Small Transition-Metal Mixed Clusters as Activators of the C-O Bond. FenCum-CO (n + m = 6): A Theoretical Approach.

Binding of carbon monoxide, CO, and its activation on the surface of the FenCumCO (n + m = 6) clusters are studied in this work. Using the BPW91/6-311 + G(2d) method, we have found that adsorption of the CO molecule on the surface of FenCum (n + m = 6) clusters is thermochemically favorable. Atop and bridge CO cluster coordinations appear for pure, Fe6 and Cu6, and mixed, Fe2Cu4 and Fe4Cu2, clusters. Threefold coordination takes place for Fe3Cu3-CO where the CO bond length, dCO, suffers a largest increase from 1.128 ± 0.014 Å for bare CO up to 1.21 Å. The CO stretching, νCO, as an indicator for the CO bond weakening is redshifted, from 2099 ± 4 cm-1 for isolated CO up to 1690 cm-1 for Fe3Cu3CO and 1678 cm-1 for Fe6CO. In addition, in Cu6CO, the strongest CO bond is slightly weakened as it has a bond length of 1.15 Å and a νCO of 2029 cm-1. There is a correlation between the CO bond weakening and the increase of CO coordination in FenCumCO, which in turns promotes the transference of charges from the metal core into the antibonding orbitals of CO. Substitution of up to three Cu atoms in Fe6 increases the adsorption energies and the activation of CO. Indeed, FenCum (n + m = 6) are promising clusters to catalyze CO dissociation, particularly Fe3Cu3, Fe5Cu, and Fe6, which have large CO bond lengths and CO adsorption energies. The Bader analysis of the electronic density indicates that FenCumCO species with threefold coordination show a rise in the C-O covalent character due to the less electronic polarization. They also show important M → CO charge transfer, which favors the weakening of the CO bond.

Carbon Monoxide Activation on Small Iron Magnetic Cluster Surfaces, FenCO, n = 1-20. A Theoretical Approach.

The chemical activation of the carbon monoxide (CO) molecule on the surface of iron clusters Fen (n = 1-20) is studied in this work. By means of density functional theory (DFT) all-electron calculations, we have found that the adsorption of CO over the bare magnetic Fen (n = 1-20) clusters is thermochemically favorable. The Fen-CO interaction increases the C-O bond length, from 1.128 ± 0.014 Å, for isolated CO, up to 1.251 Å, for Fe9CO. Also, the calculated wavenumbers associated with the stretching modes νCO are decreased, or red-shifted, as another indicator of the CO bond weakening, passing from 2099 ± 4 to 1438 cm-1. Markedly, wavenumbers of vibrational modes νCO agree admirably well in comparison with experimental results reported for FenCO (n = 1, 18-20), getting small errors below 2.6%. The C-O bond is enlarged on the FenCO (n = 1-20) composed systems, as the CO molecule increases its bonding, charge transference, and coordination with the iron cluster. Therefore, small bare iron particles Fen (n = 1-20) can be proposed to promote the CO dissociation, especially Fe9CO, which has been proven to obtain the most prominent activation of the strong C-O bond by means of the charge transference from the metal core.

Chemical Equilibrium of Zinc Acetate Complexes in Ethanol Solution. A Theoretical Description through Thermodynamic Cycles.

