}2C5H3N (II) (hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) were protonated using [HNEt3][BPh4] to afford [I-H][BPh4] (1a), [II-H][BPh4] (2), and [II-H2][BPh4]2 (3). Solution-state 1H and 15N NMR spectroscopy shows a symmetrical cation in 2, indicating a facile proton-exchange process in solution. Solid-state 15N NMR data differentiates between the two groups, indicating a mixed guanidine/guanidinium. X-ray diffraction data are consistent with protonation at the imine nitrogen, confirmed for 1a by single-crystal neutron diffraction. The crystal structure of 1a shows association of two [I-H]+ cations within a cage of [BPh4]− anions. Computational analysis performed in the gas phase and in MeCN solution shows that the free energy barrier to transfer a proton between imino centers in [II-H]+ is 1 order of magnitude lower in MeCN than in the gas phase. The results provide evidence that linking hpp groups with the pyridyl group stabilizes the protonation center, thereby increasing the intrinsic basicity in the gas phase, while the bulk prevents efficient cation solvation, resulting in diminished pKa(MeCN) values. Spectrophotometrically measured pKa values are in excellent agreement with calculated values and confirm that I and II are superbases in solution.

Chem. Commun., 2016, 52, 9656-9659.

DOI: 10.1039/c6cc04350j

On the existence of intramolecular one-electron Be–Be bonds

Although the Be–Be bond is extremely weak in Be2 dimers, we have shown that rather stable Be–Be one-electron sigma bonds are formed upon electron attachment to 1,8-diBeX-naphthalene derivatives. Wavefunction analyses corroborate the formation of Be–Be covalent linkages in which the extra electron is accommodated between the Be atoms as reflected in the dramatic shortening of the Be–Be distance with respect to the corresponding neutral molecule.

Bull. Chem. Soc. Japan, 89, 762-769 (2016)

DOI: 10.1246/bcsj.20160026

The Thermodynamic Stability of Adamantylideneadamantane and Its Proton- and Electron-Exchanges. Comparison with Simple Alkenes

We report herein the results of an experimental and computational study of adamantylideneadamantane (1) and a variety of substituted ethylenic hydrocarbons. The standard enthalpy of formation in the gas phase as well as the gas-phase basicity (GA) of 1were experimentally determined for the first time, respectively by calorimetric techniques and FT-ICR spectrometry. In parallel, computational studies at the MP2/6-311+G(d,p), G3(MP2), and G3 levels were performed on the neutral (1) and protonated (1H+). The agreement with experimental results was very good. The structures of 1 and 1H+ were subject to treatment by “Atoms in Molecules” in order to assess the characteristics of the closest H···H interactions involving both adamantane moieties. Also, the second-order perturbation analysis within the Natural Bond Orbital Theory methodology shows four degenerate charge-transfer interactions between the σ C–H bond of one of the adamantyl subunits towards the σ* C–H of the other adamantyl subunit. The standard enthalpies of formation of new adamantyl compounds were obtained using our experimental data. The computational study of a variety of ethylenic compounds including cyclohexylidenecyclohexane and several alkyl-substituted ethylenes using isodesmic and homodesmotic reactions was carried out. This study was extended to their proton affinities and gas-phase basicities.

Chem. Eur. J. 22, 10651–10660 (2016)

DOI: 10.1002/chem.201600932

Saddle-Shaped Cyclic Indole Tetramers: 3D Electroactive Molecules

We present a joint theoretical and experimental study of a series of cyclic indole tetramers aimed at understanding the fundamental electronic properties of this 3D platform and evaluating its potential in the construction of new semiconductors. To this end, we combined absorption and Raman spectroscopy, cyclic voltammetry, and spectroelectrochemistry with DFT calculations. Our results suggest that this platform can be easily and reversibly oxidized. Additionally, it has a HOMO that matches very well with the workfunction of gold, therefore charge injection from a gold electrode is expected to occur without significant barriers. Interestingly, the cyclic tetraindoles allow for good electron delocalization in spite of their saddle-shaped structures. The steric constraints introduced by N-substitution significantly inhibits ring inversion of the central cyclooctatetraene unit, whereas it only barely affects the optical and electrochemical properties (a slightly higher oxidation potential and a blueshifted absorption upon alkylation are observed).

Tetrahedron 72, 4690-4699 (2016)

DOI: 10.1016/j.tet.2016.06.050

Aromatic changes in isoelectronic derivatives of phenalenyl radicals by central carbon replacement

A computational study of the aromatic characteristics of phenalenyl (PLY) upon replacement of the central carbon atom by Si, Ge, N, P, As, B, Al and Ga atoms comprising isoelectronic series with different charges (0, +1, −1) has been performed at the B3LYP/6-311++G(d,p) level. Two different geometries have been obtained, one planar and another one bowl-shaped. PLY derivatives exhibit a loss of the aromatic character in all cases indicated by NICS (Nucleus-Independent Chemical Shifts) values. These aromatic features are also in agreement with the pyramidalisation undergone by the central atom. The current density maps for those planar systems corroborate NICS findings. These variations in the aromaticity have been rationalised in terms of charge localisation. Harmonic oscillator model of aromaticity (HOMA) and para-delocalisation indices (PDI) have been used to evaluate the electron density delocalisation. HOMA values do not correlate with NICS but PDI indices follow the same trend than NICS.


Chem. Eur. J. 22, 9804-9811 (2016)

DOI: 10.1002/chem.201601201

The Conformational Map of Volatile Anesthetics: Enflurane Revisited

Previous ambiguities in the conformational and structural landscape of the volatile anesthetic enflurane have been solved combining microwave spectroscopy in a jet expansion and ab initio calculations. The broadband (2–18 GHz) rotational spectra identified three different rotamers, sharing a common trans ether skeleton but differing in the ±gauche/trans position of the terminal chlorine atom. For each chlorine conformation two different gauche orientations were predicted for the opposite difluoromethyl group, but only one is experimentally observable due to collisional relaxation in the jet. The experimental dataset comprised nine different isotopologues (35Cl, 37Cl, 13C) and a large number (>6500) of rotational transitions. The inertial data provided structural information using the substitution and effective procedures. The structural preferences were rationalized with additional ab initio, natural-bond-orbital and non-covalent-interaction analysis, which suggest that plausible anomeric effects at the difluoromethyl group could be overridden by other intramolecular effects. The difluoromethyl orientation thus reflects a minimization of inter-fluorine repulsions while maximizing F⋅⋅⋅H attractive interactions. A comparison with previous electron diffraction and spectroscopic data in the gas and condensed phases finally resulted in a comprehensive description of this ether, completing a rotational description of the most common multi-halogenated anesthetics.

