Rois Benassi

Exocyclic push–pull conjugated compounds. Part 2. The effect of donor and acceptor substituents on the rotational barrier of push–pull ethylenes

Abstract The energy of the rotational barriers and electronic structure of the transition state in substituted ethylenes are discussed in the light of the results obtained from different theoretical MO ab initio approaches. The 6-31G ∗ basis set at Hartree–Fock (HF) level and with second-order Moller–Plesset perturbation theory (MP2) was employed, critical points were localized through full geometry relaxation and characterized by vibrational analysis. A multiconfigurational approach (MCSCF) with different active spaces was also employed. For alkenes the correct rotational transition state is obtained only from the MCSCF approach, whereas for push–pull olefins the HF approach with correlation corrections at MP2 level provides correct answers for the internal rotation around C(sp 2 )–C(sp 2 ) bonds. The choice is more critical when only acceptor or donor groups are present, especially when change of hybridization occurs at the atoms at the edges of the C–C bond in the critical points.

Solvent effect on keto–enol tautomerism in a new β-diketone: a comparison between experimental data and different theoretical approaches

The novel β-diketo compound (3-acetyl-4-oxopentanoic acid) OPAA is here synthesized and completely characterized in the solid state by means of X-ray crystallography and in solution by potentiometry and 1H and 13C NMR spectroscopy. In the solid state, OPAA exhibits the di-keto (DK) structure, however, in solution, we can observe a strong solvent dependent tautomeric equilibrium. Theoretical ab initio calculations employing DFT at the B3LYP/6-311G** level, and different methods of theoretical model chemistry (CBS-4M, G3MP2, CBS-QB3) are used to extensively investigate the tautomeric equilibrium and compare it with experimental data. Solvent effects are evaluated using a CPCM continuum solvation method; among all applied methods, CBS-4M is the one that better predicts experimental data and is able to qualitatively describe tautomeric equilibrium in solution, allowing thermodynamic calculations of pKa. Furthermore a supermolecular solvent approach is used to better analyze solvent–solute interactions in order to predict chemical properties.

Exocyclic push–pull conjugated compounds. Part 1. Theoretical study of the effect of ring size on the structure, electronic properties and rotational barriers of cyclic analogoues of 1,1-diamino-2,2-dicyanoethylene

Abstract An MO theoretical ab initio study was performed on 2-exo-methylene push–pull derivatives having as donor groups nitrogen atoms, components of a heterocyclic ring, and as acceptors CN and COOEt groups. Five-, six- and seven-membered ring derivatives were considered. Calculations were also performed on a number of push–pull ethylenes whose experimental properties were reported in the chemical literature in order to test the soundness of the conclusions from theoretical approaches. The physical properties calculated for the latter molecules were compared with known experimental values, in order to check the predictive ability of the theoretical approaches employed. Geometrical features and torsional barriers in solution are satisfactorily reproduced. Results were obtained with different basis sets, second-order Moller–Plesset theory, in order to perform comparisons at different theoretical levels with a view to carrying out calculations in larger molecular systems. The widest range of comparisons between calculated values for the different molecules were carried out at the HF/6-31G∗//HF/6-31G∗ level. The origin of the torsional barrier for isomer interconversion as a function of the electronic properties of these molecules is discussed, in particular by examining the polarized character of the exo double bond. The role of the lone pairs of the nitrogen atoms in the push–pull mechanism is investigated, also in competition with an unsaturated bond within the ring. The different conjugation patterns that can be exploited within these molecules is examined within the donor–acceptor model and Natural Bond Orbital (NBO) theory. Empirical correlations are proposed in order to estimate dipole moments and absorption wavelengths for the family of push–pull olefins.

Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications.

Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimers disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga(3+), Cu(2+)) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga(3+) and Cu(2+) are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2](+) was found more stable than curcumin one. Good agreement is detected between calculated and experimental (1)H and (13)C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga(3+) complexes display possible superoxide dismutase (SOD)-like activity.

Metal binding ability of curcumin derivatives: a theoretical vs. experimental approach

Theoretical calculations employing DFT at the B3LYP/6-311G++** level are used to investigate the tautomeric equilibrium in curcumin derivatives. The solvent effect is evaluated using the CPCM continuum solvation method. The results are compared with experimental data obtained from the X-ray crystal structure of K2A23 and UV-vis data. The KE tautomer is more stable in a vacuum and in the solid state, while in water the DK tautomer reaches a population of 90%. In agreement with spectroscopic data, theoretical calculations predict a slight prevalence of the DK form in non-aqueous solvent systems. The ability to chelate metal ions [Fe(3+), Ga(3+) and Cu(2+)] is then explored by means of (1)H, (13)C NMR and UV-Vis spectroscopy. From the calculation of the overall stability constants of metal complexes and (1)H NMR titrations with Ga(3+), it is clear that the more stable species has a 1 : 2 M/L molar ratio. The curcuminoid coordinates the metal ion through the keto-enol function in the dissociated form; in addition 2D (1)H (13)C NMR experiments suggest the involvement of carboxylic oxygen in metal coordination it was found in the solid state for the complex [Ga(K2A33)2]PF6. The rate of the complexation reaction is strongly influenced by the type of substituent on the aromatic ring of the curcuminoid (K2A33 ≈ K2A23 ≫ K2A21). In addition DPPH assay evidences how antioxidant ability of curcumin derivatives is mainly due to the presence of a phenolic group and metal coordination by a keto-enolic moiety does not affect it, especially for K2A21.

