Toshiaki Matsubara

Density functional study of the binding of the cyclen-coordinated M(II) (M=Zn, Cu, Ni) complexes to the DNA base. Why is Zn better to bind?

The interaction of the macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane; cyclen)-coordinated divalent metals M(II) (M=Zn, Cu, Ni); M(II)–cyclen complex 1 with DNA bases has been theoretically examined by means of density functional method (B3LYP) using the model DNA bases, hypoxanthine for guanine and uracil for thymine. Both bases are bound to 1 by the charge transfer and electrostatic interactions, i.e. (i) the donation of the lone pair electron on the base-N to the metal, and (ii) the H-bond of the Cue605O oxygen of the base with the N–H unit of the cyclen ligand. The stabilization energy of both M(II)(hypoxanthine)–cyclen 3 and M(II)(uracil)–cyclen 4 complexes gave the sequence Zn>Cu>Ni, reflecting the strength of the interaction of the base-N with the metal (i) although the H-bonding (ii) is stronger with the opposite order. It was revealed that the strength of the charge transfer (i) is determined by the energy level of the unoccupied s+p hybridized σ orbital of the metal which appears by the coordination of the cyclen ligand. These results were verified by the electron flow estimated from the change in the charge distribution by binding on the cyclen ligand and on the coordinated bases. The calculations also showed that the Zn(II)–cyclen complex 1 binds more strongly to uracil in agreement with the experimental finding.

A Quantum Chemical Study of the Catalysis for Cytidine Deaminase: Contribution of the Extra Water Molecule

Cytidine deaminase is known as an important enzyme responsible for the hydrolytic deamination of cytidine, which is applied as a key step to the conversion of the precursor of the cancer drug to an active form in the living body. Cytidine with water is efficiently converted to uridine with ammonia in the cleft of cytidine deaminase. In this work, the catalysis of cytidine deaminase for the hydrolytic deamination was examined using cytosine as a model of cytidine and the model molecules for the active site of cytidine deaminase by means of the quantum chemical method. We especially investigated the contribution of the water molecule from the solvent to the catalysis, because the X-ray diffraction analysis of a crystal structure has revealed the existence of the water molecule in the vicinity of the substrate bound to the active site inside the cleft. Our computations showed that the extra water molecule from the solvent has a possibility to support the catalysis of cytidine deaminase.

An insight into the environmental effects of the pocket of the active site of the enzyme. Ab initio ONIOM-molecular dynamics (MD) study on cytosine deaminase.

We applied the ONIOM‐molecular dynamics (MD) method to cytosine deaminase to examine the environmental effects of the amino acid residues in the pocket of the active site on the substrate taking account of their thermal motion. The ab initio ONIOM‐MD simulations show that the substrate uracil is strongly perturbed by the amino acid residue Ile33, which sandwiches the uracil with His62, through the steric contact due to the thermal motion. As a result, the magnitude of the thermal oscillation of the potential energy and structure of the substrate uracil significantly increases.

Computational Study of the Effects of Steric Hindrance on Amide Bond Cleavage

The reaction mechanism of amide bond cleavages of the 2,2,6,6-tetramethylpiperidine derivatives, which proceeds in methanol solvent under mild conditions, is examined by the density functional method (B3LYP) using a model substrate. We performed the calculations to clarify the reason why the amide bond is readily broken in the present system, on the basis of an experimentally proposed proton switching pathway that is different from the generally known mechanisms. As a result, it was found that the stepwise decomposition of the amide bond by the proton switching pathway significantly lowers the energy barrier. The delocalization of the π electron in the -C(═O)-N< part is hindered by the steric effect of the four Me groups of the piperidine so that the acetyl group can easily rotate around the C-N axis and then the α-H migrates to the amide N. The subsequent amide bond dissociation, which is thought to be a rate-determining step in the experiment, was very facile. The reaction is completed by the addition of methanol to the formed ketene. Both the energy barriers of the α-H migration to the amide N and the methanol addition to ketene are largely decreased by the mediation of methanol solvent molecules. The rate-determining step of the entire reaction was found to be the α-H migration.

Dynamical behavior of the H2 molecule of the PtH(H2)[P(t-Bu)3]2(+) complex. A theory of chemical reactivity.

