Density functional theory (B3LYP and BHandHLYP) and unrestricted second‐order Møller–Plesset (MP2) calculations have been performed using 3‐21G, 6‐31G(d,p), and 6‐311 G(2d,2p) basis sets, to study the OH hydrogen abstraction reaction from alanine and glycine. The structures of the different stationary points are discussed. Ring‐like structures are found for all the transition states. Reaction profiles are modeled including the formation of prereactive complexes, and very low or negative net energy barriers are obtained depending on the method and on the reacting site. ZPE and thermal corrections to the energy for all the species, and BSSE corrections for B3LYP activation energies are included. A complex mechanism involving the formation of a prereactive complex is proposed, and the rate coefficients for the overall reactions are calculated using classical transition state theory. The predicted values of the rate coefficients are 3.54×108 L⋅mol−1⋅s−1 for glycine and 1.38×109 L⋅mol−1⋅s−1 for alanine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1138–1153, 2001

Theoretical models are used to study pH-dependent equilibria of 2,4-diamino-5-phenylthiazole tautomer molecules in water. A complete screening of semiempirical SCF multiple minimums of hypersurfaces, corresponding to several solute-water supermolecules, has been made. Multiple minimum hypersurface searching confirms experimental NMR results indicating that the native diamine tautomer predominates in aqueous neutral and basic media. This tautomeric structure, protonated either in N3 and N4, also predominates in aqueous acid media with a minor presence of a protonated monoimine tautomer, in agreement with 1 H NMR results in D 2 O. High-level ab initio SCF MO of the main structures, where solvent reaction field effects are taken into account with a dielectric constant equivalent to that of water, predict a nonconjugated protonated monoimine tautomer in nonprotic solvents, according to 1 H NMR data in polar aprotic solvents. Calculated electron excitation patterns of hydrated species in water agreed with the experimental UV spectra at different pH values. The quantum chemical procedures for calculating total energies and frontier orbital eigenvalues in local minimum geometries of the relevant supermolecules provide an appropriate model for comparisons of theoretical results with experimental facts in the case of analytical voltametry. The frontier orbital eigenvalues of the most populated minimums discard the appearance of electroanalytic signals in the case of acidic samples because of the similarity of the predicted values for all protonated isomers and water. Experimental measurements confirm the oxidative character of electroanalytic signals.

Retinitis pigmentosa (RP) is a pathological condition associated with blindness due to progressive retinal degeneration. RP-linked mutations lead to changes at the retinal binding pocket and in the absorption spectra. Here, we evaluate the geometries, electronic effects, and vertical excitation energies in the dark state of mutated human rhodopsins carrying the abnormal substitutions M207R or S186W at the retinal binding pocket. Two models are used, the solvated protein and the protein in a solvated POPC lipid bilayer. We apply homology modeling, classical molecular dynamics simulations, density functional theory (DFT), and quantum mechanical/molecular mechanical (QM/MM) methods. Our results for the wild type bovine and human rhodopsins, used as a reference, are in good agreement with experiment. For the mutants, we find less twisted QM/MM ground-state chromophore geometries around the C(11)-C(12) double bond and substantial blue shifts in the lowest vertical DFT excitation energies. An analysis of the QM energies shows that the chromophore-counterion region is less stable in the mutants compared to the wild type, consistent with recent protein folding studies. The influence of the mutations near the chromophore is discussed in detail to gain more insight into the properties of these mutants. The spectral tuning is mainly associated with counterion effects and structural features of the retinal chain in the case of the hM207R mutant, and with the presence of a neutral chromophore with deprotonated Lys296 in the case of the hS186W mutant.