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Tetrapyrrolinone somatostatin (SRIF) mimetics (cf. 1), based on a heterochiral (d,l-mixed) pyrrolinone scaffold, were designed, synthesized, and evaluated for biological activity. The iterative synthetic sequence, incorporating the requisite functionalized coded and noncoded amino acid side chains, comprised a longest linear synthetic sequence of 23 steps. Binding affinities at two somatostatin receptor subtypes (hsst 4 and 5) reveal micromolar activity, demonstrating that the d,l-mixed pyrrolinone scaffold can be employed to generate functional mimetics of peptide β-turns.

The reaction space map (RESMAP) representation is proposed for the comprehensive description of the chlorination and dechlorination reactions of polychlorobenzenes. By using the B3LYP/6-311G** energies and by assuming the chemical reactions which govern the chlorination and dechlorination processes of polychlorobenzenes, the relative energies of polychlorobenzenes and polychlorophenyl radicals were defined artificially. They were collected as the RESMAP which has the relative energies of polychlorobenzenes at the diagonal parts and the polychlorophenyl radicals connecting two polychlorobenzenes at the off-diagonal parts. The RESMAPs created for three models for the chlorination/dechlorination processes provided a general view of the thermodynamically controlled isomer distributions and chlorination/dechlorination reaction patterns for benzene and (poly)chlorinated benzenes.

A combination of Monte Carlo (MC) simulation and ab initio molecular orbital (MO) calculation was applied to dimethyl nitroxide (DMNO) in H2O, CH3OH, CH3CN, and (CH3)2CO solutions, and the solvent effect on the electronic structure and n−π* and π−π* excitation energies was analyzed. The solution structures were generated by MC simulations, and the ROHF-SCI calculation with the MIDI-4 basis set was carried out for each solution structure. The electronic structure and excitation energies in the four solutions were obtained by averaging the 100 solution structures for each solution. Solvent effect was calculated by the point charge model and supermolecule model. In the point charge model, all solvent molecules were approximated by point charges at atomic nuclei, while in the supermolecule model the solute molecule and some of the solvent molecules were treated as a supermolecule surrounded by other solvent molecules approximated by point charges. The calculated n−π* excitation energy increased (blue shift) in the four solvents as compared to that in the gas phase. The magnitude of the solvent effect reflects the dielectric constant of the solvent. The calculated En-π* value in CH3OH was larger than that in CH3CN, whose dielectric constant is larger than that of CH3OH. This is due to the hydrogen-bonding ability of CH3OH and agrees well with experiment. The π−π* excitation energy was predicted to decrease in the four solvents, although the red shift was overestimated. The solvent effect was well elucidated by using the Mulliken charges of DMNO in the ground state and the excited states and the electrostatic potential generated by the solvent molecules.

A new nonempirical method of determining the effective pair potential functions which are suitable for the molecular simulation of heterolysis reactions has been proposed. The self-energy correction due to the polarization in solution was estimated by the ab initio GB calculation which includes the solvent effect by the continuum model using the generalized Born formula, and the polarization caused by solvation was incorporated in the effective pair potential functions. The method was applied to the ionic fragmentation reaction of t-BuCl in aqueous solution. The effective pair potential functions between t-BuCl and water were determined at 12 different C−Cl distances, and expressed by analytical functions which cover the whole reaction stage, from the covalent bonding region to the dissociated free ions. The Monte Carlo simulation and statistical perturbation theory using the effective pair potential functions determined the free energy profile of the reaction with a reasonable dissociation energy.

A combination of Monte Carlo (MC) simulation and ab initio molecular orbital (MO) calculation was applied to dimethyl nitroxide (DMNO) in H2O, CH3OH, CH3CN, and (CH3)2CO solutions, and the solvent effect on the electronic structure and hyperfine coupling constant (hfcc) of nitrogen in DMNO was analyzed. The solution structures were picked up from the MC simulations, and a ROHF-SCI calculation with the MIDI-4 basis set was carried out for a supermolecule including one DMNO and a few solvent molecules surrounded by other solvent molecules approximated by point charges. The calculated hfcc of the N atom in DMNO in these solvents reflects the dielectric constant and the hydrogen-bonding ability of solvent and agrees with the experimental trend observed for di-tert-butyl nitroxide in solutions. In the H2O and CH3OH solutions, there are solvent molecules that are hydrogen-bonding and have a strong interaction with DMNO. For this interaction, the hfcc is larger in the CH3OH solution than in the CH3CN solution, although the dielectric constant of CH3CN is larger than that of CH3OH. Electron transfer between DMNO and the solvent molecules was acting in two directions:  one from DMNO to solvent molecules around the N−O group and the other from solvent molecules to DMNO around the methyl groups. These electron transfers polarize the π-electron system of DMNO in the same direction as the electrostatic interaction does and increase the hfcc of the N atom.

The steric contact spaces associated with the reaction of the enantiomeric isomers of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[α]pyrene (I) with the exocyclic amino group of guanine of dinucleoside dimer structures were examined for a fixed transition-state geometry. This reaction is sterically prohibited for the B form DNA conformation. If, however, the nucleic acid structure is deformed, such that the distance between two adjacent base pairs (one containing guanine and cytosine) is maximized, sterically allowed transition-state geometries can be identified. It was not possible to uniquely identify the preferred transition-state complex with respect to nucleic acid structure or isomer of I. However, two types of general transition-state geometries were observed. In one, I was located “outside” the nucleic acid structure; in the other geometry, I was intercalated between adjacent base pairs in the transition state. The intercalation process might serve as a physical catalyst for the alkylation of NH2-guanine by I.

Perturbation effects of additional linkers on the spin−spin coupling in biphenyl-4,4‘-dinitrene (1) were examined by introducing a linking group between 2- and 2‘-positions of 1. Five different doubly linked systems showed triplet ESR spectra corresponding to quinonoid dinitrenes. Curie law analyses suggested that all those triplet states were thermally excited triplet states. In addition, the singlet−triplet energy gaps, which were determined by the Curie law analyses, were well correlated with their corresponding zero-field-splitting (zfs) D values. The result could be explained by the stability of dinitrene character which is estimated from the resonance energy of the intervening π-system. Our semiempirical molecular orbital calculations supported the experimental correlation between the singlet−triplet energy gap and the zfs D value.