Shun-ichi Kawahara

Dinucleotide Hydrolysis Promoted by Dinuclear Zn Complexes − The Effect of the Distance between Zn Ions in the Complexes on the Hydrolysis Rate

The rate of hydrolysis of an RNA dimer, uridylyl(3′5′)uridine (UpU), promoted by dinuclear Zn complexes resulting from a series of ligands with differently spaced Zn ion binding sites, was examined. Although the ligands in the present study have in common two di-2-pyridylmethylamino moieties as the Zn binding sites, the activities of these ligands toward the hydrolysis were quite different. Our results suggest that the distance between metal ion coordination sites is an essential factor for the intrinsic activities of the dinuclear complexes.

Ab initio calculation of interaction nature of borazine (B3N3H6) dimer

The π/π interaction (stacking) and N(B)–H/π interaction of the borazine (B3N3H6) dimer were theoretically studied. In contrast to the benzene dimer, the gauche parallel-stacked dimer of borazine was energetically minimum, and total interaction energy was about 1 kcal/mol more negative than that of the parallel-stacked dimer of benzene. The gauche parallel-stacked dimer of borazine was more stable than slipped parallel-stacked dimers and T-shape dimers. The syn parallel-stacked dimer of borazine was energetically unstable and it was less stable than the slipped syn parallel-stacked structures. The electron correlation effect at higher than the second-order Moller–Plesset (MP2) level on the molecular interaction energy was quite small. The dispersion term and the charge transfer term had large contribution in almost all the borazine dimer formations, except the syn parallel-stacked dimer. In the case of syn parallel-stacked dimer, contribution of the dispersion term was dominant. The electrostatic term had ...

Electron correlation and basis set effects on strong hydrogen bond behavior: a case study of the hydrogen difluoride anion

Abstract A strong hydrogen bond between hydrogen fluoride and fluoride anions forms an anionic chemical species, i.e. a hydrogen difluoride anion. This paper describes the result of ab initio investigations on hydrogen bond behavior of the hydrogen difluoride anion, whose geometry and energy were evaluated at various computational levels of theory, from Hartree–Fock to QCISD(T) calculations using basis sets from cc-pVDZ to aug-cc-pV5Z. The MP4(SDQ) or QCISD level of calculations using aug-cc-pVTZ or a larger basis set suggested an almost constant value (2.27 A) for the atom distance between two fluorine atoms. The larger basis set was utilized, the more negative (the larger) hydrogen bond energy was suggested. But when aug-cc-pVTZ or a larger basis set was utilized, the fluctuation of the calculated values for hydrogen bond energy was less than 1 kcal/mol. Accurate estimation of the hydrogen bond energy requires MP4(SDQ) geometry optimization and subsequent QCISD(T) energy estimation. But the difference in the geometry and energy between the MP2 and QCISD results was small and, thus, the MP2 results are considered reliable despite the low computational costs. The change in the potential energy was also examined for dissociation of the hydrogen difluoride anion into hydrogen fluoride and fluoride anions. The potential energy curve obtained from the computational level of QCISD(T)/aug-cc-pVTZ//MP4(SDQ)/aug-cc-pVTZ was in good agreement with that obtained from the calculation of QCISD(T)/aug-cc-pV5Z//MP4(SDQ)/aug-cc-pVTZ.

Specific 3′-Terminal Modification of DNA with a Novel Nucleoside Analogue that Allows a Covalent Linkage of a Nuclear Localization Signal and Enhancement of DNA Stability

We report a straightforward method for the site‐specific modification of long double‐stranded DNA by using a maleimide adduct of deoxycytidine. This novel nucleoside analogue was efficiently incorporated at the 3′‐termini of DNA by terminal deoxynucleotidyl transferase (TdT). Thiol‐containing compounds can be covalently linked to the maleimide moieties. We added a nuclear localization signal peptide to the 3′‐terminal of a 350 bp‐long DNA that encoded short‐hairpin RNA, and these modifications resulted in the enhancement of silencing activity by RNA interference. This enhancement is mainly attributed to increased stability of the template DNA.

Theoretical investigation on the substitution effect of the hydrogen bond energy of the Watson-Crick type base pair between substituted 1-methyluracil and 9-methyladenine

Abstract Basis set effect in evaluation of base pair formation energy of the Watson–Crick type base pair between substituted 1-methyluracil and 9-methyladenine was studied in the Hartree–Fock and second-order Moller–Plesset level of theory. The same trend was observed in the substitution effect in all basis sets attempted; thus, the error depending on the basis set incompleteness is minimal in the evaluation of the substitution effect of the base pair formation energy. Neither the hydrogen bond distance nor the atomic charge was a valid index for the hydrogen bond status in base pairing.

Hydrogen bond cooperativity derived from neighboring hydrogen bond formation: case study in three iso-complexes of C8H9N5O2

Abstract Hydrogen bond cooperativity in heterocyclic hydrogen bond complexes was studied. The arrangement of the hydrogen bond donor (D)–acceptor (A) orientation has an important role in the cooperativity. When a hydrogen bond has been formed at the neighboring hydrogen bond site, the intrinsic hydrogen bond forming abilities of hydrogen bonding sites in the DA type molecules are increased, while those in the AA and DD type molecules are decreased.

2-Pyridone and 3-oxo-1,2,6-thiadiazine-1,1-dioxide derivatives: a new class of hydrogen bond equivalents of uracil

Hydrogen bond complex stability between adenine (A) and hydrogen bond equivalents of uracil: 2-pyridone derivatives (UXX2O) and 3-oxo-1,2,6-thiadiazine-1,1-dioxide derivatives (UXSO2) was studied, and as the result, the hydrogen bond energy of UXX2O-A and a complex of UXXSO2-A, was about 1.5xa0kcal/mol more stable than that of the corresponding adenine-uracil derivatives complex, respectively. The energy difference between the imide tautomer and enol tautomer was smaller than those of uracil derivatives. UFSO2 can form a stable complex with A, and its imide tautomer is stable.

Improvement of Targeted Gene Delivery to Human Cancer Cells by a Novel Trifunctional Crosslinker

A facile method for the construction of an immunoconjugate which displays targeting ligands, such as antibody fragments, with a high density is reported. For this purpose, we synthesized a novel trifunctional crosslinking reagent. By the use of this reagent, ligands targeting the specific cell can be displayed on the surface of the drug carrier with a high density. In this study, we display HER2 (human epidermal growth-factor receptor-2) binding ligands on branched polyethylenimine (PEI), which can form polyplexes with plasmid DNA. Kinetic analysis of the binding to the extracellular domain of HER2 show the PEI displaying a high density of ligands binds to the target more strongly compared to the PEI displaying ligands at a low density. The increased density of HER2 ligands displayed on the gene carrier contributes to the improved transfection efficiency. This approach can be applied to other drug delivery systems, including liposome, micelle, and so on.