Tet. Lett. 57, 1838-1842 (2016)

DOI: 10.1016/j.tetlet.2016.03.044

Theoretical studies on the conformation of large carbocyclic rings. I. 5,6,11,12,17,18-Hexahydrotribenzo[a,e,i]cyclododecane (1,2;5,6;9,10-tribenzododeca-1,5,8-triene)

Tribenzododecatriene is a simple and symmetric molecule that constitutes an excellent model for comparing structural properties both measured and computed. B3LYP/6-311++G(d,p) calculations perfectly reproduced the geometry and NMR properties of this compound in its C2 geometry.

Struc. Chem. 27, 705-730 (2016)

DOI: 10.1007/s11224-015-0704-7

The structure of β-diketones related to curcumin determined by X-ray crystallography, NMR (solution and solid state) and theoretical calculations

Structural data are reported on sixteen ketoenols of β-diketones: solution NMR, solid-state NMR (CPMAS and MAS) and X-ray crystallography (four compounds, where three are new). The emphasis is on the tautomerism between both ketoenols, in solution and in the solid state. GIAO/B3LYP/6-311++G(d,p) and Quantum ESPRESSO (QE) calculations were used and compared. For average values, the GIAO/DMSO-PCM is enough, but splittings can only be approached by using QE. A case of rotational disorder has been analyzed. Some anomalies related to C–F bonds and to the C–CF3 group have been detected.

Struct. Chem. 27, 91-99 (2016)

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Aromaticity of benzenoid hydrocarbons with inserted –B=B– and –BH–BH– groups: a comparison

Structures of selected polycyclic conjugated hydrocarbons with –B=B– and –BH–BH– moieties inserted in different places were calculated at the B3LYP/6-311++G** level and their aromatic properties evaluated. HOMA, NICS(0), NICS(1)zz, Λ and PDI indices were used for studying their aromatic properties. Both optimized planar (as in parent hydrocarbons) and non-planar structures were taken into account. It is shown that insertion of both types of boron groups disturbs and decreases the aromaticity of the corresponding hydrocarbons. The decreasing effect of the –BH–BH– group is much stronger. What is quite intriguing is that it appears that non-planar structures of the studied compounds have a little higher aromaticity than the strictly planar ones. Mutual correlations between results obtained by different aromaticity indices are calculated and thoroughly discussed.

Phys. Chem. Chem. Phys., 17, 14961-14971 (2015)

DOI: 10.1039/C5CP00876J

Influence of fluoro and cyano substituents in the aromatic and antiaromatic characteristics of cyclooctatetraene

An exhaustive and systematic study of the structural and electronic properties of cyclooctatetraene (COT) upon substitution of hydrogen atoms by fluoro and cyano groups has been carried out in order to analyse the influence of both substituents on the aromaticity. We found that C–C distances decrease with fluoro substitution while in cyano derivatives the opposite happens. All the compounds retain their original structural type, with the exception of the cyano derivatives; thus, compounds 25CN6T, 27CN6T and 30CN8T show boat-like structure, whereas compounds 20CN5T,26CN6T, and 29CN7T present twisted structures. Regarding the relative energies of those compounds with the same number of substitutions, it was found that compounds where the X groups were more separated among them were the most stable ones. Inversion barriers (ΔETS) were found to increase with the number of substitutions; in the case of fluoro derivatives these barriers have a two-fold, increase compared to the parent compound while in the cyano ones a three-fold increase was observed. The aromatic character based on the NICS values, was found to increase in the ground singlet states and in the transition states of both fluoro and cyano derivatives. For triplet states, a decrease of the aromatic behaviour was found upon substitution. NICS profiles and 3D NICS isosurfaces confirm such findings. Finally, HOMA indexes corroborate the aromatic changes described by the NICS values, although, no good correlations between both quantities were found.

ChemPhysChem, 16, 465-469 (2015)

DOI: 10.1002/cphc.201402711

Linear Free-Energy Relationships between a Single Gas-Phase Ab Initio Equilibrium Bond Length and Experimental pKa Values in Aqueous Solution

Remarkably simple yet effective linear free energy relationships were discovered between a single ab initio computed bond length in the gas phase and experimental pKa values in aqueous solution. The formation of these relationships is driven by chemical features such as functional groups, meta/para substitution and tautomerism. The high structural content of the ab initio bond length makes a given data set essentially divide itself into high correlation subsets (HCSs). Surprisingly, all molecules in a given high correlation subset share the same conformation in the gas phase. Here we show that accurate pKa values can be predicted from such HCSs. This is achieved within an accuracy of 0.2 pKa units for 5 drug molecules.

ChemPhysChem 15, 3493-3501 (2014)

DOI: 10.1002/cphc.201402442

A Computational Study on 3-Azonia-, 3-Phosphonia-, and 3-Arsoniaspiro[2.2]pentanes and Related Three-Membered Heterocycles

A theoretical study at the ab initio MP2/6-311++G(d,p) level of theory is carried out to characterize several heterocyclic spiro[2.2]pentane cations with N, P, and As as spiro atoms. The strain and relative stability of the spiropentanes are obtained through isodesmic reactions. Nucleus-independent chemical shifts (NICS) and 3D NICS isosurfaces show σ-aromatic characteristics, similar to those found in cyclopropane. The interaction with the Cl anion, which results in four different stationary structures, is studied and characterized by means of the atoms in molecules methodology, and Cl⋅⋅⋅pnicogen, Cl⋅⋅⋅H, and Cl⋅⋅⋅C interactions are found. The most stable structure in all cases corresponds to opening of one of the three-membered rings, due to the attack of the Cl atom, and CCl bond formation. Furthermore, the reaction with the 3-boranuidaspiro[2.2]pentane anion results in the formation of a new compound through cleavage of one ring of both reactants.

Eur. J. Org. Chem. 2014, 5370-5377 (2014)

DOI: 10.1002/ejoc.201402509

Aromaticity and Magnetic Properties of 1- and 2-Indenones and Their Aza Derivatives

The almost unknown series of 1- and 2-indenones and their aza-derivatives have been analyzed with the aim of understanding the higher stability and aromaticity of the 1-one compared to the 2-one series. The effect of tetrafluorination of the six-membered ring on their relative stability and aromaticity and the corresponding 19F–19F spin–spin coupling constants (SSCC) have been analyzed for the compounds of these two series. Magnetic NICS and electronic PDI, FLU, and MCI aromaticity criteria, complemented by an energy decomposition analysis, allow the higher stability and aromaticity of 1-indenones compared with 2-indenones to be attributed to the π-component of the orbital interaction term. The reduced aromatic character of the 2-one series also provides an explanation for the 19F–19F SSCC observed in the tetrafluorinated 2-one compounds, which differ significantly from those of 1,2,3,4-tetrafluorobenzene.

Helv. Chim. Acta 97, 471-490 (2014)

DOI: 10.1002/hlca.201300395

A Spectroscopic Study of Colchicine in the Solid State and in Solution by Multinuclear Magnetic Resonance and Vibrational Circular Dichroism

Although almost 200-years-old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density-functional theory (DFT) studies of geometry, energy, and NMR; 1H-, 13C-, and 15N-NMR chemical shifts and some spin-spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid-state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms.