The Gibbs free energy of complexation between the Zn(II) species and acetate ligands, forming the [Zn(OAc)n]2-n complexes with n = 1, 2 in an ethanol solution, was assessed by two different theoretical protocols based on thermodynamic cycles. In both approaches, the solution phase Gibbs free energy of each reaction is computed by summing up contributions from gas phase thermochemistry calculations to solvation Gibbs free energies obtained in a hybrid fashion, i.e., each (neutral or electrically charged) solute was first solvated by explicit solvent molecules in order to capture relevant (micro) solute-solvent and/or solvent-solvent interactions and then, a continuum model calculation is performed in order to get the corresponding bulky solute-solvent contributions. For our first thermodynamic protocol, here denominated as variant 1, a set of x independent solvent molecules are used to screen each of the involved solutes, while the variant 2 strategy uses the fact that a set of solvent molecules may exist as aggregates (or molecular clusters) in the solvent macroscopic media, before the solvation process of solutes. Our selected quantum theoretical protocol was the M05-2X/6-31+G(d)/SMD level. We made a systematic exploration about the influence of several sources of errors, such as the solvent conformation, the number of solvent molecules used to screen each of the involved solutes, the coordination geometry of the metallic center before and after the complexation process, and the pertinence of using molecular geometries optimized in gas phase and in ethanol solution, for the computation of the Gibbs free energy variation regarding the two chemical reactions under study. We set an accuracy threshold equal or less than 4.0 kcal·mol-1, with respect to the corresponding experimental records. The robustness of our thermodynamic strategies was then tested by computing the gas phase free energy contributions to the (solution phase) reaction free energies here assessed, using different density functional approximations, namely the M05-2X, BH&HLYP, PBE0, ωb97X-D and M06-2X functionals in conjunction with the larger 6-311+G(d,p) basis set.

Tautomeric ratio and prototropic equilibrium constants of tenoxicam, a 1H and 13C NMR theoretical and experimental study.

The determination of the micro-equilibrium prototropic constants is often a tough task when the tautomeric ratio favors one of the species or when the chemical exchange is not slow enough to allow the quantitative detection of the tautomeric species. There are just few experimental methods available to reveal the constants of the tautomeric micro-equilibriums; its applicability depends on the nature of the tautomeric system. A combination of experimental and quantum chemistry calculated (1)H and (13)C NMR chemical shifts is presented here to estimate the population of the species participating in the tautomeric equilibriums of the tenoxicam, an important anti-inflammatory drug. A multivariate fitting of a fraction-mol-weighted contribution model, for the NMR chemical shifts of the species in solution, was used to find the populations of the tautomers of tenoxicam. To consider and evaluate the effect of the solvent polarity on the tautomers' populations, experimental determinations were carried out in DMSO-d(6), in an equimolar DMSO-H(2)O mixture of deuterated solvents and in D(2)O. Additionally, by employing HYPNMR, it has been possible to refine the acid-base macroscopic constants of tenoxicam.

First-principles prediction of the pK(a)s of anti-inflammatory oxicams.

The gas- and aqueous-phase acidities of a series of oxicams have been computed by combining M05-2X/6-311+G(3df,2p) gas-phase free energies with solvation free energies from the CPCM-UAKS, COSMO-RS, and SMD solvent models. To facilitate accurate gas-phase calculations, a benchmarking study was further carried out to assess the performance of various density functional theory methods against the high-level composite method G3MP2(+). Oxicams are typically diprotic acids, and several tautomers are possible in each protonation state. The direct thermodynamic cycle and the proton exchange scheme have been employed to compute the microscopic pK(a)s on both solution- and gas-phase equilibrium conformers, and these were combined to yield the macroscopic pK(a) values. Using the direct cycle of pK(a) calculation, the CPCM-UAKS model delivered reasonably accurate results with MAD ~ 1, whereas the SMD and COSMO-RS models' performance was less satisfactory with MAD ~ 3. Comparison with experiment also indicates that direct cycle calculations based on solution conformers generally deliver better accuracy. The proton exchange cycle affords further improvement for all solvent models through systematic error cancellation and therefore provides better reliability for the pK(a) prediction of compounds of these types. The latter approach has been applied to predict the pK(a)s of several recently synthesized oxicam derivatives.

Theoretical analysis of hydrogen bonding in catechol-n(H(2)O) clusters (n = 0...3).