The dynamical behavior of the coordinated H(2) molecule of the PtH(H(2))[P(t-Bu)(3)](2)](+) complex is examined by the ONIOM-molecular dynamics (MD) method that we recently developed. The ONIOM-MD simulations reveal that the dynamical environmental effects of the t-Bu substituents of the phosphine ligands, which increase the magnitude of the energy fluctuations of the active part, significantly promote both rotation and dissociation of the coordinated H(2) molecule. The Matsubara-RRK (M-RRK) theory proposed in this study and Matsubaras equation verify that the dynamical environmental effects are crucial factors to determine the chemical reactivity.

Application of the ONIOM-Molecular Dynamics Method to the Organometallic Reaction Cis-(H)2Pt(PR3)2 → H2 + Pt(PR3)2 (R = H, Me, Ph, and t-Bu). An Insight into the Dynamical Environmental Effects

The ONIOM-molecular dynamics (MD) method, which we recently developed, is applied to one of representative organometallic reactions, cis-(H)2Pt(PR3)2 --> H2 + Pt(PR3)2(R=H, Me, Ph, and t-Bu) to give an insight into the dynamical effects of the environment on the reaction. We adopted the two-layered ONIOMmethodology and divided the system into the inner part of cis-(H)2Pt(PH3)2 and the outer part of the others.The inner and outer parts are treated by the quantum mechanics (QM) method at the HF level of theory and the molecular mechanics (MM) method with the MM3 force field, respectively. The ONIOM-MD simulations how that the thermal motion of the outer part increases the magnitude of the energy fluctuations of the inner part and promotes the H2 elimination reaction. These dynamical environmental effects increase in the order,t-Bu > Ph > Me > H, indicating that the reactivity of cis-(H)2Pt(PR3)2 increases in the same order. These results are also supported by an equation derived from the Arrhenius equation (Matsubaras equation). The snapshots of the reaction for R=t-Bu clearly indicate the new feature of the H2 elimination process

Quantum Mechanical and Molecular Dynamics Studies of the Reaction Mechanism of the Nucleophilic Substitution at the Si Atom.

The mechanism of the nucleophilic substitution at the Si atom, SiH3Cl + Cl*(-) → SiH3Cl* + Cl(-), is examined by both quantum mechanical (QM) and molecular dynamics (MD) methods. This reaction proceeds by two steps with the inversion or retention of the configuration passing through an intermediate with the trigonal bipyramid (TBP) structure, although the conventional SN2 reaction at the C atom proceeds by one step with the inversion of the configuration passing through a transition state with the TBP structure. We followed by the QM calculations all the possible paths of the substitution reaction that undergo the TBP intermediates with the cis and trans forms produced by the frontside and backside attacks of Cl(-). As a result, it was thought that TBPcis1 produced with a high probability is readily transformed to the energetically more stable TBPtrans. This fact was also shown by the MD simulations. In order to obtain more information concerning the trajectory of Cl(-) on the dissociation from TBPtrans, which we cannot clarify on the basis of the energy profile determined by the QM method, the MD simulations with and without the water solvent were conducted and analyzed in detail. The QM-MD simulations without the water solvent revealed that the dissociation of Cl(-) from TBPtrans occurs without passing through TBPcis1. The ONIOM-MD simulations with the water solvent further suggested that the thermal fluctuation of the water solvent significantly affects the oscillation of the kinetic and potential energies of the substrate to facilitate the isomerization of the TBP intermediate from the cis form to the trans form and the subsequent dissociation of Cl(-) from TBPtrans.

A proposal of the source and the evolution of the bubble in the glass melts. Molecular orbital and molecular dynamics studies

Abstract The formation of the bubble in the manufacturing process of the glass is one of the most serious problems on the production of the high quality commercial products, and the source and the evolution process of the bubble in the glass melts still remain unclear. According to our speculation that the clustered gas molecules in the glass melts grow to the bubble, we focused on the clustering of the N 2 molecules with the cations Na + , Mg 2+ , and Al 3+ included in the glass melts in the manufacturing process. Our ab initio MO (B3LYP) calculations showed that the N 2 molecules strongly bind to the cations, Na + , Mg 2+ , Al 3+ , by both electrostatic and the charge transfer interactions between the N 2 molecules and the cations. However, the binding among the N 2 molecules is extremely weak without the cations. The aggregation of the N 2 molecules at the cations was also successfully simulated in the assumed glass melts by the classical molecular dynamics method. These theoretical analyses are discussed in detail.