Hydrolysis Process of the Anticancer Agents Novel Non-classical trans-Platinum(Ⅱ) with Aliphatic Amines

The hydrolysis process of the anticancer agents novel non-classical trans- platinum(Ⅱ ) with aliphatic amines and the influence of solvent models therein have been studied by using hybrid density functional theory (B3LYP). In this study, the stepwise hydrolysis, trans- [PtCl2(Am)(isopropylamine)] + 2H2O → trans-[Pt(Am)(isopropylamine)(OH2)2]2+ + 2Cl-, was explored. Implicit solvent effects were incorporated through polarized continuum models. The stationary points on the potential energy surfaces for the first and second hydrolysis steps, proceeding via a general SN2 pathway, were fully optimized and characterized. It was found that the first hydrolysis reaction is easier than the second one and the hydrolysis of trans-[PtCl2- (isopropylamine)2] is the easiest in our studying systems. The result can assist in under-tanding the hydrolysis mechanism of trans-[PtCl2(Am)(isopropylamine)] and designing novel Pt-based anticancer drugs.     

Mechanistic Study on the Monofunctional Binding of Hydrolysis Products of Non-planar Heterocyclic Complexes Trans-[PtCl_2NH_3（piperidine）] and Trans-[PtCl_2（piperidine）_2] to DNA Purine Bases

The monofunctional substitution reactions between trans-[PtCl(H2O)(NH3)(pip)]+,trans-[Pt(H2O)2(NH3)(pip)]2+,trans-[PtCl(H2O)(pip)2]+,trans-[Pt(H2O)2(pip)2]2+ (pip = piperidine) and adenine/guanine nucleotides are explored by using B3LYP hybrid functional and IEF-PCM salvation models. For the trans-[Pt(H2O)2(NH3)(pip)]2+ and trans-[PtCl(H2O)(NH3)(pip)]+ complexes,the computed barrier heights in aqueous solution are 13.5/13.5 and 11.6/11.6 kcal/mol from trans-Pt-chloroaqua complex to trans/cis-monoadduct for adenine and guanine,and the corresponding values are 20.7/20.7 and 18.8/18.8 kcal/mol from trans-Pt-diaqua complex to trans/cis-monoadduct for adenine and guanine,respectively. For trans-[PtCl(H2O)(pip)2]+ and trans-[Pt(H2O)2(pip)2]2+,the corresponding values are 21.5/21.3 and 19.4/19.4 kcal/mol,and 26.0/26.0 and 20.7/20.8 kal/mol for adenine and guanine,respectively. Our calculations demonstrate that the barrier heights of chloroaqua are lower than the corresponding values of diaqua for adenine and guanine. In addition,the free energies of activation for guanine in aqueous solution are all smaller than that for adenine,which predicts a preference of 1.9 kcal/mol when trans-[PtCl(H2O)(NH3)(pip)]+ and trans-[Pt(H2O)2(NH3)(pip)]2+ are the active agents and ～1.9 and ～ 5.3 kcal/mol when trans-[PtCl(H2O)(pip)2]+ and trans-[Pt(H2O)2(pip)2]2+ are the active agents,respectively. For the reaction of trans-Pt-chloroaqua (or diaqua) to cis-monoadduct,we obtain the same transition-state structure as from the reaction of trans-Pt-chloroaqua (or diaqua) to trans-monoadduct,which seems that the trans-Pt-chloroaqua (or diaqua) complex can generate trans-or cis-monoadduct via the same transition-state.     

Pt/十六烷基三甲基溴化铵纳米聚集体修饰玻碳电极促进析氢(英文)

A novel, cost‐effective, and simple electrocatalyst based on a Pt‐modified glassy carbon electrode (GCE), using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant, is reported. Am‐phiphilic CTAB molecules were adsorbed on GCE by immersion in a CTAB solution. The positively charged hydrophilic layer, which consisted of small aggregates of average size less than 100 nm, was used for accumulation and complexation of [PtCl6]2? anions by immersing the electrode in K2PtCl6 solution. The modified electrode was characterized using scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, impedance spectroscopy, and electrochemical methods. The electrocatalytic activity of the Pt particles in the hydrogen evolution reaction (HER) was investigat‐ed. The results show that the CTAB surfactant enhances the electrocatalytic activity of the Pt parti‐cles in the HER in acidic solution.     