Organometallics, 33, 616–619 (2014)

DOI: 10.1021/om401215m

Arene–Ruthenium Chemistry and Brønsted Acid Catalysis of a Chiral Phosphane-Hydroxyl Ligand

The phosphane-hydroxyl ligand (SC1,RC2)-Ph2PC(Ph)HC(OH)HCH2OMe (POH) displays κ1P, κ2P,O, κ3P,O,O′, and anionic deprotonated κ3P,O,O′ coordination modes toward the metallic (η6-p-MeC6H4iPr)Ru moiety. The hydroxyl group in [(η6-p-MeC6H4iPr)Ru(κ3P,O,O′-POH)][SbF6]2(3) has strong acidic properties. This complex catalyzes the Diels–Alder reaction between cyclopentadiene and trans-β-nitrostyrene or methacrolein as well as the Friedel–Crafts reaction between indole and methyl 3,3,3,-trifluoropyruvate or trans-β-nitrostyrene. Solution studies strongly indicate that complex 3 acts as a metallic Lewis acid assisted Brønsted-acid catalyst.

ARKIVOC, ii, 319-332 (2014)

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Preparation of 2,2-dimethylchroman-4-ones from 5-alkyl-substituted resorcinols: microwave-assisted synthesis and theoretical calculations

The influence of different 5-alkyl-substituted resorcinols on the formation of 2,2-dimethyl-chroman-4-ones is examined experimentally and theoretically. Structures are fully assigned by means of experimental and theoretical 13C and 1H NMR chemical shifts. Based on experimental and theoretical calculations of Friedel-Crafts acylation, it is possible to explain the formation of 2,2-dimethyl-5-hydroxychroman-4-ones and/or 2,2-dimethyl-7-hydroxychroman-4-ones. Evaluation of their biological activity as cannabinoid receptor ligands is also reported. 

J. Phys. Org. Chem. 2013, 26 791–796

DOI: 10.1002/poc.3159

Relationship between experimental pKa values in aqueous solution and a gas phase bond length in bicyclo[2.2.2]octane and cubane carboxylic acids

Linear correlations were established between the calculated bond lengths and the pKa or σI values for a series of 4-substituted bicyclo[2.2.2]octane-1-carboxylic acid and 4-cubane-1-carboxylic acid derivatives. The bond lengths have been calculated at a modest computational level, HF/6-31G(d), both in the gas phase and with the continuum solvation model, polarisable continuum model (PCM). In general, the best correlations are obtained when the PCM model is taken into account, especially when neutral and charged molecules are considered together. The best models in each case show square correlation coefficients (R2) larger than 0.9 and indicate that they can be used as predictive tools. These results expand previous results that indicate the possibility of a relationship between gas phase bond length and pKa values in aqueous solution and indicate that such relationships are more general than hitherto expected. 

Cent. Eur. J. Chem. 11, 1711-1722 (2013)

DOI: 10.2478/s11532-013-0311-7

A theoretical study of the limits of the acidity of carbon acids in phase transfer catalysis in water and in liquid ammonia

The acidities of a large number of carbon acids have been theoretically calculated for the gas-phase and for DMSO solution. The gas-phase values, both ΔH and ΔG, are very well correlated with the available experimental data. From the calculated ΔG values in DMSO and the pKas in the same solvent, a homogeneous set of pKa (DMSO) values was devised that was used to generate pKa(water). These last pKas were used to establish the limits of the acidity of carbon acids for reactions under PTC conditions both alkylations and H/D exchange. A step further led to the pK as in liquid ammonia and from them to the virtual use of PTC using liquid ammonia instead of water.

Phys. Chem. Chem. Phys. 15, 14026-14036 (2013)

DOI: 10.1039/C3CP51963E

Modeling the mechanism of glycosylation reactions between ethanol, 1,2-ethanediol and methoxymethanol

The mechanism of the SN2 model glycosylation reaction between ethanol, 1,2-ethanediol and methoxymethanol has been studied theoretically at the B3LYP/6-311+G(d,p) computational level. Three different types of reactions have been explored: (i) the exchange of hydroxyl groups between these model systems; (ii) the basic catalysis reactions by combination of the substrates as glycosyl donors (neutral species) and acceptors (enolate species); and (iii) the effect on the reaction profile of an explicit H2O molecule in the reactions considered in (ii). The reaction force, the electronic chemical potential and the reaction electronic flux have been characterized for the reaction path in each case. Energy calculations show that methoxymethanol is the worst glycosyl donor model among the ones studied here, while 1,2-ethanediol is the best, having the lowest activation barrier of 74.7 kJ mol−1 for the reaction between this one and the ethanolate as the glycosyl acceptor model. In general, the presence of direct interactions between the atoms involved in the penta-coordinated TS increases the activation energies of the processes.

Struct. Chem. 24, 542-548 (2013)


HOMA parameters for the boron–boron bond: How the introduction of a BB bond influences the aromaticity of selected hydrocarbons

An extension of the harmonic oscillator model of aromaticity (HOMA) model for systems with boron–boron bonds is presented. For the first time, the parameters of the HOMA model are estimated using only theoretically calculated bond lengths. The HOMA parameters obtained make geometric aromaticity studies possible for a large number of compounds containing the boron–boron bond. The derived HOMA parameters have been used to investigate how the introduction of the boron–boron moiety in the structure of selected hydrocarbons modifies their aromaticity. The conclusion is that the insertion of a boron–boron bond usually strongly decreases the aromaticity of the boron-containing compounds in comparison to their parent hydrocarbons.

Chem. Eur. J. 18, 13379–13387 (2012)


Regioselectivity in the intramolecular heck reaction of a series of cyclic sulfonamides: an experimental and computational study.

Regioselectivity in the intramolecular Heck reaction of a series of N-sulfonyl-2,5-dihydro-3-substituted pyrroles was studied. These substrates are unbiased in terms of the formed ring size of the new heterocycle. Results indicate that high levels of regioselectivity are observed under a range of conditions, and that there is an underlying propensity for carbon-carbon bond formation at the most hindered end of the alkene. For two examples (3-Me and 3-tBu), DFT calculations were performed and indicate that in both cases, the modelled transition state for carbopalladation is energetically lower for the experimentally preferred isomer.

J. Mol. Struct., 1015,138-146 (2012)


The tautomeric structures of 3(5),3′(5′)-azopyrazole [(E)-1,2-di(1H-pyrazol-3(5)-yl)diazene)]: The combined use of NMR and electronic spectroscopies with DFT calculations

An azo derivative of 1H-pyrazole has been chosen to study the information obtained from different techniques for determining the structure of a non-crystalline compound in the solid-state and in solution. Syn–antiisomerism of the azo group, prototropic tautomerism of the 1H-pyrazole and rotation about the pyrazole–azo group resulted in 20 structures that were analyzed. Energy calculations, 13C and 15N chemical shifts, 1H–1H coupling constants and electronic spectra reduced the 20 possible structures to only one, the 3,3′-Z,Z-anti-azopyrazole.

