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Arene control over thiolate to sulfinate oxidation in albumin by organometallic ruthenium anticancer complexes

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Hu, Wenbing, Luo, Qun, Ma, Xiaoyan, Wu, Kui, Liu, Jianan, Chen, Yi, Xiong, Shaoxiang, Wang, Jianping, Sadler, P. J. and Wang, Fuyi. (2009) Arene control over thiolate to sulfinate oxidation in albumin by organometallic ruthenium anticancer complexes. Chemistry - A European Journal, Vol.15 (No.27). pp. 6586-6594. ISSN 0947-6539

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Official URL: http://dx.doi.org/10.1002/chem.200900699

Abstract

Interactions of organometallic ruthenium anticancer complexes [Ru(eta(6)-arcne)Cl(en)][PF6] (arene = p-cymene (1) or biphenyl (2), en=ethylenediamine) with human serum albumin were investigated by means of mass spectrometry combined with trypsin digestion, specific sidechain modifications and computational modelling. Both complexes were shown to bind to surface histidine (His128, His247, His510) and methionine (Met298) residues in human albumin, but only the p-cymene complex can gain entry to the crevice containing the free cysteine thiolate (Cys34) and induce oxidation to sulfinate. The two complexes exhibit a similar coordination preference for histidine and methionine residues on the protein surface. His128 binding is favoured both kinetically and thermodynamically. At 310 K, six days of incubation of recombinant human albumin (rHA) with complex I (rHA:Ru 50:250 pm) led to about 18% ruthenation of His128 in the protein. However, the extent of ruthenation of albumin by complex 2 was less than that by I., due to the steric hindrance from the biphenyl ligand. These results imply that the arene ligand in the organometallic ruthenium anticancer complexes plays a crucial role in interactions with proteins.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Q Science > QP Physiology
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Ruthenium, Mass spectrometry, Antineoplastic agents, Bioorganic chemistry, Albumins
Journal or Publication Title: Chemistry - A European Journal
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
ISSN: 0947-6539
Date: 6 July 2009
Volume: Vol.15
Number: No.27
Number of Pages: 9
Page Range: pp. 6586-6594
Identification Number: 10.1002/chem.200900699
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Guo jia zi ran ke xue ji jin wei yuan hui (China) [National Natural Science Foundation (China)] (NSFC), Zhongguo ke xue yuan [Chinese Academy of Sciences], National Basic Research Program of China (973 Program)
Grant number: 20745002 (NSFC), 20773136 (NSFC), 90713020 (NSFC), 2007CB (NSFC), 935601 (NBRPC)
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URI: http://wrap.warwick.ac.uk/id/eprint/27658

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