John J. Wendoloski

Electronic structure of vinoxy radical CH2CHO

Ab initio multiconfiguration Hartree–Fock (MCHF) wave functions have been used to describe the electronic structure of vinoxy radical CH2CHO. The energy difference between the ground 2A\ state and the first excited 2A\ state is found to be 3.22 eV using a double zeta quality basis set, in good agreement with the observed transition at 3.57 eV. In addition, the calculations predict a near infrared electronic transition.

Systematic GVB study of harmonic vibrational frequencies and dipole moment derivatives: The vinyl radical C2H3 and other simple molecules

Structure, harmonic vibrational frequencies, and dipole moment derivatives of methane, ethylene, and acetylene have been obtained from generalized valence bond (GVB) wave function calculations. The results are compared to Hartree–Fock (HF) data, and other correlated wave function data. It is found that the GVB method consistently overemphasizes left–right electron correlation effects, and predicts bond lengths ∼0.01–0.02 A longer than experiment. However, the calculated harmonic frequencies are within 4.2% of the observed fundamentals and within 3.5% of the experimental harmonic frequencies. Dipole moment derivatives are in semi‐quantitative agreement with experiment. The method is used to predict the IR spectrum of the vinyl radical, including a very intense out of plane bending mode with frequency near 1000 cm−1.

Prediction of Solvation Free Energies of Small Organic Molecules: Additive-Constitutive Models Based on Molecular Fingerprints and Atomic Constants

Solvation free energy is an important molecular characteristic useful in drug discovery because it represents the desolvation cost of a ligand binding to a receptor. Most of the recent developments in the estimation of solvation free energy require the use of molecular mechanics and dynamics calculations. Group contribution methods have been rarely used in the past for calculating solvation free energy because automated prediction methods have not been developed in this regard. As an aid to combinatorial library design, we explored rapid and accurate means of computing solvation free energies from the covalent structures of organic molecules and compared the results on a test set with the GB/SA solvation model. Two independent additive-constitutive QSPR methods have been developed for the computation of solvation free energy. The first is a QSPR model (HLOGS) derived using a technique that uses the counts of distinct/similar fragments and substructures for each molecule as variables in a PLS regression. T...

Theoretical study of electrophilic addition: O(3P)+C2H4

Ab initio Hartee–Fock (HF) and multiconfiguration Hartee–Fock (MCHF) calculations have been carried out to characterize the reactants, transition state, and products of the electrophilic addition of O(3P) to the π bond of ethylene. The results show that the diradical product CH2CH2O is stable with respect to the reactants. The transition state has Cs symmetry, not C2v, with the oxygen atom localized on one of the two double‐bond C atoms.

The fundamentals of pharmacophore modeling in combinatorial chemistry

The concept of pharmacophore modeling is one of the oldest yet most widely used concepts in today’s drug discovery research. The essential substructural moieties of a molecule necessary for its pharmacological activity are called pharmacophores. This terminology was first introduced by Ehrlich (1), following the term chromophore, which was used to represent the functional groups responsible for the color of a compound. The interest in the idea of pharmacophores has grown enormously in recent years owing to the availability of various automated computerized software for identifying pharmacophores as well as their geometry (2–7). The pharmacophoric information as well as their three-dimensional structure can often be used to identify novel pharmacologically active lead compounds by searching various databases of known chemicals, like the Available Chemical Directory (ACD) (8). Compounds having similar pharmacophoric groups often have similar biological activity. Understandably, the existence of similar or the same pharmacophoric groups does not guarantee that biological activity will be similar. The differentiating structural moieties may cause enough repulsive interaction with the target protein=receptor to diminish or abolish its J. OF RECEPTOR & SIGNAL TRANSDUCTION RESEARCH, 21(4), 357–375 (2001)