Cyanide-Bridged Vitamin B12-Cisplatin Conjugates

• Published in: Chemistry : a European journal 2005-07, Vol.11 (14), p.4089-4095
• Main Authors: Mundwiler, Stefan, Spingler, Bernhard, Kurz, Philipp, Kunze, Susanne, Alberto, Roger
• Format: Article
• Language: English
• Subjects: bioinorganic chemistry; bridging ligands; Cisplatin - chemistry; cobalamins; Cyanides - chemistry; Models, Molecular; Molecular Structure; nucleobases; platinum; Vitamin B 12 - chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200500117

cis‐[PtCl(OH2)(NH3)2]+, the monoactivated form of cisplatin, reacts with the cyano ligand of cobalt in vitamin B12 (cyanocobalamin) to form a CoCNPt conjugate (1). Compound 1 is prepared in good yield directly in aqueous solution. The remaining chloride ligand of PtII 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 B12–nucleobase conjugates. X‐ray structures of the vitamin B12–cisplatin conjugate 1 as well as of the product with coordinated 9‐methylguanine (2) are presented. The coordination geometry at PtII is almost perfectly square‐planar. The structure of the cobalamin compound remains essentially unchanged when compared with the original B12 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. Building bridges! cis‐[PtCl(OH2)(NH3)2]+ coordinates to the cyano ligand of vitamin B12 (cyanocobalamin) to form a CoCNPt‐bridged conjugate (1). The compound is stable in aqueous solution and has been characterized by X‐ray crystallography. The remaining chloride can be exchanged by stronger coordinating ligands such as 2′‐deoxyguanosine to yield B12–nucleoside conjugates.