The Antiepileptic Lamotrigine and Its Analogues: Comparative Theoretical Electronic Properties

Electronic properties of lamotrigine (LTG) and two analogues (A1 and A2) are compared through MOPAC-AM1 calculations. Two stable conformers of LTG are calculated to exist in agreement with X-ray crystallography. In the three compounds and the two conformers for each of them, the more favorable protonation sites are N₂ and N₄; these should then be the sites appropriate for interaction with a receptor, and group valence reinforces the supposition. The molecular electrostatic potentials show that a region between the two chlorine atoms in LTG could be the site for an electrostatic interaction with a corresponding site in the receptor. The fluorine atom in A1 would play an equivalent role. A simple model for LTG-receptor interaction is proposed.     

射频磁控溅射CNx薄膜的结构与衬底温度关系的研究

使用射频磁控溅射方法在不同衬底温度下（ts=室温，350，500℃）于Si(001)衬底上沉积了CNx膜，并利用拉曼（Raman)光谱、傅里叶变换红外光谱（FTIR）及X射线衍射光电子能谱（XPS）对CNx膜的化学结合状态与温度的关系进行了研究。Raman光谱结果表明，随衬底温度（ts) 增加，D带向低频方向移动，G带向高频方向移动；它们的半高宽分别由375和150cm^-1减小至328和142cm^-1；ID／IG由3．76减小至2.88。FTIR谱中除无序D带（1400cm^-1)和石墨G带（1570cm^-1)外，还有－700cm^-1,～2210cm^-1(C=N),2330cm^-1(C-O)及3255－3351cm^-1(N-H)等峰。XPS测试结果表明：随衬底温度增加，N与C的物质的量比由0.49下降至0.38，sp^2(C-N)组分与sp^3(C-N)组分强度比呈增大趋势。低温（350℃）退火并未对CNx膜的化学结合状态产生较大影响；高温（900℃）退火样品则显示出较好的结晶化程度。     

Intramolecular proton transfer induced by divalent alkali earth metal cation in the gas state

Interactions between divalent alkali earth metal (DAEM) ions M (M?Be, Mg, Ca, Sr, Ba) and the second stable glycine conformer in the gas phase, which can transfer into the ground‐state glycine‐M²⁺ (except the glycine–Be²⁺) among each corresponding isomers when these divalent metal ions are bound, are studied at the hybrid three‐parameter B3LYP level with three different basis sets. Proton transfers from the hydroxyl to the amino nitrogen of the glycine without energy barriers have been first observed in the gas phase in these glycine–M²⁺ systems. The interaction between the glycine and these DAEM ions except beryllium and magnesium ion only create an amino hydrogen pointing to the original hydroxyl due to their weaker interaction relative to those divalent transition metal (DTM) ion‐bound glycine derivatives, being obviously different from that between the glycine and DTM ions, in which two amino hydrogens point to the original hydroxyl oxygen when these metal‐chelated glycine derivatives are produced. The interaction energy between the glycine and divalent magnesium would be the boundary of one or two amino hydrogens pointing to the hydrogyl oxygen, i.e., the ?170.3 kcal/mol of binding energy is a critical point. Similar intramolecular proton transfer has also been predicted for those DTM ion‐chelated glycine systems; however, that in the gas state has not been observed in the monovalent metal ion‐coordinated glycine systems. The binding energy between some monovalent TM ion and the glycine is similar to that of the glycine–Ba²⁺, which has the lowest binding strength among these DAEM–ion chelated glycine complexes. The difference among them only lies in the larger electrostatic and polarized effects in the latter, which favor the stability of the zwitterionic glycine form in the gas phase. According to these observations, we predict that the zwitterionic glycine would exist in the field of two positive charges in the gas phase. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 205–214, 2003     

(BN)_n团簇的结构和稳定性

用HF方法、密度泛函理论的B3LYP以及微扰理论的MP2方法 ,在 6 3 1G(d)基组水平上 ,对 (BN) n(n =1～ 16)团簇的各种可能结构进行了优化 .讨论了环状与笼状稳定团簇的几何构型、自然键轨道 (NBO)、振动频率、结合能、核独立化学位移 (NICS)和能量二次差分 ,得到了 (BN) n(n =1～ 16)团簇结构的稳定性信息 .比较了HF ,B3LYP以及MP2三种理论方法对(BN) n 团簇的适应性所表现出的差异 .     

Novel design of a pentacyclic scaffold as structural mimic of saframycin A

The design, synthesis and evaluation of a pentacyclic scaffold, CWO-324 to mimic saframycin A is described. CWO-324 is readily synthesized in five steps from 1,4-diacetyl-piperazine-2,5-dione and 2,5-dimethoxybenzaldehyde. CWO-324 was found to scission DNA, binds to bases 69-83(5′-GCAGTCAGG CACCGT-3′) of Hind III/Rsa I from plasmid pBR322 DNA in a foot-printing study and possesses anti-tumor activity.     