Theoretical Study on the Mechanisms of Action of Sulfurand Nitrogen-containing Amino Acid Residues with Monofunctional Guanine Adduct Formed by Antitumor Drugs trans-[PtCl2（Am）（isopropylamine）] （Am = Isopropylamine,Dimethylamine and Propylamine） and Their cis Isomers

The mechanisms of action on monofunctional guanine adducts of analogues of transplatin with aliphatic amine ligands,such as trans-[Pt（Am）（isopropylamine）（G）（H2O）] where Am represents dimethylamine,propylamine or isopropylamine and their cis isomers reacting with sulfur- and nitrogen-containing amino acid residues,were explored. Histidine and lysine residues are chosen as the model ligands of nitrogen-containing amino acid residues of proteins; meanwhile,methionine and cysteine residues are chosen as the model ligands of sulfur-containing amino acid residues of proteins. A dominating preference for sulfur-containing ligand over nitrogen-containing ligand is established. The calculated smallest activation barrier for sulfur-containing ligand is 9.9,and 21.1 kcal/mol for nitrogen-containing ligand in aqueous solution,and both of them have trans configurations. The difference in activation energy is 11.2 kcal/mol,indicating the platination of sulfur-containing amino acid residues is faster by seven to eight orders of magnitude than that of nitrogen-containing amino acid residues.     

Study on the thermal decomposition kinetics of cis/trans-[Cu(gly)_2]·H_2O

The thermal decomposition reactions of the complexes cis/trans-[Cu(gly)2]·H2O were studied by TG-DSC methods. The results showed that they have similar decomposition process, which occur in two steps. The first step is the loss of water and the second step is the decomposition of anhydrous complexes. But for cis-[Cu(gly)2]·H2O, the temperature of losing water is higher than that of trans-isomer. Their reaction mechanisms of the two-step decomposition were also proposed.     

THE STATE OF CHROMIUM (Ⅲ) ION IN AQUEOUS SOLUTION

So far few systematic studies on the hydrolytic polymerization of Cr(Ⅲ) were reported because of inertness of the ion and complication of the process. We studied it in equilibrium by pH method systematically in a wide concentration range (0.0002—0.32 M). The results show that, in the low concentration range, the composition of the polynuclear hydrolysis products may be represented as [Cr_3(OH)_4] (OH)_n (n=1,2,3); in the medium range, the composition of products as Cr[Cr(OH)_2]_n~((3+n))~+ (n=1,2,3); in the high range, the composition of products as Cr[Gr(OH)]_n~((3+2n))~+ (n=1, 2), and in the intermediate range between medium and high range where the hydrolysis system is in a transition state, the composition of products as [Cr_3(OH)_3]~(6+) and [Cr_3(OH)_4]~(5+). The values of hydrolysis constants of the identical species measured in different Cr concentration ranges and calculated by different methods were found in good agreement with each other. A predominance-arca diagram was made by using the hy     

MORPHOLOGICAL TRANSITION BETWEEN VESICLES AND TUBULES FOR A GLYCOPOLYMER-CONTAINING AMPHIPHILIC DIBLOCK COPOLYMER IN AQUEOUS SOLUTIONS*

The morphological transition of molecular assemblies in aqueous solutions for a new amphiphilic diblockcopolymer induced by changing the initial solvent conditions was studied by transmission electron microscopy (TEM). Thecopolymer was polystyrene(77)-b-poly [2 -(β-D-glucopyranosyloxy) ethyl acrylate (6)] (PSt_(77)-b-PGEA_6) and the solvent was amixture of DMF and THF. PSt_(77)-b-PGEA_6 yields vesicles and tubules when it is initially dissolved in THF and DMFrespectively. The morphological transition between vesicles and tubules can be achieved by simply varying the amounts ofTHF and DMF, or changing the temperature at which the aggregates were prepared.     

Thermal Study of [Pd(2-Phpy)Cl(L)] Complexes (L=pyridines and amines)

The complex [Pd(2-Phpy)(μ-Cl)]₂ reacts with pyridines (L=pyridine, α-picoline and γ-picoline), amines (L=isopropylamine, tert-butylamine) and ammonia to form the corresponding ortho-palladatedderivatives [Pd(2-Phpy)ClL]. The compounds have been characterized by C, H and Nanalyses and spectroscopic methods (IR and ¹H and ¹³C NMR).TG, DTG and DSC studies of the complexes were carried out in dynamic nitrogen atmosphere. From DSC analyses the heats of decomposition were calculated. The kinetics ofthe first step of thermal decomposition were evaluated from TG data by isothermal methods for L=pyridine and isopropylamine. The activation energies obtained are in the range 90–100 kJ mol^-1. The best fitting for data was observed for R2 and A1.5 kinetic models. This revised version was published online in August 2006 with corrections to the Cover Date.     

