林华宽
从事溶液配位物理化学研究,擅长溶液配位反应热力学、动力学、热化学研究。研究内容包括模拟梅、抗癌药物、阴离子识别。
个性化签名
- 姓名:林华宽
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学术头衔:
博士生导师
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学科领域:
物理化学
- 研究兴趣:从事溶液配位物理化学研究,擅长溶液配位反应热力学、动力学、热化学研究。研究内容包括模拟梅、抗癌药物、阴离子识别。
林华宽1962年9月-1968年9月南京大学化学系本科生,1968年10月-1978年10月山东省化学研究所(原中国科学院济南化学研究所)从事色谱、催化研究,1978年10月-1981年7月南开大学化学系硕士研究生,1982年1月-1984年12月南开大学化学系博士研究生,1985年1月-1987年5月南开大学化学系讲师,1987年5月-1993年12月南开大学化学系副教授,1993年12月-现在南开大学化学系教授。1994年被国务院学位委员会遴选为博士生指导教师。1990年7月-1991年7月美国Oklahoma大学化学系博士后研究。1991年被国务院学位委员会和原国家教育委员会授予“对社会主义建设做出突出贡献的中国博士学位获得者“。1993年获国务院政府特殊津贴。1985年7月“络合物化学中的线性热力学函数关系”获原国家教育委员会科技进步奖贰等奖,1991年5月“溶液配位化学中热力学和动力学研究“获原国家教育委员会科技进步奖贰等奖。自1978年起从事溶液配位物理化学研究,擅长溶液配位反应热力学、动力学、热化学研究。研究内容包括模拟梅、抗癌药物、阴离子识别。在国内外重要核心期刊上发表论文230多篇。现为国际抗癌药物期刊“Anti-Cancer Agents in Medicinal Chemistry”, ”Recent-Patents on Anti-Cancer Drug Discovery” Editorial Advisory Board成员。
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成果数
17
林华宽, Feng-Hua Lia, Guang-Hua Zhaoa, c, , Hong-Xing Wua, Hai Linb, Xiang-Xia Wua, Shou-Rong Zhua, Hua-Kuan Lina, *
Journal of Inorganic Biochemistry 100(2006)36-43,-0001,():
-1年11月30日
Two novel lanthanum (III) complexes containing 2-methylene–1,10-phenanthroline units bridged by aliphatic diamines were synthesized and characterized by elemental analysis, IR, NMR, thermal analysis and conductance measurements. They have been assayed for anticancer activity in vitro against HL-60 (human leukocytoma) cells, PC-3MIE8 (human prostate carcinoma) cells, BGC-823 (human stomach carcinoma) cells, MDA-MB-435 (human galactophore carcinoma) cells, Bel-7402 (human liver carcinoma) cells, and Hela (human cervix carcinoma) cells. The results show that the two complexes exhibit good cytotoxic activities against different cell lines in general, especially more effective than cisplatin against Bel-7402, BGC-823 and MDA-MB-435 cell lines. DNA-binding studies indicate that, besides the intercalation, the complexes bind to DNA by the other interaction(s), which might be responsible for the production of more compact DNA, coinciding with more A-like feature of DNA as suggested by CD spectra.
Lanthanum (, III), , 1,, 10-Phenanthroline, Cytotoxic activity, DNA-binding
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林华宽, Guanghua Zhao, Huakuan Lin*, Shourong Zhu, Hongwei Sun, Yunti Chen
Journal of Inorganic Biochemistry 70(1998)219-226,-0001,():
-1年11月30日
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.
Dinuclear palladium complexes, Bis (, 3-methyl-4-pyridyl), selenide or sulfide, DNA-binding kinetics, Stopped-flow spectrophotometer, Cytotoxicity
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林华宽, Guanghua Zhao , Hongwei Sun, Huakuan Lin*, Shourong Zhu, Xuncheng Su, Yunti Chen
Journal of Inorganic Biochemistry 72(1998)173-177,-0001,():
-1年11月30日
Five new tetradentate ligands and their corresponding palladium complexes, [Pd(L)]Cl2 (L =N,N'-dimethyl-1,10-phenanthroline-2,9-dimathanamine, N,N'-diethyl-1,10-phenanthroline-2,9-dimathanamine, N,N'-dipropyl-1,10-phenanthroline-2,9-dimathanamine, N,N'-ditert-butyl-1,10-phenanthroline-2,9-dimathanamine, N,N'-dicyclohexyl-1,10-phenanthroline-2,9-dimathanamine) have been synthesized. The ligands and their complexes have been characterized by elemental analysis, IR, and 1H NMR. The complexes have been assayed for antitumor activity in vitro against the mouse leukemia L1210 and the mouse liver carcinoma Bel7402 cell lines. The results showed that the activities of these complexes are significantly dependent on the nature of the alkyl groups on the coordinated amine moieties, and three of these palladium complexes showed lower ID50 values against the two cell lines than cisplatin.