Struct. Chem. 23, 595-600 (2012)

DOI: 10.1007/s11224-011-9907-8

Calculation of the HOMA model parameters for the carbon-boron bond

An extension of the harmonic oscillator model of aromaticity (HOMA) model to systems with carbon–boron bonds is presented. Model parameters were estimated using experimental and theoretical bond lengths. It is shown that both approaches produce very similar HOMA models. In the second part of the article, the aromaticity levels of several model compounds containing carbon–boron bonds are calculated using the previously obtained parameters. The results of these calculations are compared with those provided by other aromaticity indices. The aromaticity of boron-containing compounds is also compared with the aromaticity of analogous compounds containing carbon and nitrogen.

Struct. Chem. 23, 1245-1252 (2012)

DOI: 10.1007/s11224-012-9991-4

A theoretical study of six-membered rings containing the -N=S-S=N- motif

The sulfur electronic structure allows for the existence of hypervalent molecules that were discussed as early as 1939 by Schomaker and Pauling. In the present paper, we report a theoretical study of three hypothetical possible six-membered rings that contain the –N=S–S=N– motif carried out at the MP2/aug-cc-pVDZ level. Three minima have been found, of which two of them are six-membered rings with all covalent bonds. Since they do not have a planar structure, we have calculated the aromaticity index NICS through the symmetry axis perpendicular to the mid-plane and at various points in space. Benzene, cyclohexane, and 1,2,5-thiadiazole have served as points of comparison.

Phys. Chem. Chem. Phys. 14, 11468-11477 (2012)

DOI: 10.1039/C2CP41230F

Strong interactions between copper halides and unsaturated systems: new metallocycles? Or the importance of deformation

The complexes formed by CuF with CC double and triple bonds have been studied at the MP2 and CCSD(T) computational levels. The interaction of CuF with acetylene, ethylene and their fluoro derivatives is very strong, with interaction energies close to those of conventional covalent bonds. Hence, these complexes could be actually viewed as a new kind of metallocycles, with significantly strong Cu–C linkages. All electronic indexes analyzed by means of the AIM, ELF and NBO formalisms, indicate that the strength of the interaction should increase with the number of fluorine substituents in both series of compounds. Surprisingly, however, although both series of compounds exhibit the same bonding arrangements, they follow opposite stability trends and the expected increase of the interaction energies with the number of fluorine substituents is only observed in the acetylene series. The reason for this unexpected behavior is once more associated with the effects triggered by the distortion of the interacting subunits. Deformation not only has a direct energetic cost but dramatically affects the intrinsic properties of the interacting systems.

J. Phys. Chem. A 116, 8250-8259 (2012)

DOI: 10.1021/jp304495f

Mechanisms of Formation of Hemiacetals: Intrinsic Reactivity Analysis

The reaction mechanism of the hemiacetal formation from formaldehyde and methanol has been studied theoretically at the B3LYP/6-311++G(d,p) level. In addition to the study of the reaction between the isolated reactants, three different kinds of catalysis have been explored. The first one examines the use of assistants, especially bridging water molecules, in the proton transfer process. The second one attempts to increase the local electrophilicity of the carbon atom in formaldehyde with the presence of a Brønsted acid (H+ or H3O+). The last one considers the combined effect of both catalytic strategies. The reaction force, the electronic chemical potential, and the reaction electronic flux have been characterized for the reaction path in each case. In general, it has been found that structural rearrangements represent an important energetic penalty during the activation process. The barriers for the reactions catalyzed by Brønsted acids show a high percentage of electronic reorganization contribution. The catalytic effects for the reactions assisted by water molecules are due to a reduction of the strain in the transition state structures. The reaction that includes both acid catalysis and proton assistance transfer shows the lowest energy barrier (25.0 kJ mol–1).

Tetrahedron 67, 7316-7320 (2011)


Isomerization barriers in bis(4H-thiopyran) and in bothioxanthenes

The inversion and rotation mechanisms for the isomerization of Feringa’s bithioxanthenes existing in two conformations, up/up and up/down, have been calculated at the B3LYP/6-31G(d) and B3LYP/6-311++G(d,p) levels. The inversion mechanism that maintains the double bond nature of the central bond is a classical one but the rotation mechanisms that break the double bond to form a biradical needs to explore the singlet and triplet states. To do this we have removed the four fused phenyl rings of bithioxanthene and calculated at the CASSCF and CASPT2 levels bis(4H-thiopyran) proving that B3LYP calculations yield reasonable results for the rotation barriers.

J. Phys. Org. Chem. 24, 744-750 (2011)

DOI: 10.1002/poc.1813

Thermodynamic and kinetic effects of Lewis acid complexation on a Schiff base present in two tautomeric forms

The effect of complexation with Lewis acids on the tautomeric equilibrium of a derivative of pyridoxal has been explored using density functional theory. Three complexation sites (pyridine nitrogen, aromatic ring, and carbonyl group) have been considered. The tautomeric equilibrium can be modulated with the formation of complexes at the different sites. The changes observed in the geometric, energetic and electronic properties of the tautomers and transition states have been analyzed. Relationships have been found between those parameters, including a relationship between energetic and geometric parameters in agreement with the Hammond postulate.

Struct. Chem. 22, 707-715 (2011)

DOI: 10.1007/s11224-011-9749-4

Modeling the allosteric effect: modification of the tautomerism by intermolecular interactions and extension to molecular wires

B3LYP/6−31G(d) and B3LYP/6−311++G(d,p) calculations were carried out on quinolone and its four azaderivatives (15 tautomers), five wire models (10 tautomers) for proton transfer formed of anthracenol and azaacridines and the corresponding five crown ethers (ten tautomers) in the anthracenol part. The wires are formed by four carbon atoms existing either as cumulenes (pentaene) or polyynes (diyne). On these structures the effect of hydrogen bonds with HF as hydrogen bond donor, protonation on the aza N atoms and coordination with Li+ on the same positions were studied. The resulting energies were analyzed taking into account proximity effects.

Comp. Theor. Chem. 966, 334-339 (2011)

DOI: 10.1016/j.comptc.2011.03.034

A theoretical study of the conformation, basicity and NMR properties of 2,2'-, 3,3'- and 4,4'-bipyridines and their conjugated acids

A theoretical study at the B3LYP/6-311++G(d,p) level has been carried out on 2,2′-, 3,3′- and 4,4′-bipyridines, as well as on their monoprotonated and diprotonated forms. The geometries, torsion angles, and the energies of the minima and transition states have been calculated with good agreement with previous calculations and with most of the scarce available data. The absolute shieldings were calculated on these geometries using the GIAO approximation and transformed into chemical shifts using previously established relationships.