The electronic structure and hydrogen bonding of the stable isomers of catechol and its complexes with one to three water molecules is studied by means of theoretical methods. A conformational analysis based on a simulated annealing search on the potential energy surface of each complex was carried out previous to the quantum chemical energy minimization. Twenty three stable conformers were found including some involving a pi-interaction between the catechol moiety and a water molecule. The topological properties of the electron density reveal the presence of an intramolecular hydrogen bond only in the case of one complex with three water molecules. The infrared spectra of these molecules were computed and compared to available experimental results. An alternative assignment of the experimental vibrational spectrum within the range 3340-3750 cm(-1) of the catechol-3(H(2)O) complex (M. Gerhards, C. Unterberg, and K. Kleinermanns, Phys. Chem. Chem. Phys. 2000, 2, p. 5538) is proposed. The red-shift observed for the stretching vibrational frequency of the catechol hydrogen donor hydroxyl group in the presence of water molecules is rationalized in terms of the properties of the electron distribution and a Darwinian family tree is proposed to classify the diverse structural and energetic characteristics of the stable complexes found.

Determination of pKa values of tenoxicam from 1H NMR chemical shifts and of oxicams from electrophoretic mobilities (CZE) with the aid of programs SQUAD and HYPNMR.

In this work it is explained, by the first time, the application of programs SQUAD and HYPNMR to refine equilibrium constant values through the fit of electrophoretic mobilities determined by capillary zone electrophoresis experiments, due to the mathematical isomorphism of UV-vis absorptivity coefficients, NMR chemical shifts and electrophoretic mobilities as a function of pH. Then, the pK(a) values of tenoxicam in H(2)O/DMSO 1:4 (v/v) have been obtained from (1)H NMR chemical shifts, as well as of oxicams in aqueous solution from electrophoretic mobilities determined by CZE, at 25 degrees C. These values are in very good agreement with those reported by spectrophotometric and potentiometric measurements.

Ab initio model studies of copper binding to peptides containing a His-His sequence: relevance to the beta-amyloid peptide of Alzheimer's disease.

Two of the defining hallmarks of Alzheimer's disease (AD) are deposits of the beta-amyloid peptide, Abeta, and the generation of reactive oxygen species, both of which may be due to the Abeta peptide coordinating metal ions. The Cu2+ concentrations in cores of senile plaques are significantly elevated in AD patients. Experimental results indicate that Abeta1-42 in particular has a very high affinity for Cu2+, and that His13 and His14 are the two most firmly established ligands in the coordination sphere of the copper ion. Quantum chemical calculations using the unrestricted B3LYP hybrid density functional method with the 6-31G(d) basis set were performed for geometries, zero point energies and thermochemistry. The effects of solvation were accommodated using the CPCM method. The enthalpies were calculated with the 6-311+G(2df,2p) basis set. Calculations show that when Cu(H2O)(4)2+ combines with the model compound 1 (3-(1H-imidazol-5-yl)-N-[2-(1H-imidazol-5-yl)ethyl] propanamide) in the aqueous phase, the most stable binding site involves the Npi atoms of His13 and His14 as well as the carbonyl of the intervening backbone amide group. These structures are fairly rigid and the implications for conformational changes to the Abeta backbone are discussed. In solution at pH=7, Cu2+ promotes the deprotonation and involvement in the binding of the backbone amide nitrogen in a beta-sheet like structure. This geometry does not induce strain in the peptide backbone, making it the most likely representation of that portion of the Cu2+-Abeta complex monomer in aqueous solution.

Binding affinities for models of biologically available potential Cu(II) ligands relevant to Alzheimer's disease: an ab initio study.