Palladium complexes, N,, N', -dialkyl-1,, 10-phenanthroline-2,, 9-dimathanamine, Cytotoxic activities
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林华宽, Guanghua Zhaoa, Huakoan Lina, *, Ping Yub, Hongwei Suna, Shourong Zhua, Yunti Chena
Chemico-Biological Interactions 116(1998)19-29,-0001,():
-1年11月30日
The DNA binding and interstrand cross-linking properties of the dinuclear platinum complex [{cis-Pt (NH3)2Cl}2bpsu] (NO3)2 (bpsu is 4,4'-dipyridyl sulfide) (II) and the mononuclear complex [cis-Pt (NH3)2Cl (4-methylpyridine)]NO3 (I) were compared with those of [{cis-Pt (NH3)2Cl}2H2N (CH2)4NH2](NO3)2 (III) in order to understand the mode of action of complexes I and II. Both compound I and compound II caused significantly different changes of conformation in poly(dG-dC)•poly(dG-dC) than compound III did. Studies of DNA binding, interstrand cross-linking and fluorescence assay suggest that compound I monofunctionally binds to DNA and compound II bifunctionally binds to DNA, that the dinuclear platinum complex II more efficiently interacts with DNA compared to its monomeric analog, and that platinum I and II complexes both interact with DNA in a non-intercalative mode. All the results indicate that the mode of action of the dinuclear complex II is different from that of the mononuclear complex I.
Conformational changes, DNA-metal complexes, Mononuclear or dinuclear complexes, Platinum complexes
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林华宽, Guanghua Zhaoa, Huakuan Lina, *, Ping Yub, Hongwei Suna, Shourong Zhua, Xuncheng Sua, Yunti Chena
Journal of Inorganic Biochemistry 73(1999)145-149,-0001,():
-1年11月30日
2.320 Å 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) (H20) 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℃, I=0.1mol 1-1 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) C1] NO3 and cis-diamminedichloro- platinum(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.
Mononuclear palladium complexes, Pyridine derivatives, Cytotoxicity
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林华宽, Y. S. ZHANG, Z. M. WANG, H. K. LIN, S. R. ZHU, Y. T. CHEN
,-0001,():
-1年11月30日
The kinetics of acid dissociation of cobalt (II) complexes of novel C-functionalized 13-membered macrocyclic dioxotetraamines was studied using stopped-flow spectrophotometry at different temperatures. The results indicated the dissociation rate follows the law vd 5=CcomkK1K2[H]2/(1+K1[H] 1 K1K2[H]2). On the basis of the experiment facts obtained, the dissociation kinetics is interpreted by a mechanism involving the negatively charged carbonyl oxygen of the complex being rapidly protonated in a pre-rate-determining step, the ratedetermining step being intramolecular hydrogen (enolic tautomer) migration (to imine nitrogen). The dissociation rate reached a plateau in strongly acidic solution. K1 and K2 of the prerate-determining steps and k of the rate-determining step were obtained by means of non-linear least-squares fitting method, and corresponding activation parameters were also obtained by means of temperature coefficient method. The influence of the substituents to the acid dissociation rates has been discussed. The Brönsted type linear-free energy relationship does exist in these C-functionalized dioxotetraamine cobalt (II) complexes. It is first found that the linear relationship between the ∆H≠ and ∆S≠ of the rate-determining step does exist in this and another analogous system.