Inorg. Chem. 50, 4212-4220 (2011)

DOI: 10.1021/ic102314r

Unprecedented 1,3-Diaza[3]ferrocenophane Scaffold as Molecular Probe for Anions

The guanidine unit in the guise of 2-aminoimidazole in the new structural motif 2-arylamino-1,3-diaza[3]ferrocenophane 4 acts as a binding site for anions. The electrochemical behavior of this compound has been studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) and was found to exhibit a quasi reversible oxidation peak, associated to the Fe(II)/Fe(III) redox couple (Ep = 440 mV), and a non-reversible oxidation wave (Ep = 817 mV), probably associated to the oxidation of the C═N unit present in the guanidine bridge. Recognition of AcO, PhCO2, F, Cl, and Br anions by the free receptor and the less basic anions Br, Cl, and NO3 by its monoprotonated form takes place by unusual redox-ratiometric measurements and spectroscopic (1H NMR and UV−vis) changes.

Chem. Phys. Lett. 515, 210-213 (2011)

DOI: 10.1016/j.cplett.2011.09.037

Multiple 3c-2e bonding of methane with metal cations

Methane is a greenhouse gas but at the same time a possible starting material in chemical industry. Here, we demonstrate by computational methods that methane could form in gas phase stable adducts with alkaline and earth alkaline metal cations. The interaction can be described as multiple 3c─2e bonding between a cation and C─H bonds. In the alkaline metal adducts the open mode prevails, while for the earth alkaline moieties it is difficult to define, whether there is either close or open mode prevailing.

Comput. Theor. Chem. 974, 37-42 (2011)


A theoretical study of the conformation of 2,2’-bifuran,2,2’-bithiophene, 2,2’-bitellurophene and mixed derivates: chalcogen-chalcogen interactions or dipole-dipole effects.

Using as models 2,2′-biheterocycles (furan, thiophene, selenophene, tellurophene) the possibility of stabilizing effects due to the proximity of two chalcogen atoms (O, S, Se, Te) was explored. The geometries of the ground states were compared satisfactorily with the available experimental results. The torsional barriers through planar and orthogonal transition states were calculated and discussed in function of the nature of the chalcogen atoms. Special attention was devoted to dipole moments that were calculated by a vector summation with good results

Chem. Eur. J. 16, 11897-11905 (2010)

DOI: 10.1002/chem.201001254

New Insights into Factors Influencing B N Bonding in X:BH3-nFn and X:BH3-nCln for X=N2, HCN, LiCN, H2CNH, NF3, NH3 and n=0-3: The Importance of Deformation

Understanding the bonding in complexes X:BH3−nFn and X:BH3−nCln, for X=N2, HCN, LiCN, H2CNH, NF3, NH3 with n=0–3, is a challenging task. The trends in calculated binding energies cannot be explained in terms of any of the usual indexes, including π donation from the halogen lone pairs to the p(π) empty orbital on B, deformation energies, charge capacities, or LUMO energies, which are normally invoked to explain the higher Lewis acidity of BCl3 relative to BF3. The results of the high-level G3B3 ab initio calculations reported in this study suggest that the interaction energies of these complexes are determined by a combination of at least three factors. These include the decrease in the electron-accepting ability of B as a result of π donation by the halogen atom, the increase in the electron-acceptor capacity of B due to deformation of the acid, and the large increase in the deformation energy of the acid with increasing halogen substitution. The dominant effects are those derived from the electronic effects of acid deformation. Deformation not only has direct energetic consequences, which are reflected in the large differences between dissociation (D0) and interaction (Eint) energies, but also leads to an enhancement of the intrinsic acidities of BH3−nFn and BH3−nCln moieties by lowering the LUMO energies to very different extents, consistent with the frontier orbital model of chemical reactivity. Although this lowering depends on both the number and the nature of the halogen substituents, binding energies do not systematically increase or decrease as the number of halogen atoms increases.

J. Am. Chem. Soc. 132, 7862-7863 (2010)

DOI: 10.1021/ja1025062

Crystallization of an Achiral Cyclohexanone Ethylene Ketal in Enantiomorphs and Determination of the Absolute Structure

The achiral 4-methoxy-4-(p-methoxyphenyl)-cyclohexanone ethylene ketal (1) resolves spontaneously. The crystal structure is solved in chiral spatial group P2(1). Because compound 1 is composed of only light atoms (C, H, O) it is not possible to determine its absolute structure configuration. An efficient procedure for the absolute structure configuration determination of flexible molecules containing only light atoms is proposed, based on the combination of X-ray diffraction, solid-state VCD, and DFT calculations.

J. Phys. Org. Chem. 23, 526-535 (2010)

DOI: 10.1002/poc.1636

Double proton transfer in crystals of 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a] pyrimidine (hppH): 13C and 15N CPMAS NMR study of (hppH)2

In this paper, we report an example of intermolecular solid-state proton transfer in the bicyclic guanidine, hppH. A combination of X-ray crystallography, CPMAS NMR (13C and 15N) and theoretical calculations allows us to determine that a double proton transfer takes place in the (hppH)2 dimer with an activation energy of about 50 kJ mol−1. According to the B3LYP/6-311++G(d,p) calculations, the double proton transfer occurs non-symmetrically through a zwitterion.

Phys. Chem. Chem. Phys. 12, 5101-5108 (2010)

DOI: 10.1039/b924322d

On the electronic structure and stability of icosahedral r-X2Z10H12 and Z12H122- clusters; r = {ortho, meta, para}, X = {C, Si}, Z = {B, Al}

We report on the electronic structure of the 12-vertexicosahedralclustersr-X2Z10H12and Z12H122–, where X = {C,Si} and Z = {B,Al}. The least stablecluster—with the lowest HOMO–LUMO gap (Eg)—corresponds to theortho-X2Z10H12isomers for all values of X = {C,Si} and Z = {B,Al}. The well-known energetic orderE(para)<E(meta)<E(ortho)forr-carboranes is also valid for all compounds exceptr-C2Al10H12. Substitution of two atoms ofcarbonorsiliconinto theicosahedralcage B12H122−enhances considerably the stability of the system as analyzed fromEggaps, as opposite to Al12H122−, where similar gaps are found upon doublecarbonorsiliconsubstitution regardless of the positions in the cage. In order to highlight similarities and differences in the titleclusters, topological analysis of the electron density was performed, together with analysis of the deviation from polyhedronicosahedralform with (i) volumes, skewness and kurtosis calculations; and (ii) continuous shape measures.

J. Mol. Stuct. 969, 106-110 (2010)

DOI: 10.1016/j.molstruc.2010.01.049

The solid-state structure of primary fatty amines: True amines or ammonium amides?

A computational and experimental NMR study of octadecylamine and hexadecylamine proves that these compounds behave in the solid-state like all other primary amines and not as ammonium amide inner salts.

