Adsorption of Molecules on a Charged Polarizable Surface in an Electrolyte.

We present a method for the calculation of the binding and rotational energies of neutral (H2S) and charged (HS-) molecules impinging upon a charged and polarizable (Cu <100>) surface in the presence of an electrolyte. A molecular surface is constructed surrounding the H2S and HS- molecules forming boundary elements. A coupled Schrödinger-Poisson-Boltzmann iterative procedure treats the electronic structure of the molecules at the 6-31G**/MP2 level of theory and includes solvation effects through the single and double layers of charge induced by the electronic distribution. The molecule, together with its charged layers, forms a molecular single and double layer, an object which then interacts with a polarizable Gouy-Chapman plane within the electrolyte. The induced charge at the molecular surface resulting from this external electric field is obtained by solving a second set of boundary element equations. The induced polarization of the solid surface created by the impinging molecular ion is treated by a modified method of images. Repulsive interactions between the atoms of the molecule and those of the surface are obtained using a rigid-ion Hartree-Fock method. Binding energies of the molecule to the surface are determined as a function of the real surface charge imposed and also the ionic strength of the solution. It is found that surface charges can completely (180 degrees) reorient these molecules and that the counterions in the solution can completely screen binding effects of even large surface charges. Solid surface polarization can be significant in low dielectric constant solvents and is also reduced by counterions. Copyright 1998 Academic Press.

Polarization-Induced Atomic Reconfigurations of Glycine on a Metal Surface

The atomic reconfigurations of the simplest amino acid, glycine, at a realistic metal surface including a step and real surface charge are calculated. A boundary-element method for determining the polarization-induced binding of molecules to surfaces in the presence of a dielectric is coupled to quantum-chemical calculations of the gas-phase molecule. Enthalpies and potentially derived fractional charges are determined using 6-31G** basis functions and MP2 level of theory for 216 different configurations of glycine. A parameterized model captures the quantum results as a function of bond lengths, angles, and dihedrals (average deviation of <1 kcal/mol). The molecule interacts with a discretized substrate, a face-centered cubic metal slab. The slab is treated as an explicit region of lattice atoms which may include real charge, requiring the boundary conditions and hence the formalism of R. J. Zauhar and R. S. Morgan [J. Mol. Biol. 186, 815 (1985)] to be modified. The results indicate that anionic glycine is bound to a Cu <100> surface by approximately 1.6 eV in the presence of a step of atomic dimensions in a geometric configuration in agreement with the experiments of K. Uvdal, P. Bodo, A. Ihs, B. Liedberg, and W. R. Salaneck [J. Colloid Interface Sci. 140, 207 (1990)]. Neutral glycine and zwitterionic glycine are found to be oriented with their N ends toward a neutral surface in agreement with experiment. These molecules are furthermore found to undergo a critical phenomenon: Their molecular orientation "flips" by 180° with the introduction of a small, critical magnitude of real surface charge.

Synthesis of dicationic diarylpyridines as nucleic-acid binding agents.

The syntheses of 2,6-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]pyridine 7, 2-[4-(4,5-dihydro-1H-imidazol-2-yl)-phenyl]-6-[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]pyridine 8 and 2,6-bis[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]pyridine 9 in five steps from the appropriately substituted bromoacetophenone are described. 3,5-Bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]pyridine 13 is also reported, prepared in four steps from 4-bromophenylacetonitrile. The preparation of 2,5-bis[4-(4,5-dihydro-1H-imidazol-2-yl)-phenyl]pyridine 18 from 4-bromoacetophenone in six steps is presented. The dications bind to poly dA·dT in the order 7 > 13 > 18 > 8 > 9; the order of binding to poly A·U is 7 > 13 > 8 > 9; 18 essentially does not bind to the RNA model. Only 7 inhibits topoisomerase II at millimolar concentrations. The dicationic compounds that were tested against Pneumonocystis carinii in the immuno-suppressed rat model show only modest activity and are moderately toxic. Some of the compounds demonstrated modest anti-HIV-1 activity and selectivity in primary lymphocytes.

Synthesis of dicationic diaryltriazines nucleic acid binding agents.

- The synthesis of 2,4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-1,3,5-triazine 6a and 2,4-bis[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]-1,3,5-triazine 6b in 3 steps from either 4-bromobenzamidine or 4-(carbamoyl)benzamidine is reported. The synthesis of 4,6-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-2-dimethylamino-1,3,5-triazine 9a and 4,6-bis[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]-2-dimethylamino-1,3,5-triazine 9b in 2 steps from 1,4-dicyanobenzene is also described. The compounds 6b and 9b bind strongly to DNA model sequences and inhibit topoisomerase II from 2 microbial sources. Compounds 6a and 9a bind to both DNA and RNA model sequences whereas 6b and 9b essentially do not bind to the RNA model.