DFT Investigation on the Insertion Reaction of an Isocyanide into the（Silyl）（silylene）molybdenum Si-C Bond

The chemistry of silylene-transition-metal complexes LnM(=SiR2)SiR3 is one of the attractive synthetic targets in organometallic chemistry for such complexes are key intermediates in many transition metal-catalyzed systems.In the present work,the novel insertion reactions of an isocyanide into the Cp*Mo(CO)2(=SiMe2)(SiMe3) Si-C bond were investigated extensively by using the DFT method.The effective core potentials(ECP) with a double-ζ valence basis set(LanL2DZ) were employed for Mo and Si and the standard 6-31G basis set for all other atoms.Polarization functions[22] were added for Si(ζd = 0.262),C(ζd = 0.8) and N(ζd = 0.8).The effect of solvent was evaluated with the standard PCM model.Our calculations show that the two-step channel is energetically favorable,and the solvation mode has minor influence on the relative energies.     

Effects of Explicit and Implicit Solvent Models on the Hydrolysis Cleavage of N-Glycosidic Bond in 8-Oxo-7,8-dihydro-2?-deoxyguanosine

8-Oxoguanine(8-oxoG), a critical mutagenic DNA lesion induced by reactive oxygen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit and implicit solvent molecules on the hydrolysis cleavage of N-Glycosidic bond in 8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxo-dG) have been systematically clarified in the present work based upon two types of computational models. Detailed potential energy surface(PES) scans and full unconstraint optimizations for all the representative points on PESs were carried out at the B3LYP/6-31+G(d) level of theory. The effect of implicit solvent was tested by single-point calculation at the SCRF/IEF-PCM model. The results illustrate that the direct hydrolysis model involving one explicit water molecule can't provide a complete depiction of the hydrolysis process of 8-oxo-dG, attributed to the insufficiency of nucleophile activation and leaving group stabilization. The expansion hydrolysis model involving four explicit water molecules, however, facilitates discrete proton transfer and therefore produces smooth reaction surfaces for both the dissociative(SN1) and concerted(SN2) pathways. The presence of the implicit solvent substantially lowers all activation energies and the SN1 process is more favorable than the SN2 process. The data and insights present here agree well with the experimental results and have given out a baseline for the enzymatic deglycosylation reaction of 8-oxo-dG.     

ESR spectra studies of Cu(Ⅱ) 2,4-dihydroxybenzaldehyde tyrosine complex

A novel Schiff base derived from 2,4-dihydroxybenzaldehyde and tyrosine and its copper(Ⅱ)complex have been synthesized and characterized.The composition of the complex is K[CuL] H2O,where L=H11C16NO5.ESR spectra of the copper(Ⅱ)complex were investigated at different temperatures and in various solvents.The second order effect and the relaxation effect were observed in the solution spectrum at room temperature,which was satisfactorily explained by spin Hamiltonian.The bonding parameters of copper(Ⅱ)complex were calculated using spectral parameters from ESR spectra at low temperature.Its bonding characterization and stability were disscussed.The result shows that the in-plane a-bond and the in-plane π-bond in the complex all play an important role.     

Theoretical Study of Interaction between Apalutamide Anticancer Drug and Thymine by DFT Method

The main purpose of this study is a better comprehension of the non-bonded interaction between an anticancer drug apalutamide and deoxyribonucleic acid(DNA). In the present work, the interaction between anticancer drug apalutamide and one of the DNA bases called 2'-deoxythymidine 5'-monophosphate(thymine) by Density Functional Theory(DFT) calculations in the solvent water has been investigated for the first time. The non-bonded interaction effects of the molecule apalutamide with thymine on the electronic properties, chemical shift tensors and natural charges have been also detected. The natural bond orbital(NBO) analysis was performed for determining the role of electron donor and acceptor of the molecules apalutamide and thymine at the complex thymine/apalutamide. Both Electron location function(ELF), localized orbital locator(LOL) and quantum theory of atoms in molecules(QTAIM) analysis were carried out in order to determine the chemical bond nature in the investigated compounds. The values of ELF and LOL parameters for the selected bonds are small, which confirms the non-covalent character of these bonds in nature. The electronic spectra of the apalutamide drug, thymine and complex thymine/apalutamide in solvent water were calculated by Time Dependent Density Functional Theory(TD-DFT) for the investigation of interaction effect; Non-bonded interaction between the compound apalutamide and thymine has changed the value of λmax.     

