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Cyanide‐Bridged Vitamin B 12 –Cisplatin Conjugates
Author(s) -
Mundwiler Stefan,
Spingler Bernhard,
Kurz Philipp,
Kunze Susanne,
Alberto Roger
Publication year - 2005
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200500117
Subject(s) - chemistry , ligand (biochemistry) , moiety , conjugate , stereochemistry , molecule , aqueous solution , medicinal chemistry , hydrogen bond , cyanide , stacking , crystallography , inorganic chemistry , organic chemistry , mathematical analysis , biochemistry , receptor , mathematics
cis ‐[PtCl(OH 2 )(NH 3 ) 2 ] + , the monoactivated form of cisplatin, reacts with the cyano ligand of cobalt in vitamin B 12 (cyanocobalamin) to form a CoCNPt conjugate ( 1 ). Compound 1 is prepared in good yield directly in aqueous solution. The remaining chloride ligand of Pt II is labile. It hydrolyzes slowly in aqueous solution and can be exchanged by stronger coordinating ligands, such as 9‐methylguanine or 2′‐deoxyguanosine, to yield vitamin B 12 –nucleobase conjugates. X‐ray structures of the vitamin B 12 –cisplatin conjugate 1 as well as of the product with coordinated 9‐methylguanine ( 2 ) are presented. The coordination geometry at Pt II is almost perfectly square‐planar. The structure of the cobalamin compound remains essentially unchanged when compared with the original B 12 structure. The guanine moiety of compound 2 binds in a 45° angle to the cisplatin molecule and interacts with neighboring molecules by means of π stacking and hydrogen bonds.