Patrick Redington

MOLFIT: A computer program for molecular superposition

Abstract MOLFIT is a program that performs the task of molecular superposition, using a combination of two algorithms. The first is a direct solution and is developed here. The second is a refinement of the algorithm of (Sippl & Stegbuchner (1991) Computers Chem. 15 , 73 (SS). This combination provides a robust and efficient algorithm, obtaining accurate solutions for cases where the individual methods failed.

A conformational basis for the selective action of ara-adenine.

Abstract The glycosidic “high anti” conformation is postulated to be the conformation required by the enzymes adenosine kinase and inosine phosphorylase. Purine analogs that are stable in this conformation are either effective substrates or inhibitors of these enzymes. Ara-adenine is shown to be highly unstable in the high anti conformation. The inactivity of ara-adenine as a substrate for both adenosine kinase and inosine phosphorylase is attributed to its inability to assume the high anti conformation specified by these enzymes. That adenosine itself has a local minima in the high anti conformation, as does inosine and guanosine, is required by its ability to inhibit the synthesis of uridylic acid. The minimal cytotoxic properties of ara-adenine is a consequence of its failure, in normal cells, to be converted to the toxic nucleotide form. The ability of ara-adenine to selectively inhibit DNA viruses means that in DNA virus infected cells the conversion of ara-adenine to ara-AMP is facilitated through a mechanism that does not require a substrate high anti conformation. It is apparent that selective antiviral and anticancer nucleoside analogs may be constructed if their conversion to the toxic nucleotide form is prohibited in normal tissues but allowed in cancer cells or virus infected cells. The basis for the selective effects of ara-adenine is that normal cells require a substrate conformation in which ara-adenine is unstable but that certain neoplastic and viral mechanisms for the conversion of ara-adenine to ara-AMP exist which are able to utilize ara-adenine in its stable syn or anti conformations.

An explicit series for the semiempirical analysis of NMR coupling constants

Abstract An iterative series for calculating NMR coupling constants is developed. The development is based on the unrestricted Hartree-Fock treatment of coupling constants and serves as an alternative to finite perturbation theory. The series is broken down into several terms which can be summed separately using the multinomial expansion. The first and third terms have explicit dependence on local properties while the second depends on the symmetry and dispersion of the molecular orbitals. These formulas may be used to relate the changes in the coupling constant in a homologous series of molecules to properties such as bond order, ionization energies, etc. They may also be used in direct conjunction with a semiempirical program to calculate a molecules coupling constants.

Local density functional calculations on metathesis reaction precursors

Calculations were carried out to assess the role of Local Density Functional (LDF) programs in following the course of metathesis reactions in large molecular systems. This study was designed to provide preliminary information on: (1) the nature of weakly bound ligands in cocatalyst structures, (2) the influence of phenyl ring substitution on catalytic activity, (3) the role of AlCl3 as a cocatalyst, and (4) the influence of macroenvironment on the basic electronic structure of the reactive site. For this purpose, calculations were carried out on an MoCl4O/tetrahydrofuran (THF) complex, ring substituted derivatives of MoCl5O-phenyl, the basic metallacyclobutane ring prototype, Mo(CH2)3CH3ClO/AlCl3, and a large fluorinated molybdenum complex.

G Matrix assembly and SCF iteration damping

Abstract Some simplifications to Dukes method for assembly of the G matrix are presented. These modifications make it more efficient and applicable on machines with word lengths shorter than 60 bits. Additionally an improvement to the SCF iterative damping scheme of de Montogolfier and Horeau is given.

An explicit model for the NMR coupling constant of the hydrogen molecule and the breakdown of INDO-FPT

Abstract We have previously obtained explicit equations, which are based on the ideas of finite perturbation theory (FPT), for calculating NMR proton-proton coupling constant. Using this model and the INDO formalism, a simple closed-form expression for the coupling constant of the hydrogen molecule is developed. This expression has several unique features: it shows that the convergence criteria for the iterative calculation is ¦ x ¦ x = HH /ΔϵX and it allows the H 2 coupling constant to be expressed directly in terms of the semiempirical parameters, showing specifically how each parameter affects the coupling constant. In this way the formalism of semiempirical SCF Theory lends itself to the construction of a model for coupling constants which is not purely numerical in nature. An INDO-FPT calculation is developed for the hydrogen molecule. As long as parameters are chosen for which ¦ x ¦ x ¦ > 1, the UHF calculation breaks down, the extremum corresponding to symmetrical molecular orbitals no longer being the minimum.