J. Chem. Inf. Model. 50, 87-96 (2010)

DOI: 10.1021/ci900396k

Prediction of the Basicities of Pyridines in the Gas Phase and in Aqueous Solution

The basicities of 125 pyridine derivatives in the gas phase and in water have been correlated with the electron density properties within the framework of quantum topological molecular similarity (QTMS). We used the theory of quantum chemical topology (QCT) to provide ab initio descriptors that are able to predict pKb values. Partial least squares (PLS) and the machine-learning technique Kriging generated validated models. Properties were considered for systems in their neutral and protonated forms. The compounds were divided into a training set, used to develop the models, and a test set, for which the predicted values of the different models were compared with the experimental ones. The results were found to be good for those compounds with substituents in the meta and para positions, whereas the use of Kriging was required to obtain reasonable results when ortho derivatives were included. The basicity was found to be better described in the gas phase than in water. Special attention was paid to external validation.

J. Chem. Theory Comput. 5, 2763-2771 (2009)

DOI: 10.1021/ct900364y

Beryllium Bonds, Do They Exist?

The complexes between BeX2 (X = H, F, Cl, OH) with different Lewis bases have been investigated through the use of B3LYP, MP2, and CCSD(T) approaches. This theoretical survey showed that these complexes are stabilized through the interaction between the Be atom and the basic center of the base, which are characterized by electron densities at the corresponding bond critical points larger than those found in conventional hydrogen bonds (HBs). Actually, all bonding indices indicate that, although these interactions that we named “beryllium bonds” are in general significantly stronger than HBs, they share many common features. Both interactions have a dominant electrostatic character but also some covalent contributions associated with a non-negligible electron transfer between the interacting subunits. This electron transfer, which in HBs takes place from the HB acceptor lone-pairs toward the σYH* antibonding orbital of the HB donor, in beryllium bonds goes from the lone pairs of the Lewis base toward the empty p orbital of Be and the σBeX* antibonding orbital. Accordingly, a significant distortion of the BeX2 subunit, which in the complex becomes nonlinear, takes place. Concomitantly, a significant red-shifting of the X−Be−X antisymmetric stretching frequencies and a significant lengthening of the X−Be bonds occur. The presence of the beryllium bond results in a significant blue-shifting of the X−Be−X symmetric stretch.

Croat. Chem. Acta 82, 173-183 (2009)

Barriers about Double Carbon-Nitrogen Bond in Imine Derivatives (Aldimines, Oximes, Hydrazones, Azines)

The paper presents the results referring to the inversion mechanism of imines and their derivatives (hydrazones, oximes, azines). The calculated barriers [B3LYP/6-311++G(d,p) and G3B3)] are in good agreement with the scarce existing data. The transition states correspond in all cases to a pure nitrogen inversion except in the case of azines where they have some rotation character. The electron properties of the minima and the transition states have been characterized, allowing explanation of the geometrical changes observed in the process.

Theochem, 896, 92-95 (2009)

DOI: 10.1016/j.theochem.2008.11.005

Does 7-norcaranone (bicyclo[4.1.0]heptan-7-one) exist?

Theoretical calculations have been carried on four compounds, bicyclo[4.1.0]heptan-7-one cis and trans, 2-cyclohepten-1-one and cycloheptenyl cation to determine their UV, IR and NMR spectra (chemical shifts). In the case of the known 2-cyclohepten-1-one the agreement is satisfactory. Predictive properties have been calculated for the elusive bicyclo[4.1.0]heptan-7-one cis molecule.


Tetrahedron 64, 8089-8094 (2008)

Doi: 10.1016/j.tet.2008.06.065

A study of the tautomerism of β-dicarbonyl compounds with special emphasis on curcuminoids

Six β-diketones related to curcumin and curcumin itself have been studied by 13C NMR spectroscopy in chloroform in order to determine the equilibrium constant between the two keto/enol tautomers. In order to do this GIAO/B3LYP/6-31G∗∗ calculations of absolute shieldings (σ, ppm) were carried out. To establish relationships between σ and experimental chemical shifts (δ, ppm), three simple β-diketones (acetylacetone, dibenzoylmethane and benzoylacetone) have been studied. The preference for different groups to be conjugated with the C═O has been determined.

J. Mol. Struct. 891, 325-328 (2008)

Doi: 10.1016/j.molstruc.2008.04.002

Desmotropy in reduced plumbagins: alpha- and beta-Dihydroplumbagins

A report of 1933 about the desmotropy of dihydroplumbagin was examined using both DFT calculations and high field NMR experiments. It was concluded that the report was essentially correct because both tautomers were isolated and characterized.

Struct. Chem. 19, 339-352 (2008)

Doi: 10.1007/s11224-008-9290-2

Substitution effects on neutral and protonated pyridine derivatives along the periodic table

A theoretical study of the monosubstitution effects of all atoms of the second and third rows of the periodic table on the α, β and γ positions of neutral and protonated pyridine has been carried out by means of B3LYP/6-31 + G(d,p) DFT calculations. The geometric and electronic properties, calculated using the Atoms in Molecules methodology, and the electrostatic potential have been analysed. Concurrently, three separate aromaticity indexes (NICS(0), NICS(1) and HOMA) have been evaluated and compared to the above results. Furthermore, the effect of protonation on these parameters has been investigated. A comparison with analogous results for benzene derivatives has also been carried out.

Russ. J. Gen. Chem. 78, 784-792 (2008)

Doi: 10.1134/S1070363208040385

Acid Properties of Porphyrins and Related Systems

Structural, energetic, and electronic aspects of a series of porphyrins and related compounds in their neutral, anion, and dianion electronic states have been studied by means of DFT calculations [B3LYP/6-31+G(d,p)]. Analysis of the electron density puts forward a number of different kinds of interactions between the inner atoms. Intramolecular correlations similar to those found in intermolecular N-H···N interactions have been found.

J. Phys. Org. Chem. 21, 381-386 (2008)

Doi: 10.1002/poc.1350

Theoretical study of racemization in chiral alkenylidene truxenes

DFT based methods have been used to study the racemization process of chiral truxene derivatives. Four minima and the transition state connecting them have been characterized. It has been found that the energetic results for the transition states are correlated for each compound and also among the different systems considered. Thus, a unique equation has been found to fit all the values obtained. Model systems have shown that the calculated barriers are not inherent to the truxene structure. The AIM analysis has shown the presence of a large number of intramolecular closed-shell interactions while electron density and Laplacian at the bond critical points are exponentially correlated with the interatomic distance. 

Arkivoc vii, 48-56 (2008)

Computational studies of the structure of aldazines and ketazines. Part 1. Simple compounds

The molecular structure of seven simple aliphatic and aromatic aldazines and ketazines has been calculated at the B3LYP/6-311++G** computational level. Geometries,  E/Z- isomerism and conformation of the compounds have been compared with the available data (electron diffraction, X-ray crystallography). IR and Raman spectra have been calculated and compared with experimental ones. 

