Shou-Rong Zhu

Dinuclear palladium(II) complexes containing two monofunctional [Pd(en)(pyridine)Cl]+ units bridged by Se or S. Synthesis, characterization, cytotoxicity and kinetic studies of DNA-binding

Two novel dinuclear palladium(II) complexes, ¿[Pd(en)Cl]2(bpse)¿(NO3)2 (1) and ¿[Pd(en)Cl]2 (bpsu)¿(NO3)2 (2), (where en is ethylenediamine; bpse is bis(3-methyl-4-pyridyl) selenide; bpsu is bis(3-methyl-4-pyridyl) sulfide) have been synthesized. The complexes have been characterized by elemental analysis, IR, 1H NMR, and 13C NMR. They have been assayed for antitumor activity in vitro against the mice leukemia L1210 and the human coloadenocarcinoma HCT8 cell lines. The results show that compound 1 has a lower I.D.50 value against the two cancer cell lines as compared to compound 2; the compounds also shows a lower I.D.50 value than cisplatin against the HCT8 cell line, but a higher I.D.50 value than cisplatin against the L1210 cell line. Binding studies indicate that compound 1 possibly interacts with DNA by a nonintercalative mode. Kinetics of binding of the two compounds to DNA are firstly studied using ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer under pseudo-first-order condition. The stronger binding of two steps in the process of the compounds interacting with DNA are observed, and the Kobs and Ea of binding of the two steps (where Kobs is the observed pseudo-first-order rate constant, Ea is the observed energy of activation) are obtained.

Ethylenediamine-palladium(II) complexes with pyridine and its derivatives: synthesis, molecular structure and initial antitumor studies.

The synthesis of four mononuclear palladium complexes of general formula [Pd(en)Cl(L)]NO3 (en = ethylenediamine; L = pyridine (I), 4-methylpyridine (II), 4-hydroxypyridine (III) or 4-aminopyridine (IV) has been achieved. The structure of these compounds was studied by elemental analysis, IR, far-IR and 1H NMR; complex I was analyzed by X-ray diffraction. The crystal of [Pd(en)(pyridine)Cl]NO3 is monoclinic, space group P21/c (a = 7.990(2), b = 16.058(3), c = 9.846(2) A, beta = 103.81(3) degrees, Z = 4, R = 0.067, Rw = 0.066). The Pd(II) atom exhibits an approximately square planar coordination with bond lengths in the range 2.017-2.042 A for Pd-N and 2.320 A for Pd-Cl. In order to determine the donor strength of the aromatic pyridine ligands, the stability constants of binary complex ML2+ (M = [Pd(en) (H2O)2]2+; L = pyridine, 4-Me-pyridine, 4-OH-pyridine and 4-NH2-pyridine) were determined by potentiometric pH titration in aqueous solution (T = 25 degrees C, I = 0.1 mol l-1 NaNO3). The results show that the stability constants of the binary complexes systematically increase with increasing pKa of the pyridines. The above four palladium complexes, [Pt(en)(pyridine)Cl]NO3 and cis-diamminedichloroplatinum (II) (cis-DDP) were assayed for cytotoxicity in vitro against the human leukemia cell line HL-60, and compounds I, II, III and cis-DDP show significant cytotoxic activity against HL-60.

Kinetics and mechanism of carboxyester hydrolysis using Zn(II) complexes with functionalized phenanthroline complexes

Abstract Zinc(II) complexes of six new functionalized phenanthrolines have been examined as catalysts for the hydrolysis of 4-nitrophenyl acetate (NA). The new ligands form a 1:1 zinc complex in the pH range 6.5–9.0. In the kinetic studies using the zinc complexes in 10% (v/v) CH3CN at 298 K, I=0.10 mol dm−3 KNO3 and pH 6.8–9.0, it was shown than an axial OH− serves as a good nucleophile that effectively catalyzes NA hydrolysis. The hydrolysis rate follows the law v=(kplus[complex]+kOH[OH−]+ko)[NA]. The second-order rate constants of ZnLH−1 are 0.934, 0.420, 0.360, 0.307, 0.257 and 0.143 mol−1 dm3 s−1 for L1, L2, L3, L4, L5 and L6, respectively, obviously larger than the corresponding value of 0.047 mol−1 dm3 s−1 for the N-methylcyclen-Zn(II)OH− complex catalyst.