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林华宽, ZHONG-MING WANG, , ZHI-FEN ZHOU, HUA-KUAN LIN, SHOU-RONG ZHU, YUN-TI CHEN, DONG-QING JIANG, R. KENT MURMANN
,-0001,():
-1年11月30日
The quasi-aromatic metal complex (1,1,2,8,9,9-hexamethyl-4,6-dioxa-5-hydro-3,7,10,14-tetraazacyclotetradecane-2,7,10,12-tetraene)copper (II), [Cu (PnAO)-6H]0 (AH), was synthesized. Reactions of AH were studied spectrophotometrically in acidic media (pH=1~2, EtOH:H2O=1:4 v/v) with para-substituted benzaldehydes (ald). The Cu,2N,3C quasiaromatic heterocyclic ring in AH is highly reactive at the central-aromatic-carbon atom, C12, to most aldehydes. A novel parallel, competitive and consecutive second-order reaction mechanism is proposed. To obtain the rate constants following this mechanism, the Gauss-Newton-Marquardt and Runge-Kutta methods were employed. Consistent results were obtained. Effects of acidity, solvent, temperature and substituent R (R=H, CH3, OCH3, Cl) of the aromatic aldehydes on the reaction rate constants were studied. The results support the proposed SN2 mechanism. A linear free energy relationship between the rate constant k1 and the Hammett parameters for the substituted benzaldehydes as well the activation parameters are presented.
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林华宽, Zhong-Ming Wang, Hua-Kuan Lin, *, Zhi-Fen Zhou, Meng Xu, Tian-Fu Liu, Shou-Rong Zhu and Yun-Ti Chen
Bioorganic & Medicinal Chemistry 9(2001)2849-2855,-0001,():
-1年11月30日
probe, the binding mode of the complexes Cu–L with calf-thymus DNA was studied spectroscopically. The results indicate that the complexes Cu–L perhaps interact with calf-thymus DNA by both intercalative and covalent binding. Kinetics of binding of the cupric complexes to DNA was studied for the first time 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 complexes Cu-L interacting with DNA was observed, and the probable interaction process was discussed in detail. The corresponding kobs and Ea of binding to DNA (where k obs is the observed pseudo-first-order rate constant, E a is the observed energy of activation) were obtained.
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林华宽, Yan-He Guoa, Qing-Chun Gea, Hai Linb, Hua-Kuan Lina, c, *, Shou-Rong Zhua
Polyhedron 21(2002)1005-1015,-0001,():
-1年11月30日
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 p-stacking interactions with the nucleo base 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.
Supramolecular interactions, Tripodal ammonium, Nucleotides, Ternary complexes, Zn (, II),
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林华宽, Zhong-Ming Wang, Hua-Kuan Lin*, Shou-Rong Zhu, Tian-Fu Liu, Yun-Ti Chen
Journal of Inorganic Biochemistry 89(2002)97-106,-0001,():
-1年11月30日
The interaction of the lanthanum (III) La (III)-L (L=N,N'-bis-(1-carboxy-2-methylpropyl)-1,10-phenanthroline-2,9-dimethanamine) complex with calf thymus DNA was studied by electronic spectra, fluorescence spectra and circular dichroic spectra. The La (III)-L complex was assayed for antitumor activity in vitro against the HL-60 (the human leucocytoma) cells, HCT-8 (the human coloadenocarcinoma) cells, BGC-823 (the human carcinoma of stomach) cells, Bel-7402 (the human liver carcinoma) cells and KB (the human nasopharyngeal carcinoma) cells. The results show that the La (III)-L complex has activity against HL-60 cells, Bel-7402 cells and KB cells. Moreover, it is slightly more effective against Bel-7402 cell line than cisplatin. Using ethidium bromide as a fluorescence probe, the binding mode of the La (III)-L complex to calf-thymus DNA was studied spectroscopically. For comparison, the same measurements were carried out with La (III)-Phen [La (III)-1,10-phenanthroline complex] and La (III)-Val [La (III)-L-valine complex]. The results indicate that the La (III)-L and La (III)-Phen complexes possibly interact with calf-thymus DNA by both intercalative and coordination binding, whereas the La (III)-Val complex interacts with calf-thymus DNA by coordination binding. Kinetics of binding of the three complexes to DNA is for the first time studied using ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer under pseudo-first-order condition. The strong two-step mechanisms in the process of the La (III)-L and La (III)-Phen complexes and one step in the process of the complex La (III)-Val interacting with DNA are observed, and the k obs (observed pseudo-first-order rate constant) and E a (observed energy of activation) values of binding to DNA are obtained.
1,, 10-Phenanthroline, L-Valine derivative, Lanthanum (, III), complex, DNA-binding, Thermodynamics, Kinetics, Stopped-flow method, Cytotoxicity, Spectroscopy
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