Theochem, 847, 25-31 (2007)

Doi: 10.1016/j.theochem.2007.08.026

Computational studies of the structure of aldazines and ketazines: Part 2. Halogen and alpha,beta-unsaturated derivatives

Nine azines bearing F, Cl, Br, CF3, CF2CF3, CH(CF3)2, CH─CH═CH2, CH─CH═CH(CH3) and CH─CH═CH(C6H5) substituents have been theoretically studied at the B3LYP/6-311++G(d,p) level. Concerning the E/Z isomerism, in all cases, the large groups prefer to be “outside” (in general, E), i.e. for conjugated azines the extended conformation (EEEE) is always preferred. In the case of the CH(CF3)2 substituent, the imine–enamine tautomerism has been studied, the imine one being clearly more stable. The differences in energy between the different isomers and conformers have been statistically analyzed.

Int. J. Mass Spectr., 267, 302-307 (2007)

Doi: 10.1016/j.ijms.2007.02.056

The intrinsic (gas-phase) acidities of bridgehead alcohols. An experimental (FT-ICR) and computational study

The gas-phase acidities of 1-adamantanol and perfluoro1-adamantanol were determined by means of Fourier transform ion cyclotron resonance spectrometry (FT-ICR). The acidity of perfluoro1-adamantanol seems to be the highest ever reported for an alcohol. A computational study of these species and their anions at both the MP2/6-311 + G(d,p) and B3LYP/6-311 + G(d,p) levels was performed. Also studied were the tertiary alcohols (including their perfluorinated forms) derived from norbornane, bicyclo[2.2.2]octane and cubane. It was found that: (i) the intrinsic acidity of non-fluorinated bridgehead alcohols increases with the strain of the hydrocarbon framework and, (ii) perfluorination of these compounds strongly increases their acidity and, likely, significantly modifies their internal strain.

Theor. Chem. Acc. 118, 533-539 (2007)

Doi: 10.1007/s00214-007-0340-4

Theoretical study of neutral and protonated triple bonded molecules formed between C, N, Si, P, B and Al

A theoretical study of the possible protonation sites of simple molecules formed by C, N, Si, P, B and Al that present a triple bond between those atoms has been carried out. The calculations performed include MP2 and CCSD(T) methods with the aug-cc-pVTZ basis set. The nature of the protonated species has been analyzed with the Atoms In Molecules methodology.

Phys. Chem. Chem. Phys. 9, 3970-3977 (2007)

Doi: 10.1039/b702480k

Unusual substituent effects on the bonding of iminoboranes

Substituent effects on iminoboranes XBNH, HBNX and XBNX (X = H, CH3, NH2, OH, F) have been analyzed in the framework of the NBO, AIM and ELF approaches, using B3LYP/6-311++G(d,p) optimized geometries and electron densities. Boron-substituted derivatives, XBNH, are more stable than the corresponding nitrogen-substituted isomers HBNX, with the energy difference increasing as the electron withdrawing character of the substituent increases. The BN linkage is not much affected by N-substitution, but it is significantly altered when the substituent is attached to the boron atom in both XBNH and XBNX series of compounds. Moreover, substituent effects on the structures of iminoboranes are opposite those observed for the corresponding isoelectronic acetylene derivatives. The ELF analysis indicates that electron-withdrawing substituents enhance the localization of electrons in a torus around the CC or the BN axis. As a result, although electron density is depleted at the bcp, the bond does not necessarily become weaker, since density increases around the periphery, a phenomenon named the “hole” effect. The dissimilarities between acetylene and iminoborane derivatives are primarily a consequence of the significant distortion of this torus in the latter, due to the large difference between the electronegativities of B and N, which leads to a large contribution of the resonance structure in some cases. The “hole” effect is reflected in a reasonable correlation between the Laplacian of the electron density at the bcp and the BN bond length.

Dalton Trans, 3995-399 (2007)

Doi: 10.1039/b705703b

A theoretical and experimental study of the fluxional behaviour of molybdenum dihydrobis- and hydrotris-pyrazolylborates

The fluxional barrier of (dicarbonyl)[dihydrobis(3,5-dimethylpyrazol-1-yl)borato][η-(1,2,3)-2-methylpropen-1-yl]-molybdenum (1) has been measured and a complete assignment of its 1H,13C and 15N NMR signals has been carried out. Theoretical calculations at the B3LYP/LANL2DZ level including GIAO absolute shieldings (σ) have allowed to analyze the molecular contributions to the barrier as well as to assign some signals involved in the fluxional process.

Organomet. 25, 5638-5647 (2006)

Doi: 10.1021/om0608197

On the Existence of a-Agostic Bonds: Bonding Analyses of Titanium Alkyl Complexes

The main characteristics of the so-called “agostic bonding” in titanium complexes were computationally investigated in terms of diverse analyses, including the quantum theory of atoms in molecules (QTAIM) and the electron localization function (ELF). Computations on a set of titanium-based molecular models that were presumably able to present α- and β-like bonding showed a clear distinction between α- and β-bonding schemes. In view of the geometric, energetic, and electronic data of these molecules, we concluded that the geometries presenting a Ti···H approximation similar to α bonding are not the result of a bonding attraction. On the contrary, their origin arises from a short-range repulsion between the metal core and the lone pairs of the alkylidene group, the latter pivoting in its own plane around carbon and thereby allowing simultaneously a closer approach between the Ti and the C atoms and indirectly resulting in a short Ti···H distance. Additionally, we found that the electronic and geometric distortion of the C−H bond present in the agostic bonding are not univocally linked to this kind of bonding; instead, this originates in the close distance of the C−H bond and any metal center, independently of whether it is due to an agostic bond or not. Therefore, the lengthening of the C−H bond and the reduction of its electron density at the bond critical point should not be considered as indication of agostic bonding but as a side effect.

Chem. Phys. Lett. 429, 23-26 (2006)

Doi: 10.1016/j.cplett.2006.08.012

The structure of protonated HCP: A classical or non-classical ion?

The bond dissociation enthalpies in n-silanes and n-germanes have been studied with the G2MP2 and G3B3 computational methods. The results have been compared with those of the corresponding n-alkanes. The differences observed in the three families of compounds have been rationalized using the calculated hyperpolarization effect in each family. In addition, the conformational profiles of X2H6 molecules, X = C, Si, and Ge, have been compared.

Chem. Phys. Lett. 429, 58-61 (2006)

Doi: 10.1016/j.cplett.2006.07.098

Theoretical study of the bond energy in n-silanes and n-germanes: Comparison with n-alkanes

The bond dissociation enthalpies in n-silanes and n-germanes have been studied with the G2MP2 and G3B3 computational methods. The results have been compared with those of the corresponding n-alkanes. The differences observed in the three families of compounds have been rationalized using the calculated hyperpolarization effect in each family. In addition, the conformational profiles of X2H6 molecules, X = C, Si, and Ge, have been compared.

