New insights into the chemistry of fac-[Ru(CO)3]2+ fragments in biologically relevant conditions: The CO releasing activity of [Ru(CO)3Cl2(1,3-thiazole)], and the X-ray crystal structure of its adduct with lysozyme

被引：53

作者：

Santos, M. F. A. ^{[2
]}

Seixas, J. D. ^{[1
,3
]}

Coelho, A. C. ^{[1
]}

Mukhopadhyay, A. ^{[2
]}

Reis, P. M. ^{[1
]}

Romao, M. J. ^{[2
]}

Romao, C. C. ^{[1
,3
]}

Santos-Silva, T. ^{[2
]}

机构：

[1] Univ Nova Lisboa, Inst Tecnol Quim & Biol, INRB, P-2780157 Oeiras, Portugal

[2] FCT UNL, Dept Quim, REQUIMTE CQFB, P-2829516 Caparica, Portugal

[3] Alfama Lda, Nucleo Cent 267, P-2740122 Porto Salvo, Portugal

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2012年 / 117卷

关键词：

CORM; Ruthenium complexes; Protein crystallography; CO therapy; CARBON-MONOXIDE; MOLECULE; PROTEINS; COMPLEX; RUTHENIUM(II); DERIVATIVES; REACTIVITY; DESIGN;

D O I：

10.1016/j.jinorgbio.2012.06.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Complexes of the general formula fac-[Ru(CO)(3)L-3](2+), namely CORM-2 and CORM-3, have been successfully used as experimental CO releasing molecules (CO-RMs) but their mechanism of action and delivery of CO remain unclear. The well characterized complex [Ru(CO)(3)Cl-2(1,3-thiazole)] (1) is now studied as a potential model CO-RM of the same family of complexes using LC-MS, FTIR, and UV-vis spectroscopy, together with X-ray crystallography. The chemistry of [Ru(CO)(3)Cl-2(1,3-thiazole)] is very similar to that of CORM-3: it only releases residual amounts of CO to the headspace of a solution in PBS7.4 and produces marginal increase of COHb after long incubation in whole blood. 1 also reacts with lysozyme to form Ru adducts. The crystallographic model of the lysozyme-Ru adducts shows only mono-carbonyl Ru species. [Ru(H2O)(4)(CO)] is found covalently bound to a histidine (His15) and to two aspartates (Asp18 and Asp119) at the protein surface. The CO release silence of both 1 and CORM-3 and their rapid formation of protein-Ru(CO)(x)(H2O)(y) (x = 1,2) adducts, support our hypothesis that fac-[Ru(CO)(3)L-3] CO-RMs deliver CO in vivo through the decay of their adducts with plasma proteins. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：285 / 291

页数：7

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