Molecular-modeling design of cadmium-mobilizing agents: a novel biscarbodithioate.

This report describes the design, synthesis, characterization, and in vivo cadmium-mobilizing properties of a novel biscarbodithioate chelating agent, namely, disodium N,N'-diglucosyl-1,9-nonanediamine-N,N'-biscarbodithioate+ ++ (C9G2DTC), HOCH2(CHOH)4CH2(CS2Na)N(CH2)9N(CS2-Na)CH2( CHOH)4CH2OH, which can coordinate to a single cadmium ion with both of its carbodithioate groups (CS2Na) in its folded configuration. When evaluated for its cadmium efficacy at 1.0 mmol/kg x 5 ip in 109Cd-pretreated rats against sodium N-benzyl-D-glucamine-N-carbodithioate (BGDTC) as standard, the biscarbodithioate was found to reduce the whole-body levels of cadmium more rapidly in the rat than BGDTC which contains only one CS2Na group. The whole-body Cd depletions after the first ip injection of the new and the standard compound were 52% and 23%, respectively. The C9G2DTC was found to be more effective in removing cadmium from the liver (% Cd reductions compared to controls: C9G2DTC, 94, and BGDTC, 85), but slightly less effective in reducing renal cadmium levels (% Cd-reductions: C9G2DTC, 44, and BGDTC, 60). The ip LD50 of the bis-DTC was estimated to be slightly in excess of ca. 4.0 mmol/kg in the rat. A molecular model of this chelating agent indicates that, because of the flexibility of the nonane chain, both carbodithioate groups can approach closely enough to each other to permit complexation with the same cadmium ion to give a resulting structure without significant strain. A mechanism for the removal of Cd from CdMT by C9G2DTC is also proposed.