Water-Soluble α-Amino Acid Complexes of Molybdenum as Potential Antidotes for Cyanide Poisoning: Synthesis and Catalytic Studies of Threonine, Methionine, Serine, and Leucine Complexes

Abstract

Water-soluble complexes are desirable for the aqueous detoxification of cyanide. Molybdenum complexes with α-amino acid and disulfide ligands with the formula K­[(L)­Mo2O2(μ-S)2(S2)] (L = leu (1), met (2), thr (3), and ser (4)) were synthesized in a reaction of [(DMF)3MoO­(μ-S)2(S2)] with deprotonated α-amino acids; leu, met, thr, and ser are the carboxylate anions of l-leucine, l-methionine, l-threonine, and l-serine, respectively. Potassium salts of α-amino acids (leu (1a), met (2a), thr (3a), and ser (4a)) were prepared as precursors for complexes 1–4, respectively, by employing a nonaqueous synthesis route. The ligand exchange reaction of [Mo2O2(μ-S)2(DMF)6]­(I)2 with deprotonated α-amino acids afforded bis-α-amino acid complexes, [(L)2Mo2O2(μ-S)2] (6–8). A tris-α-amino acid complex, [(leu)2Mo2O2(μ-S)2(μ-leu + H)] (5; leu + H is the carboxylate anion of l-leucine with the amine protonated), formed in the reaction with leucine. 5 crystallized from methanol with a third weakly bonded leucine as a bridging bidentate carboxylate. An adduct of 8 with SCN coordinated, 9, crystallized and was structurally characterized. Complexes 1–4 are air stable and highly water-soluble chiral molecules. Cytotoxicity studies in the A549 cell line gave IC50 values that range from 80 to 400 μM. Cyclic voltammetry traces of 1–8 show solvent-dependent irreversible electrochemical behavior. Complexes 1–4 demonstrated the ability to catalyze the reaction of thiosulfate and cyanide in vitro to exhaustively transform cyanide to thiocyanate in less than 1 h.

Synthesis, Structures, and Solution Studies of a New Class of [Mo2O2S2]-Based Thiosemicarbazone Coordination Complexes

“…Due to its quadrupolar moment, which leads to broad lines, the 14 N nucleus is rarely used in NMR despite a natural abundance of 99.63%. In addition, the 15 N isotope exhibits a spin of 1/2, but the sensitivity of 15 N is much lower than 13 C; the direct 1D NMR measurement is very difficult. HMBC 1 H{ 15 N} experiments were developed in the 1990s, and this method has proved beneficial in determining structures of alkaloids and nitrogen atoms involved in coordination processes and protonation.…”

“…66,67 It allows the acquisition of a 15 N spectrum through the 1 H nuclei linked to nitrogen atoms, and it necessitates about 16 h experiments in 10 mM solution to obtain satisfactory data for our study. HMBC 1 H{ 15 N} experiments not only measure 15 N spectra but also provide the correct assignment of both 15 N and some 1 H peaks. Figure 9 displays the HMBC 1 H{ 15 N} spectra recorded for ligand H 2 L 8 and complex [Mo 2 O 2 S 2 (HL 8 ) 2 ] in DMSO, while those obtained for the other complexes are given in the Supporting Information.…”

“…Figure 9 displays the HMBC 1 H{ 15 N} spectra recorded for ligand H 2 L 8 and complex [Mo 2 O 2 S 2 (HL 8 ) 2 ] in DMSO, while those obtained for the other complexes are given in the Supporting Information. Table 3 lists the 15 N NMR chemical shifts obtained for ligands and the main isomer of complexes. As shown in Figure 9a and the corresponding figures in the SI, the 1 H − 15 N correlations and the strength of the coupling constant in the ligand allow the unambiguous identification of the signals assigned to the nitrogen atoms within the ligands.…”

“…In summary, 15 N NMR data allow the identification of the coordination mode of ligands with the [Mo 2 O 2 S 2 ] 2+ clusters. All of the complexes except for one do not exhibit a coordination of the terminal thioamido group and of the aldehyde/ketone part of the ligand R1.…”

“…These clusters are one of the common forms of Mo­(+V) cations in solution, and many coordination complexes formed with usual ligands were studied as biomimetic models for redox active centers of molybdoenzymes, notably by Schultz and Ott in the 1960s and 1970s. , More recently, complexes combining the [Mo 2 O 2 S 2 ] 2+ core and ligands such as polysulfides, cyclopentadiene, DMF, serine, cysteine, or threonine have been suggested to have biological potential by the group of Suman. Their convenient low cytotoxicity on cells was considered useful for possible therapeutic applications like the development of catalytic drugs, especially for cyanide detoxification, for instance. − Following this work, we recently published a screening study of a series of complexes of [Mo (V) 2 O 2 E 2 ] 2+ (E = O or S) with commercial polycarboxylate ligands demonstrating that the biological properties of such complexes strongly depend on the nature of the ligand. For instance, complexes of EDTA were not active for antioxidative properties, while the complexes synthesized with l -cysteine, l -histidine, and iminodiacetate ligands are highly active .…”