The different roles of metal ions and water molecules in the recognition and catalyzed hydrolysis of ATP by phenanthroline-containing polyamines

The phenanthroline bridging polyaza ligands L1, L2 and L3 can selectively and strongly bind nucleotides at physiological pH, and hence accelerate the hydrolysis rate of the bound ATP. It is interesting that a phosphoramidate intermediate at 2.88 ppm (should be added 5.63 ppm when compared with other models) was found in the hydrolysis process of L/ATP. By introduction of metal ions (critical Zn(2+) or hard Mg(2+), Ca(2+)) to the L/ATP system, recognition of the anionic substrates by the protonated ligands was greatly promoted. However, due to the different affinities of metal ions to the receptor and the substrate, ATP hydrolysis in Zn(2+)/L/ATP system and Mg(2+)(Ca(2+))/L/ATP system occurs through different mechanisms. By comparison with the M/ATP (M=Zn(2+), Mg(2+), Ca(2+)) system, the rates of ATP-hydrolysis in the Mg(2+)Ca(2+)/L/ATP system and the Zn(2+)/L/ATP system were enhanced and retarded, respectively. Moreover, the reasons contributing to large rate range of the L/ATP systems and M(2+)/L/ATP systems were given. The results show that metal ions vertically regulate the recognition and hydrolysis of ATP. On the other hand, water molecule participates in the hydrolysis reactions at different steps with different functions in the L/ATP systems and M(Zn(2+), Mg(2+), Ca(2+))L/ATP systems.

Studies of artificial hydrolytic metalloenzymes: the catalytic carboxyester hydrolysis by new macrocyclic polyamine zinc(II) complexes with a phenolic-pendant as novel nucleophile

Abstract Zinc(II) complexes of new macrocyclic tetraamines (cyclam derivatives) having a strategically appended phenolic group, 6-(2′-hydroxy)-benzyl-1,4,8,11-tetraazacyclotetradecane (LA), 6-(2′-hydroxy-5′-bromo)-benzyl-1,4,8,11- tetraazacyclotetradecane (LB) and 6-(2′-hydroxy-3′,5′-dibromo)-benzyl-1,4,8,11-tetraazacyclotetradecane (LC), have been examined as catalysts for the hydrolyses of 4-nitrophenylacetate (NA). The phenolic functionalized macrocycles from 1:1 ZnL complexes at pH ca 5. The potentiometric pH titration of LA, LB and LCZnII complexes showed dissociation of a phenolic proton with pKa values of 8,8, 8.7 and 8.5 at 298 K and I = 0.10 mol.l−1 KNO3 for LA, LB and LCZnII complexes respectively. In the kinetic studies using the zinc complex in 10% (v/v) CH3CN at 298 K, I = 0.10 mol.l−1 KNO3 and pH 7.0–9.5, we proved that the coordinated phenolate can serve as a good nucleophile that effectively catalyzes NA hydrolysis. The hydrolysis rate follows the law v = (kcat[complex]+KOH[OH−]+k0[NA]. The pH rate profile gave a sigmoidal curve with inflection points at pH 8.8, 8.7 and 8.6 for LA, LB and LC, respectively, which correspond to the pKa value of the complex. The second-order (first-order each in complex and NA) rate constants are 0.056, 0.084 and 0.127 mol.l−1. s−1 for LA, LB and LC are obviously larger than the corresponding value of 0.047 mol.l−1. s−1 for N-methylcyclen-Zn(II)-OH− complex catalyst. This is, to our knowledge, the first phenolate coordinated zinc complex that efficiently catalyses the hydrolysis of 4-nitrophenyl acetate (NA). The present study also proves that solvolysis of NA (i.e. water attack on the ester) does exist, but the reaction rate (k0 = 1.12 × 10−5 s−1) is rather small.

Study of kinetics and mechanism of the acid dissociation of copper(II) complex of novel C-functionalized macrocyclic dioxotetraamines

Abstract The kinetics of the acid dissociation of copper(II) complex of a novel C-functionalized macrocyclic dioxotetraamine has been studied using a stopped-flow spectrophotometer. It was provent that substituents decrease the acid dissociation rates. The dissociation rate follows the law vd = CcomkK1K2H2/(1 + K1H + K1K2H2). On the intermediates we have obtained, the dissociation kinetics are interpreted by a mechanism involving the negatively charged carbonyl oxygen of the complex being rapidly protonated in pre-equilibrium step, the rate-determining step being intramolecular hydrogen (enolic tautomer) migration (to imine nitrogen). The dissociation rate reached a plateau in strongly acidic solution. By means of temperature coefficient method, K1, K2 of the pre-equilibrium step and ΔH≠ and ΔS≠ of the rate-determining step were obtained and the results discussed. It is the strong in-plane ligand field that increased ΔH of the rate-determining step and thus decreases the dissociation rate constant. The Bronsted type linear free energy relationships do exist in this C-functionalized dioxotetraamine copper(II) complex. The results clarify insights into acid dissociation mechanisms for the 14-membered macrocyclic dioxotetraamine copper(II) complex.