Anion control of isomerism, crystal packing and binding properties in a mononuclear zinc complex

The coordination chemistry of the tetradentate pyridyl N-donor ligand cis-3,5-bis-[2-pyridinyleneamin]-trans-hydroxycyclohexane (DDOP) has been investigated with zinc(II) nitrate and triflate. The resulting complexes, [Zn(DDOP)(H₂O)(NO₃)](NO₃) (1), and [Zn(DDOP)(H₂O)(OTf)](OTf) (2) differ not only in their counterions, but also the arrangement of the axial ligands and their solid state hydrogen bonded networks. Isothermal titration calorimetry was used to assess the difference in binding properties exhibited by the two zinc complexes at physiological pH in an aqueous environment. A series of coordinating amino acids were found to preferentially bind to the mononuclear zinc triflate (1) complex over the corresponding nitrate (2) assembly, with histidine exhibiting a two centre binding mode.     

The importance of nonconventional structures in the binding of Ni<Superscript>+</Superscript> to ethynylsilanes and ethynylgermanes

The influence of the nature of the heteroatom on the Ni⁺ gas-phase binding energies of HCC–XH₃ (X is C, Si, or Ge) compounds has been investigated through the use of high-level density functional theory methods. The structures of the corresponding Ni⁺ complexes were optimized at the B3LYP/6-311G(d,p) level of theory. Final energies were obtained in single-point B3LYP/6-311+G(2df,2p) calculations. Nonconventional complexes, in which the metal cation interacts simultaneously with the CC system and with one of the X–H bonds of the substituent XH₃ group, play a significant role in the binding of Ni⁺ to HCC–XH₃ (X is Si or Ge) derivatives. Conversely, such nonconventional complexes are not local minima of the propyne–Ni⁺ potential-energy surface. This establishes a clear distinction between unsaturated carbon derivatives and the Si- and Ge-containing analogues as far as bonding to transition-metal monocations is concerned. Actually, the attachment of Ni⁺ to HCC–XH₃ (X is Si or Ge) compounds in the gas phase yields a mixture of conventional and nonconventional complexes. These agostic-type interactions can be viewed as a dative bond from the X–H bonding orbital toward the empty s orbital of the metal, and a back-donation from the valence electron pairs of the metal into the X–H antibonding orbital of the neutral species.Proceedings of the 11th International Congress of Quantum Chemistry satellite meeting in honor of Jean-Louis Rivail     

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin

Summary The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3R-compounds possess notable Gram-positive antibacterial activity and potent-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain-lactamase inhibitory activity.Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3R, and 3S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3R and the 3S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains ofboth the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, bioactive conformer for the classical-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S₂-subsite, specific for the side-chain aromatic moiety, and the 3-carboxylate functionality is presented.This work has been reported in preliminary form at the 4th Royal Society of Chemistry International Symposium on Recent Advances in the Chemistry of-lactam Antibiotics, Churchill College, Cambridge, U.K., 3–6 July 1988.     

Detection of potential membrane receptor proteins concerning circadian rhythmic leaf movement of legumes using novel photoaffinity probe compounds

Circadian rhythmic plant leaf movement, called nyctinasty, is controlled by a time-course change in the internal concentration of the leaf-movement factor in the plant body. We report that specific binding protein (210 and 180 kDa) for a leaf-movement factor, potassium lespedezate, is contained in the plasma membrane of the plant motor cell. These proteins would be potential receptors for leaf-movement factor to control the leaf movement.     

Chemical reaction dynamics of PeCB and TCDD decomposition: A tight‐binding quantum chemical molecular dynamics study with first‐principles parameterization

The decomposition reaction dynamics of 2,3,4,4′,5‐penta‐chlorinated biphenyl (2,3,4,4′,5‐PeCB), 3,3′,4,4′,5‐penta‐chlorinated biphenyl (3,3′,4,4′,5‐PeCB), and 2,3,7,8‐tetra‐chlorinated dibenzo‐p‐dioxin (2,3,7,8‐TCDD) was clarified for the first time at atomic and electronic levels, using our novel tight‐binding quantum chemical molecular dynamics method with first‐principles parameterization. The calculation speed of our new method is over 5000 times faster than that of the conventional first‐principles molecular dynamics method. We confirmed that the structure, energy, and electronic states of the above molecules calculated by our new method are quantitatively consistent with those by first‐principles calculations. After the confirmation of our methodology, we investigated the decomposition reaction dynamics of the above molecules and the calculated dynamic behaviors indicate that the oxidation of the 2,3,4,4′,5‐PeCB, 3,3′,4,4′,5‐PeCB, and 2,3,7,8‐TCDD proceeds through an epoxide intermediate, which is in good agreement with the previous experimental reports and consistent with our static density functional theory calculations. These results proved that our new tight‐binding quantum chemical molecular dynamics method with first‐principles parameterization is an effective tool to clarify the chemical reaction dynamics at reaction temperatures. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005