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钌(III)-二甲基亚砜配合物与嘌呤碱衍生物的溶液、固态及生物学特性研究

Solution, solid state and biological characterization of ruthenium(III)-DMSO complexes with purine base derivatives.

作者信息

Turel Iztok, Pecanac Milena, Golobic Amalija, Alessio Enzo, Serli Barbara, Bergamo Alberta, Sava Gianni

机构信息

Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, 1000 Ljubljana, Slovenia.

出版信息

J Inorg Biochem. 2004 Feb;98(2):393-401. doi: 10.1016/j.jinorgbio.2003.12.001.

Abstract

Two new complexes of Ru(III) with purine base derivatives, [mer-RuCl(3)(acv)(DMSO-S)(C(2)H(5)OH)].C(2)H(5)OH (1) (acv=acyclovir, DMSO=dimethyl sulfoxide) and [trans-RuCl(4)(guaH)(DMSO-S)].2H(2)O (2) (guaH=protonated molecule of guanine), were prepared from the same Ru(III) precursor, trans-RuCl(4)(DMSO-S)(2), by substitution of one DMSO-S. Coordination of acv induced also replacement of one chloride by an ethanol molecule. This reactivity difference was explained by striking contrasts in the hydrogen bonding schemes of the two complexes, evidenced in their X-ray crystal structures. In 1 the guanine derivative acyclovir is coordinated to ruthenium through the N(7) atom, while in 2 the protonated guanine molecule is bound through the N(9) atom. Both complexes were also characterized by various physico-chemical methods in the solid state and in the solution. In vitro, the biological activity of 2 and of the previously described complexes [mer-RuCl(3)(acv)(DMSO-S)(CH(3)OH)].0.5CH(3)OH (3) and [mer-RuCl(3)(acv)(DMSO-S)(H(2)O)].H(2)O (4) on tumour cells appear to be very similar to that of NAMI-A (NAMI-A=[ImH][trans-RuCl(4)(DMSO-S)Im]). All compounds are only weakly active on tumour cell proliferation but show an interesting proadhesive effect that suggest possible activity on tumour malignancy.

摘要

两种新的钌(III)与嘌呤碱衍生物的配合物,[mer-RuCl(3)(阿昔洛韦)(二甲亚砜-S)(乙醇)].乙醇 (1)(阿昔洛韦=阿昔洛韦,二甲亚砜=二甲基亚砜)和[trans-RuCl(4)(鸟嘌呤-H)(二甲亚砜-S)].2H(2)O (2)(鸟嘌呤-H=鸟嘌呤的质子化分子),由相同的钌(III)前体trans-RuCl(4)(二甲亚砜-S)(2)通过取代一个二甲亚砜-S制备而成。阿昔洛韦的配位还导致一个氯离子被一个乙醇分子取代。这种反应性差异通过两种配合物氢键模式的显著对比得到解释,这在它们的X射线晶体结构中得到了证明。在1中,鸟嘌呤衍生物阿昔洛韦通过N(7)原子与钌配位,而在2中,质子化的鸟嘌呤分子通过N(9)原子结合。两种配合物还通过各种物理化学方法在固态和溶液中进行了表征。在体外,2以及先前描述的配合物[mer-RuCl(3)(阿昔洛韦)(二甲亚砜-S)(甲醇)].0.5甲醇 (3)和[mer-RuCl(3)(阿昔洛韦)(二甲亚砜-S)(水)].水 (4)对肿瘤细胞的生物活性似乎与NAMI-A(NAMI-A=[ImH][trans-RuCl(4)(二甲亚砜-S)Im])非常相似。所有化合物对肿瘤细胞增殖的活性都很弱,但显示出有趣的促黏附作用,这表明它们可能对肿瘤恶性程度有活性。

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