Phenylethynylcobalamin: A Light‐Stable and Thermolysis‐Resistant Organometallic Vitamin B₁₂ Derivative Prepared by Radical Synthesis

Abstract

Don't take this antivitamin! 2-Phenylethynylcobalamin was prepared in a newly developed radical reaction using cob(II)alamin and 1-iodo-2-phenylethyne. It has an exceptionally short organometallic bond and is a remarkably light-stable and heat-resistant organometallic cobalamin. It is bound well by two important proteins of the human B12 transport system and has properties that are as expected for a new type of an "antivitamin B12 ".

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

“…The derivatives (B 12 -1, B 12 -2 and B 12 -3) were remarkably photostable even after several days of daylight exposure, which is consistent with observations reported for ethynylcobalamin 19 and other acetylide cobalamins. 14,15,20 Plasma stability and transcobalamin binding…”

“…12 Therefore, with this strategy, assessing the efficacy of Cbl to deliver a cytotoxic compound is somewhat biased. However, by applying recent advances in the organometallic chemistry of Cbl described by the groups of Kräutler and Gryko, 14,15 we aim to propose a simple and adjustable structural model to overcome this difficulty and stimulate the design of other motifs. Herein we report the synthesis of new water-soluble vitamin B 12 prodrugs bearing metal complexes at the β-upper side of the cobalt center.…”

Excited electronic states and internal conversion in cyanocobalamin

“…In addition to the native biological function, cobalamin cofactors have recently received increased attention as a vehicle for optically controlled drug delivery and as a source of hydroxyl radicals [11,12] and as antivitamins [13,14]. The effective development of photoactive cobalamin compounds requires a detailed understanding of the intramolecular and intermolecular factors that control their photochemistry and photophysics.…”

Antivitamin B12 Inhibition of the Human B12‐Processing Enzyme CblC: Crystal Structure of an Inactive Ternary Complex with Glutathione as the Cosubstrate

“…[11a] The reaction probably follows a radical process initiated by in-situ generated Cbl II , as proposed for the synthesis 2 . [11a] The UV/Vis-spectrum of 3 (Figure 2) is similar to the one of PhEtyCbl ( 2 ), [11] but differs significantly from the spectra of the organometallic B 12 -cofactors AdoCbl and MeCbl. [13] In neutral aqueous solution, F2PhEtyCbl ( 3 ) exists in the base-on form, and strong acid is needed in order to de-coordinate the 5,6-dimethylbenzimidazole (DMB) base by protonation to 3-H + .…”

“…The crystal structure of 3 showed a base-on Cbl with an ‘upper’ 2,4-difluorophenylethynyl ligand (Figure 2 and SI, Figures S5 and S6 and Table S1). Geometry and bond distances of the inner coordination sphere of the cobalt center of 3 and of PhEtyCbl ( 2 ) [11] are similar. As in 2 [11] and in CNCbl, [14,15] the axial bonds of 3 are short (Co-C1L: 1.877(7) Å, Co-N3N: 2.071(5) Å).…”