Exocyclic push–pull conjugated compounds. Part 3. An experimental NMR and theoretical MO ab initio study of the structure, the electronic properties and barriers to rotation about the exocyclic partial double bond in 2-exo-methylene- and 2-cyanoimino-quinazolines and -benzodiazepines

Abstract The structure of a number of 2-exo-methylene substituted quinazolines and benzodiazepines, respectively, 1, 3a,b, 4 ( X=–CN, –COOEt ) and their 2-cyanoimino substituted analogues 2, 3c,d ( X=–CN, –SO 2 C 6 H 4 –Me (p) was completely assigned by the whole arsenal of 1D and 2D NMR spectroscopic methods. The E/Z isomerism at the exo-cyclic double bond was determined by both NMR spectroscopy and confirmed by ab initio quantum chemical calculations; the Z isomer is the preferred one, its amount proved dependent on steric hindrance. Due to the push–pull effect in this part of the molecules the restricted rotation about the partial C2,C11 and C2,N11 double bonds, could also be studied and the barrier to rotation measured by dynamic NMR spectroscopy. The free energies of activation of this dynamic process proved very similar along the compounds studied but being dependent on the polarity of the solvent. Quantum chemical calculations at the ab initio level were employed to prove the stereochemistry at the exo-cyclic partial double bonds of 1–4, to calculate the barriers to rotation but also to discuss in detail both the ground and the transition state of the latter dynamic process in order to better understand electronic, inter- and intramolecular effects on the barrier to rotation which could be determined experimentally. In the cyanoimino substituted compounds 2, 3c,d, the MO ab initio calculations evidence the isomer interconversion to be better described by the internal rotation process than by the lateral shift mechanism.

Computational electrochemistry. Ab initio calculation of solvent effect in the multiple electroreduction of polypyridinic compounds

Abstract The electrochemical multiple reduction of a series of polypyridinic compounds, yielding mono, di and trianionic species is theoretically studied. Calculated electron affinity values were used to obtain molecular-structure/reactivity relationships, the latter reflected by the experimental half-wave electroreduction potentials. Gas-phase electron affinity data vs. half-wave potentials produced satisfactory linear correlations, but separated for each successive electron transfer step (i.e. a linear relationship for the first electron transfer, yield of the monoanion, neatly separated from the one concerning the second electron transfer, yield of the dianionic species). The theoretical approach was pushed further, also including solvent effects. This was done by means of two methods based on the continuum solvation model: the Onsager cavity (SCRF) and the more sophisticated SM5.42R solvation models. In particular, the latter is able to group in a single correlation the potentials referring to the first, second and third electron transfer.

Conformational properties and homolytic bond cleavage of organic peroxides. I: an empirical approach based upon molecular mechanics and ab initio calculations

The conformational features of a large number of hydroperoxides ROOH and peroxides ROOR′, where R and R′ are alkyl groups of different and increasing size and phenyl rings, including ortho substituted derivatives, were obtained from molecular mechanics calculations by employing a standard package. For the molecules of small molecular size, comparison was carried out with the results of ab initio calculations. Heats of formation were also obtained from molecular mechanics for hydroperoxides and peroxides: The values are, in general, overestimated. For the molecules containing the CF3 group, the calculated values are subject to large errors and heats of formation were obtained from ab initio total energies in the “atom equivalents” scheme. To estimate the homolytic dissociation energies of the different bonds in the peroxide molecules, heats of formation of R·, ·OR, and ·OOR radicals were employed and several of them had to be calculated. Different approaches were employed—molecular mechanics calculations, ab initio energies within the atom equivalent and isodesmic reaction schemes, and Bensons group additivity rule; values consistent within the different calculation methods were chosen for estimating dissociation energies. The bond dissociation energies indicate different trends in these molecules as a function of the nature of the R and R′ groups and the possible electronic effects operating in these molecules are discussed.

Homolytic bond-dissociation in peroxides, peroxyacids, peroxyesters and related radicals: ab-initio MO calculations.

Abstract Homolytic dissociation energies for different cleavage paths in a number of peroxides peroxyacids and peroxyesters and in the radicals formed from these molecules, were calculated from the total MO ab-initio molecular energies of the chemical species involved in the bond cleavage reactions and compared with experimental values, where known.

Conformational preference in methylphenyl sulphoxide and in ortho substituted fluorine derivatives: a theoretical approach

Ab initio MO calculations (3-21G*//3-1G* basis set) have been performed for methylphenyl sulphoxide (1), 2-fluoro- (2) and 2,6-difluoro- (3) derivatives in order to examine the structural properties of their conformational ground state (s). The conformational energy profile for rotation around the Car. -S bond has been constructed in the STO-3G* basis set and the minima have been located at the 3-21G* level allowing relaxation of the geometrical parameters of the methylsulphinyl group. For methylphenyl sulphoxide one energy minimum is found and corresponds to the SO bond nearly eclipsed with the phenyl ring (twist angle 7.31°). Two energy minima are found for compound 2 and in the more stable conformation the SO bond is coplanar with the ring and anti with respect to the ortho fluorine substituent. In the less stable ground state the lone pair of the sulphur atom settles in the nodal plane of the π-electron cloud of the phenyl ring. This conformation is structurally close to the conformational ground state of compound 3. For compound 1 the properties of the transition state have also been determined at the 3-21G* level. The energy barrier for internal rotation corresponds to the S-C bond of the methyl sulphinyl group eclipsed with one ortho C-H bond. The origin of the conformational ground- and transition-states in these molecules is discussed on the basis of their electronic structure.