Cob(I)alamin reacts with sucralose to afford an alkylcobalamin: Relevance to in vivo cobalamin and sucralose interaction

Vitamin B-12, viz., cyano- or hydroxo-cobalamin, can be chemically or enzymatically converted into the derivatives methyl- and adenosyl-cobalamin, which are complex organometallic cofactors associated with several cobalamin-dependent enzymes. The reduced form of vitamin B-12, cob(I)alamin (Cbl(I)), obtained by reduction of hydroxocobalamin (OH-Cbl) with e.g. sodium borohydride, is one of the most powerful nucleophiles known. Cbl(I) was shown to react readily with the synthetic sweetener sucralose (1,6-dichloro-1,6-dideoxy-beta-D-fructofuranosyl-4-chloro-4-deoxy-alpha-D-galactopyranoside) in an aqueous system to form an alkylcobalamin (Suc-Cbl). This occurred by replacement of one of the three chlorine atoms of sucralose with a cobalamin moiety. The efficiency of trapping sucralose in presence of excess Cbl(I) was estimated to be > 90%. Furthermore, in an in vitro study using human liver S9 with NADPH regeneration, in presence of OH-Cbl and sucralose, Suc-Cbl was shown to be formed. The Suc-Cbl was characterized primarily by LC-ESI+-MS/MS. Given the human consumption of sucralose from food and beverages, such a reaction between the sweetener and reduced vitamin B-12 could occur in vivo. (C) 2010 Elsevier Ltd. All rights reserved.