Chem. Phys. Lett. 425, 221-224 (2006)

Doi: 10.1016/j.cplett.2006.05.050

The carbon-carbon bond dissociation energy as a function of the chain length

All the C–C fragmentations of the linear n-alkanes, CnH2n+2, for n = 2 to n = 10 and the final C–H bond breaking have been calculated with the composite methods G2, G2MP2, G3, G3MP2B3 and G3B3. The results have been compared with the available experimental data.

Org. Biomol. Chem., 3 , 3905-3910 (2005)

Doi: 10.1039/b510535h

3-(2-Pyridyl)-[1,2,3]triazolo[1,5-a]pyridines. An experimental and theoretical (DFT) study of the ring-chain isomerization 

An experimental (1H NMR) and theoretical (DFT) study of the ring–chain–ring isomerization of 3-(2-pyridyl)-[1,2,3]triazolo[1,5-a]pyrid-7-yl derivatives (A) into 6-{[1,2,3]triazolo[1,5-a]pyrid-3-yl}-2-pyridyl derivatives (B) has been carried out. Based on the calculations, a mechanism of several steps will be proposed. The experimental results as well as the calculations lead to the conclusion that the A–B ratio depends on the electronic properties of the substituents.

J. Phys. Chem. A, 109, 4359-4365 (2005)

Doi: 10.1021/jp050857o

Periodic Trends in Bond Dissociation Energies. A Theoretical Study

Bond dissociation energies (BDEs) of all possible A−X single bonds involving the first- and second-row atoms, from Li to Cl, where the free valences are saturated by hydrogens, have been estimated through the use of the G3-theory and at the B3LYP/6-311+G(3df,2pd)//B3LYP/6-31G(2df,p) DFT level of theory. BDEs exhibit a periodical behavior. The A−X (A = Li, Be, B, Na, Mg, Al, and Si) BDEs show a steady increase along the first and the second row of the periodic table as a function of the atomic number Z(X). For A−X bonds involving electronegative atoms (A = C, N, O, F, P, S, and Cl) the bond energies achieve a maximum around Z(X) = 5. The same behavior is observed when BDEs are plotted against the electronegativity χ(X) of the atom X. Thus, for A−X bonds (A = Li, Be, B, Na, Mg, Al, Si), the BDEs for a fixed A increases, grosso modo, as the electronegativity differences between X and A increase, with some exceptions, which reflect the differences in the relaxation energies of the radicals produced upon the bond cleavage. A similar trend, albeit less pronounced, is found for single A−X bonds, where A = C, N, O, F, P, S, and Cl. However, there is an additional feature embodied in the enhancement of the strength of the A−boron bonds due to the ability of boron to act as a strong electron acceptor. The trends in bond lengths and charge densities at the bond critical points are in line with the aforementioned behavior.

Arkivoc, ix, 305-320 (2005).

Influence of protonation on the properties derived from electron density

The effect of protonation on the electron density of a series of small molecules has been studied by means of the quantum theory of the Atoms in Molecules (QTAIM) methodology. The nonuniform redistribution of the electron density upon protonation of the systems produces an increase of the atomic energy of the protonated heteroatom and a reduction of the atomic charge for the protonated oxygen, while an increase of the charge on the protonated nitrogens is observed. The total volume of the protonated systems is smaller than that of the corresponding neutral ones. Thus, all the groups that form the molecule suffer a reduction of the volume when the systems become protonated. The transferability of the methyl group properties between the molecules studied has been analyzed. 

The Chemistry of Cyclobutanes, pg. 177-211

Acidity and basicity of cyclobutanes

Book Chapter: The Chemistry of Cyclobutanes, pg. 177-211, Ed. Z. Rappoport and J.F. Liebaman, Patai Series: The Chemistry of Functional Groups

Struct. Chem. 16, 77-79 (2005)

Doi: 10.1007/s11224-005-1089-9

Polyynes vs. Cumulenes: Their Possible Use as Molecular Wires

Polyynes and cumulenes from 2–12 atoms have been calculated at the B3LYP/6-311++G** level and their energies compared using an isodesmic reaction. The chain length has been modeled empirically affording an equation that predicts substantial variation for long chains.


Tet. Lett. 45, 4127-4129 (2004)

Doi: 10.1016/j.tetlet.2004.03.141

Classical versus redox tautomerism: substituent effects on the keto/enol and sulfoxide/sulfenic acid equilibria

MP2/6-311+G** ab initio calculations have been carried out for a classical example of tautomerism, the keto/enol [RCOCH3/RC(OH)CH2] and an example of redox tautomerism, the sulfoxide/sulfenic acid [RS(O)H/RSOH]. Eleven R substituents have been examined. Both equilibria show proportional energies and similar dependence on the Swain–Lupton Fand Rparameters.

Struct. Chem. 15, 599-604 (2004)

Doi: 10.1007/s11224-004-0735-y

The Position of the Lone Pair in Amines: A Comparison Between Bader's AIM Approach and Pure Geometrical Considerations

The position of the lone pair of 17 amines has been located with the help of Bader’s AIM methodology. This position has been compared with those estimated with simple geometrical models. It appears that these models are convenient only for some symmetrical or undistorted cases.

Collect. Czech. Chem. Commun. 69, 2134-2146 (2004)

Doi: 10.1135/cccc20042134

Protic acidity of some aliphatic and alicyclic hydrocarbons in the gas phase and in solution. An empirical and computational link

Here we report the results of the study of a set of thirteen hydrocarbons R-H not leading to extensively charge-delocalized anions R- upon ionization, R-H → R- + H+. It essentially involves the following: (i) The computation at the G2 level of the changes in thermodynamic state functions for this process in the gas phase. The reliability of the computational method was further assessed by comparison with CCSD(T)/Aug-cc-pVTZ results. (ii) A direct comparison of the experimentally available thermodynamic (gas phase) and kinetic (solution) data pertaining to this reaction. (iii) A careful re-examination of the experimental data sets and the Brønsted-type relationships derived therefrom by using the computed thermodynamic data. This treatment suggests the existence of mechanistic features affecting the experimental data and indicates the need for further experimental and computational work.

Chem. Phys. Lett. 398, 560-563 (2004)

Doi: 10.1016/j.cplett.2004.09.127

The enormous apparent gas-phase acidity of cubylamine

The high acidity of cubylamine (1NH2) seems to originate in the release of strain energy attending the breaking of some C–C bonds in 1NH. This process is greatly facilitated by the strong stereoelectronic interactions in 1NH. The anionic species thus formed are less strained, and their corresponding conjugate acids seem unable to ‘borrow strength’ from the residual strain, at least within the time-scale of the FT ICR experiments.

Angew. Chem. Int. Ed. 42, 2281-2284 (2003)

Doi: 10.1002/anie.200350993

Stereoelectronic, Strain, and Medium Effects on the Protonation of Cubylamine, a Janus-like Base

The cubic structure of cubylamine (1NH2) is maintained on protonation in aqueous solution, but in the gas phase 1NH2 is irreversibly protonated on the carbon framework, leading to the formation of iminium ions through ring opening (see scheme).