Cyanide‐Bridged Vitamin B₁₂–Cisplatin Conjugates

Abstract

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[triple chemical bond]N-Pt 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 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 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 degrees angle to the cisplatin molecule and interacts with neighboring molecules by means of pi stacking and hydrogen bonds.

Structures of the b‐ and d‐Acid Derivatives of Vitamin B12 and Their Complexes with [M(CO)3]+ (M = 99mTc, Re)

“…[13,14] We bound several rhenium, technetium and platinum complexes to the cyano group and could confirm the authenticity of the products by X-ray structure analysis. [15,16] The preferred site for derivatisation are the three propionamide and the two acetamide groups bound to the periphery of the corrin ring, which is, like the backloop, bound to three propionamide and two acetamide groups. Scheme 1 gives an overview of the structure of B 12 and the relative positions of the respective groups.…”

Iodination of cisplatin adduct of Vitamin B12 [{B12}-CN-{cis-PtCl(NH3)2}]+

“…Thus, the upper axial position represents a promising site to introduce therapeutic molecules or analytical probes since they are cleaved from the targeting vector B 12 during the conversion processes [13]. [14]. The Pt(II) center can mediate the binding of further pharmacophores or radioactive compounds.…”

Organometallic cobalamin anticancer derivatives for targeted prodrug delivery via transcobalamin-mediated uptake

“…7,10 Nevertheless, metal species such as Pt, Re and Tc complexes could be attached at this position by relying on the ability of Cbl to form heterodinuclear complexes of the general motif {Co-CN-M}. [11][12][13] Although remarkable, these derivatives did not release complexes of identical chemical compositions after reduction of the Co center. 12 Therefore, with this strategy, assessing the efficacy of Cbl to deliver a cytotoxic compound is somewhat biased.…”