Thermodynamic studies on supramolecular interactions of metal ions with nucleotides/tripods ligands

Abstract Four closely related polyamino tripodal ligands 1,3,5-tri(n-2′,5′-diaminohexane)-benzene (L1), 1,3,5-tri(n-2′,5′-diaminoheptane)-benzene (L2), 1,3,5-tri(n-2′,5′-diaminooctane)-benzene (L3) and 1,3,5-tri(n-2′,5′-diaminononane)-benzene (L4) were synthesized and characterized. Each tripodal ligand forms six protonated species in solution. The binding of these tripodal ligands to the nucleotide anions ATP, ADP and AMP are described in detail, with equilibrium constants given for each species formed. The strength of binding increases with the number of protons, corresponding to an increase in the number of hydrogen bonds and to an increase in the coulombic attractive forces. Moreover, the existence of a benzene spacer takes π-stacking interactions with the nucleobase residue of the nucleotides. At the same time, the coordination properties of the ternary complexes formed from the above tripods and Zn(II) and ATP were studied. The metal complexes of tripods recognize the nucleotides via multiple interactions that are similar to those occurring in the center of enzymes.

Studies of artificial hydrolytic metalloenzymes: The catalyzed carboxyester hydrolysis by copper(II), zinc(II) and cobalt(II) complexes of the tripod ligand tris(2-benzimidazylmethyl)amine

The hydrolysis kinetics of p-nitrophenyl acetate (NA) catalyzed by CuII, ZnII and CoII complexes of tris(2-benzimidazylmethyl)amine (NBT) have been studied. The hydrolysis rate is first-order in both metal(II) complex and NA. The second-order rate constants, kcat are 0.083, 0.241 and 0.285 mol−1Ls−1 (298 K, I = 0.10 molL−1 KNO3, 0.02 molL−1 tris buffer, 40% MeCN aqueous solution) for Zn–NBT, Co–NBT and Cu–NBT complexes, respectively. The result indicates that the hydrolytic metalloenzyme activity of different metal complexes increases with the electrophilicity of the metal ions and that the complexes, in this paper, constitute that most efficient hydrolytic metalloenzyme models reported to date. An increase in MeCN content in the solution greatly reduces the hydrolytic activity of the nucleophiles.

Crystal structures and physico-chemical properties of two new one-dimensional Zinc(II) complexes with sulfide bridging bispyridines

Abstract 4,4′-Dipyridyl sulfide ( L 1 ) and 4,4′-di(3-methyl)pyridyl ( L 2 ) sulfide coordination compounds of the general formula Zn( L )(X) 2 ( L 1 =4,4′-dipyridyl sulfide; L 2 =4,4′-di(3-methyl)pyridyl sulfide; X=CH 3 COO − , Cl − ), have been obtained. The compounds were characterized by single crystal X-ray diffraction, elemental analysis, IR and 1 H NMR. Both compounds are of one-dimensional coordination polymers and crystallize in the orthorhombic systems, while in different space groups with Pnc 2 for [Zn L 1 (CH 3 COO) 2 ] 1 and Pna 2(1) for [Zn L 2 Cl 2 ] 2 , respectively. X-ray analysis and 1 H NMR experiments indicate that variation of ligands rather than counter anions, CH 3 COO − and Cl − , leads to the change in the modes of the dimensionality array, that is, complexes 1 prefers a linear coordination fashion while complexes 2 exhibits a zigzag conformation.

Studies on the formation and decomposition of copper(III) and nickel(III) complexes with macrocyclic ligands containing amide groups

Abstract The spectral characteristics of 13- and 14-membered C-functionalized macrocyclic dioxotetraamine and the corresponding saturated polyamine copper(II), copper(III) and nickel(III) complexes have been studied. It was shown that C-functionalized substituents, although not coordinating to the metal ion, have significant effects on the spectral properties of their MIII complexes. As for copper(II) complexes, substituents increase the in-plane ligand field and decrease the wavelength of the d-d absorption of their complexes. Substituents increase the π-CT wavelength and decrease the absorption coefficients. Rate constants and activation parameters for the oxidation of CuII complexes by peroxodisulfate and decomposition reactions of copper(III) complexes in aqueous solution were also measured. Activation parameters were shown to be dependent on ligand structure.