Two Zinc(Ⅱ) Complexes Based on 7rany-(1R,2R)-cyclohexanediamine: Molecular Structure Analyses and Preparation of Composite Membrane

Two novel complexes Zn2(chda)2(TPA)Cl2(1) and [Zn(chda)2(H2O)2](TPAXH2O)2(2)[chda is a chiral ligand of trans-(1R,2R)-cyclohexanediamine, H2TPA is terephthalic acid] were synthesized at room temperature. The molecular structures of complexes 1 and 2 were identified by single-crystal X-ray diffraction measurement. The results showed that complex 1 had a binuclear structure, each Zn(Ⅱ) ion was four coordinated by two N atoms of chda, one O atom of TPA and one Cl atom, to construct a distorted tetrahedral geometry. For complex 2, the Zn(Ⅱ) ion was six coordinated by two chda molecules and two water molecules to form a ZnN4O2 octahedral geometry. Complexes 1 and 2 further extended into three-dimensional supramolecular frameworks by hydrogen-bonding interactions. Hirshfeld surface analysis and fingerprint plots were used to further analyze the contribution of diflerent intermolecular interactions. Further, a composite membrane [Zn(chda)2(H2O)2](TPA)(H2O)2/CA was prepared by adding 10%(mass fraction) of complex 2 into cellulose acetate using acetone/chloroform( V:V-1:1) as solvent.     

A series of novel Zn(Ⅱ) and Mn(Ⅱ) metal-organic frameworks constructed by 2,4-bis-oxyacetate-benzoic acid: syntheses,structures and photoluminescence

A new carboxylic acid ligand, 2,4-bis-oxyacetate-benzoic acid(H3BOABA), was designed and introduced to construct novel metal-organic framework materials. [Zn Na(BOABA)(phen)(H2O)]·H2O(1), Zn Na(BOABA)(2), Mn3(BOABA)2(phen)2(3), [Mn2(BOABA)(OH)]·(H2O)2(4)(CCDC: 885138, 885137, 894225, 883094) were hydrothermally synthesized and characterized by elemental analysis, IR spectra and thermal gravimetric analyses. Crystal structures of the complexes were determined by single crystal X-ray diffraction method. Complex 1 is a one dimensional double edges non-interpenetrated framework decorated by the phen ligands on the surface. Complex 2 is an unique three dimensional open framework, consisting of Zn(II) and Na(I). Complex 3 is an unique double edges one dimensional MOF containing a [Mn3(BOABA)2(phen)2]n non-interpenetrated structure. Complex 4 is a two dimensional plane structure containing two Mn atoms in the same coordination environment. The interaction between four complexes and DNA were studied by Et Br fluorescence probe. Meanwhile, photoluminescence studies revealed that these four complexes display strong fluorescent emission bands in the solid state at room temperature.     

Investigation of Hydrolysis in Poly（ethylene terephthalate） by FTIR-ATR

The hydrothermal aging of poly(ethylene terephthalate)(PET) was investigated at 70 95 °C. A new method to investigate the hydrolysis degree of PET by Fourier transform infrared spectroscopy(FTIR) was proposed. The spectra during the hydrothermal aging were measured using attenuated total reflection accessory(ATR). Peak resolving of carbonyl regions was performed, and the ratio of two groups of bands representing carboxylic acids and esters respectively were calculated to show the hydrolysis degree of ester groups in PET. The acid/ester ratio shows exactly the same trend as the average chain scission number per unit mass at various temperatures and thus can be used as a parameter to characterize the hydrolysis and random chain scission of PET. This method related to the hydrolysis mechanism directly, is simple, fast and convenient compared to the traditional methods such as viscometry, end-group titration and size exclusion chromatography(SEC). It may also be useful in hydrolysis characterization of other polyesters.     

