Monomercaptosuccenic Acid (MMSA).

Monomercaptosuccenic acid; HOOC(H)CH─CH(SH)COOH (MMSA), shown in Figure 1b, is a multidenate chelate with two isolated carboxylic acid groups and one sulfhydryl group (see Table1 for pKa values [1]). It can act as a mono, bi or tridentate ligand using the two oxygens of the carboxylic acid groups as hard binding sites and the sulfur of the sulfhydryl group as a soft binding site. MMSA has acquired less interest in the field of chelation therapy of heavy metals compared to its analogue DMSA where very few reports about MMSA complexation have been cited in the literature [2, 3].Based on potentiometric titration studies MMSA was reported to form 1:1 and 2:1 mole ratios of ligand to metal with Zn(II), Ag(I) and Ni(II) [1].

2-Mercapto-4-Methyl-5-Thiazoleacetic Acid (MCT).

2-mercapto-4-methyl-5-thiazoleacetic acid; C6H7NO2S2(MCT), shown in Figure 1e, is a bidentate chelate, possesses one carboxylic acid, one sulfhydryl and one deprotonated heterocyclic thioamide group (N-C-S)- in which the nitrogen atom is sp2 hybridized. MCT can chelate both hard and soft metal ions where the oxygen atoms of the carboxylic group form the hard binding site for binding hard metal ions and the sulfur of the mercapto group functions as the soft binding site for soft metal ions. Recently, MCT has been utilized in complexation of metal ions like tin(IV) [4, 5]and gold(I) [6] where both carboxylic acid and mercapto groups were found to bind metal ions.

Thiosalicylic acid (TSA).

Thiosalicylic acid; HS(C6H6)CO2H(TSA), shown in Figure 1(c,d) is a bidentate chelate possessing one carboxylic and one sulfhydryl group directly attached to the benzene ring. The carboxylic and sulfhydryl groups can be in ortho, meta and para positions with respect to the aromatic ring (see Table1 for pKa values [7, 8]) . Ortho-TSA has a lower melting point and is more soluble in aqueous solution compared to para-TSA which tends to fit tightly in the crystal lattice due to its higher symmetry. TSA is a versatile ligand, capable of forming complexes with both soft and hard metal centers in either its mono- or doubly deprotonated states, with a variety of bonding modes, including monodentate, chelating and bridging [9]. Recently, TSA has been employed in competing ligand exchange-solid phase extraction studies for the determination of the complexation of dissolved inorganic Hg(II) in natural [10, 11], coastal and estuarine waters [12]. In an interesting study, “Solid Phase Extraction and Determination of Lead in Water Samples Using Silica Gel Homogeneously Modified by Thiosalicylic Acid” TSA was reported to offer a highly selective and stable reagent where the sorption capacity for lead ions is found in the range 64.40-69.90 µmol/g of chelating matrix [13]. In another study, TSA was shown to be efficiently used spectrophotometrically for the determination of copper(II) in aqueous/ethanol solution and synthetic mixtures of non-ferrous alloys containing copper [14].

Compound / pKa1 / pKa2 / pKa3 / pKa4
meso-DMSA / 2.40-2.71 / 3.46-3.48 / 8.89-9.44 / 10.79-11.82
MMSA / 2.53-3.64 / 4.44-4.94 / 9.73-10.64 / ---
o-TSA / 5.72 / 8.88 / --- / ---
p-TSA / 5.8 / --- / --- / ---

Note: pKa1 and pKa2 represent dissociation of COOH groups, while pKa3 and pKa4represent

dissociation of SH groups.

References

1.Lenz, G. R. & Martell, A. E. Metal chelates of mercaptosuccinic and a,a'-dimercaptosuccinic acids. Inorganic Chemistry (Washington, DC, United States) 4, 378-84 (1965).

2.Basinger, M. A., Casas, J. S., Jones, M. M., Weaver, A. D. & Weinstein, N. H. Structural requirements for mercury(II) antidotes. Journal of Inorganic and Nuclear Chemistry 43, 1419-25 (1981).

3.Crisponi, G., Cristiani, F., Nurchi, V. M., Pinna, R. & Estevez, M. J. T. Equilibrium study on Pd(II) chelates of mercapto carboxylic acids. Polyhedron 18, 3257-3262 (1999).

4.Zhang, R., Sun, J. & Ma, C. Synthesis and crystal structure of macrocyclic di-n-butyltin(IV) complex with 2-mercapto-4-methyl-5-thiazoleacetic acid, {[n-Bu2Sn(O2CCH2C4H3NS)SS(C4H3NSCH2CO2)Sn n-Bu2]O}2. Inorganica Chimica Acta 357, 4322-4326 (2004).

5.Ma, C., Sun, J., Qiu, L. & Cui, J. The Synthesis and Characterization of Triorganotin Carboxylates of 2-Mercapto-4-methyl-5-thiazoleacetic Acid: X-ray Crystal Structures of Polymeric Me3Sn[O2CCH2(C4H3NS)S]SnMe3 and Ph3Sn[O2CCH2(C4H3NS)S]SnPh3. Journal of Inorganic and Organometallic Polymers and Materials 15, 341-347 (2005).

6.Tzeng, B.-C., Liu, W.-H., Liao, J.-H., Lee, G.-H. & Peng, S.-M. Self-Assembly of Gold(I) Compounds with (Aza-15-crown-5)dithiocarbamate and 2-Mercapto-4-methyl-5-thiazoleacetic Acid. Crystal Growth & Design 4, 573-577 (2004).

7.Irving, R. J., Nelander, L. & Wadsoe, I. Thermodynamics of the ionization of some thiols in aqueous solution. Acta Chemica Scandinavica 18, 769-87 (1964).

8.Bhattacharyya, U. C. & Lahiri, S. C. Dissociation constant of thiosalicylic acid. Zeitschrift fuer Physikalische Chemie (Muenchen, Germany) 50, 131-4 (1966).

9.Henderson, W. & Nicholson, B. K. Synthesis and X-ray structures of triphenylphosphine-mercury(II) thiosalicylate complexes: novel aggregation processes. Inorganica Chimica Acta 357, 2231-2236 (2004).

10.Black, F. J., Bruland, K. W. & Flegal, A. R. Competing ligand exchange-solid phase extraction method for the determination of the complexation of dissolved inorganic mercury (II) in natural waters. Analytica Chimica Acta 598, 318-333 (2007).

11.Nakayama, H., Hirami, S. & Tsuhako, M. Selective adsorption of mercury ion by mercaptocarboxylic acid intercalated Mg-Al layered double hydroxide. Journal of Colloid and Interface Science 315, 177-183 (2007).

12.Han, S. & Gill, G. A. Determination of Mercury Complexation in Coastal and Estuarine Waters Using Competitive Ligand Exchange Method. Environmental Science and Technology 39, 6607-6615 (2005).

13.Dogan, C. E. & Akcin, G. Solid phase extraction and determination of lead in water samples using silica gel homogeneously modified by thiosalicylic acid. Analytical Letters 40, 2524-2543 (2007).

14.Abu-Bakr, M. S. Complexation equilibria between copper(II) and thiosalicylic acid. Spectrophotometric determination of copper in non-ferrous alloys. Monatshefte fuer Chemie 128, 563-570 (1997).

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