A systematic study of the binding affinities of the model biological ligands X: = (CH3)2S, CH3S-, CH3NH2, 4-CH3-imidazole (MeImid), C6H5O-, and CH3CO2- to (NH3)i(H2O)3-iCu(II)-H2O (i = 3, 2, 1, 0) complexes has been carried out using quantum chemical calculations. Geometries have been obtained at the B3LYP/ 6-31G(d) level of theory, and binding energies, Delta, relative to H2O as a ligand, have been calculated at the B3LYP/6-311+G(2df,2p)//B3LYP/6-31G(d) level. Solvation effects have been included using the COSMO model, and the relative binding free energies in aqueous solution (Delta) have been determined at pH 7 for processes that are pH dependent. CH3S- (Delta = -16.0 to -53.5 kJ mol(-1)) and MeImid (Delta = -18.5 to -35.2 kJ mol(-1)) give the largest binding affinities for Cu(II). PhO- and (CH3)2S are poor ligands for Cu(II), Delta = 20.6 to -9.7 and 19.8 to -3.7 kJ mol(-1), respectively. The binding affinities for CH3NH2 range from -0.8 to -15.0 kJ mol(-1). CH3CO2- has Cu(II) binding affinities in the ranges Delta = -13.5 to -32.4 kJ mol(-1) if an adjacent OH bond is available for hydrogen bonding and Delta = 10.1 to -4.6 kJ mol(-1) if this interaction is not present. In the context of copper coordination by the Abeta peptide of Alzheimer's disease, the binding affinities suggest preferential binding of Cu(II) to the three histidine residues plus a lysine or the N-terminus. For a 3N1O Cu(II) ligand arrangement, it is more probable that the oxygen ligand comes from an aspartate/glutamate residue side chain than from the tyrosine at position 10. Methionine appears unlikely to be a Cu(II) ligand in Abeta.

Computational studies of Cu(II)/Met and Cu(I)/Met binding motifs relevant for the chemistry of Alzheimer's disease.

A systematic study of the binding motifs of Cu(II) and Cu(I) to a methionine model peptide, namely, N-formylmethioninamide 1, has been carried out by quantum chemical computations. Geometries of the coordination modes obtained at the B3LYP/6-31G(d) level of theory are discussed in the context of copper coordination by the peptide backbone and the S atom of a methionine residue in peptides with special emphasis on Met35 of the amyloid-beta peptide (Abeta) of Alzheimer's disease. The relative binding free energies in the gas phase, DeltaG(g), are calculated at the B3LYP/6-311+G(2df,2p)//B3LYP/6-31G(d) level of theory, and the solvation affects are included by means of the COSMO model to obtain the relative binding energies in solution, DeltaG(aq). A free energy of binding, DeltaG(aq) = -19.4 kJ mol(-1), relative to aqueous Cu(II) and the free peptide is found for the most stable Cu(II)/Met complex, 12. The most stable Cu(I)/Met complex, 23, is bound by -15.6 kJ mol(-1) relative to the separated species. The reduction potential relative to the standard hydrogen electrode is estimated to be E degrees (12/23) = 0.41 V. On the basis of these results, the participation of Met35 as a low affinity binding site of Cu(II) in Abeta, and its role in the redox chemistry underlying Alzheimer's disease is discussed.

Comparison of the kinetics and thermodynamics for methyl radical addition to C=C, C=O, and C=S double bonds.

The barriers, enthalpies, and rate constants for the addition of methyl radical to the double bonds of a selection of alkene, carbonyl, and thiocarbonyl species (CH(2)=Z, CH(3)CH=Z, and (CH(3))(2)C=Z, where Z = CH(2), O, or S) and for the reverse beta-scission reactions have been investigated using high-level ab inito calculations. The results are rationalized with the aid of the curve-crossing model. The addition reactions proceed via early transition structures in all cases. The barriers for addition of methyl radical to C=C bonds are largely determined by the reaction exothermicities. Addition to the unsubstituted carbon center of C=C double bonds is favored over addition to the substituted carbon center, both kinetically (lower barriers) and thermodynamically (greater exothermicities). The barriers for addition to C=O bonds are influenced by both the reaction exothermicity and the singlet-triplet gap of the substrate. Addition to the carbon center is favored over addition to the oxygen, also both thermodynamically and kinetically. For the thiocarbonyl systems, addition to the carbon center is thermodynamically favored over addition to sulfur. However, in this case, the reaction is contrathermodynamic, addition to the sulfur center having a lower barrier due to spin density considerations. Entropic differences among corresponding addition and beta-scission reactions are relatively minor, and the differences in reaction rates are thus dominated by differences in the respective reaction barriers.