4,5,6,7-Tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine as a new scaffold for heat shock protein 90 inhibitors

Heat shock protein 90(hsp90) is a promising anticancer drug target. A library of 2,4-dihydroxyphenyl(resorcinol) substituted 4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine compounds that target this protein were designed and prepared based on our earlier study. The compounds were tested in five cancer cell lines and seven of them showed notable anticancer activity(IC_(50)2–10 mmol/L). The active subset compounds were further subjected to a polarized fluorescent assay and exhibited high binding affinity toward purified hsp90(IC_(50)60–100 nmol/L). These results indicated that the tetrahydrotriazolopyrazine motif of the molecules may represent a novel scaffold for the development of hsp90 inhibitors.     

Synthesis of 2-[2H]-2-(1-methylalkyl)succinic acids

We describe a specific procedure for the synthesis of deuterium-labelled 2-(1-methylalkyl)succinate established via alkylation of diethyl malonate,Krapcho decarboxylation reaction with D_2O and hydrolysis reaction.Two novel compounds,2-[~2H]-2-ethylsuccinic acid and 2-[~2H]-2-(1-methylheptyl)succinic acid were prepared via this synthetic route and characterized by mass spectrometry and 'H NMR.The results showed that the 2-(1-methylalkyl)succinic acids were deuterated at the β-position,which is considered as an important reaction centre in the anaerobic degradation of n-alkanes.     

Cationic ring-opening polymerization of 3,3-bis（chloromethyl）oxacyclobutane in ionic liquids

Cationic ring-opening polymerization of 3,3-bis(chloromethyl)oxacyclobutane catalyzed by BF_3·OEt_2 was carried out in ionic liquids [bmim]BF_4 and [bmim]PF_6.The influences of BCMO concentration and molar ratio of BCMO/BF_3·OEt_2 on the molecular weights and yield of PBCMO were investigated.The polymerization in ionic liquids proceed to high conversions,although molecular weights are limited,similar to polymerization in organic solvent such as CH_2Cl_2.Follow a viewpoint of green chemistry, we feel ionic liquid [bmim]BF_4 is superior to [bmim]PF_6.Extracting [bmim]PF_6 from the product using organic solvent as extractant limits its advantage as a green reaction media.     

Studies on PNPP Hydrolysis Catalyzed by Schiff Base Cobalt（Ⅱ） Complexes Containing Benzoaza-15-crown-5

Three novel Schiff base cobalt（Ⅱ） complexes containing benzoaza-15-crown-5, CoL^1, CoL^2 and CoL^3 were synthesized and characterized, and these complexes were used in catalytic hydrolysis of carboxylic ester （PNPP, p-nitrophenyl picolinate） as mimic hydrolytic metalloenzyme. The analysis of specific absorption spectra of the hydrolytic reaction systems indicated that the catalytic hydrolysis involved the key intermediates formed by PNPP with cobalt（Ⅱ） complexes. The CoL^3 bearing the electron withdrawing group shows better catalytic activity due to its stabilization effect on active species MLS^-. The catalytic mechanism of PNPP hydrolysis was also proposed. The kinetic parameter of PNPP catalytic hydrolysis has been calculated and the activation energy for the catalytic hydrolysis is 43.69, 39.76 and 35.44 kJ·mol^-1, respectively.     

Influences of Synthesis Conditions on the Formation of Methotrexate Intercalated Layered Double Hydroxides by Exfoliation-reassembly Route

The intercalation of methotrexate(MTX) into layered double hydroxides(LDHs) via an exfoliation-reassembly process was performed and the resulting hybrids were then characterized by X-ray difEractiometry( XRD), Fourier transform infrared(FTIR) spectroscopy, thermogravimetry(TG) and differential scanning calorimetry(DSC), etc. In the synthesis procedure, LDHs particles were firstly delaminated, and the reassembly process was performed to get MTX intercalated LDH(MTX/LDHs) hybrids. Tlie reassembly conditions, such as reassembly time and diflerent reassembly solvent, were studied emphatically. It was fbimd that 20 min is the optimum time and formamide is the most suitable solvent in the reassembly process. At last, the controlled release property and the drug-loading capacity were examined emphatically to reveal that MTX/LDHs hybrids reassembled in fomiamide exhibit the highest drug-loading capacity. The cytotoxicity of the hybrids was estimated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-/7-tetrazolium bromide, thiazolyl blue tetrazolium bromide(MTT) assays on the human lung cancer cells(A549), with the results showing that MTX/LDHs hybrids have effective suppress role on the proliferation of cancer cells, and tlie hybrids obtained from the formamide solution present much better anticancer efleet than the other samples.