Synthesis, characterization and crystal structures of the tetrachlorocuprate and tetrabromocadmate salts of the antimalarial mefloquine

Abstract

Two new compounds, bis (DL-erythro-a-2-piperydylium-2,8-bis(trifluoromethyl)-4-quinolinemethanol) tetrachlorocuprate(II) tetrahydrate [LH ? ] 2 [CuCl 4 ] 2-Á4H 2 O 1 [L = mefloquine] and bis(DL-erythro-a-2-piperydylium-2, 8-bis(trifluoromethyl)-4-quinolinemethanol) tetrabromocadmate (II) bis(methanol) [LH ? ] 2 [CdBr 4 ] 2-Á2CH 3 OH 2, have been synthesized and characterized by elemental analysis, 1H-NMR and IR spectroscopy. Single-crystal X-ray diffraction analysis of 1 showed the structure to be ionic with formula unit comprising two protonated monocationic mefloquine molecules of opposite chirality, a tetrachlorocuprate (II) anion and a complement of four water molecules, disordered over several sites. The crystals are orthorhombic, space group Pnma, a = 9.6975(1) Å , b = 29.5385(3) Å , c = 15.9423(1) Å , V = 4566.67(7) Å 3 , Z = 4. The formula unit of compound 2 comprises two protonated monocationic mefloquine molecules, a tetrabromocadmate(II) anion and two molecules of methanol. The crystals are orthorhombic, space group Fdd2, a = 17.2185(5) Å , b = 55.456(2) Å , c = 9.5140(3) Å , V = 9084.6(5) Å 3 , Z = 8. The mefloquine molecule is protonated at the piperidinyl N atom and extensive hydrogen bonding occurs in both crystal structures. The conformation of the mefloquine cation in 1 and 2 is very similar to that recently observed in other salts of the drug, confirming its relevance in the context of antimalarial action.

Crystal structure and Hirshfeld analysis of the kryptoracemate: bis(mefloquinium) chloride p-fluorobenzenesulphonate

“…Data for all known isomeric mefloquine [21,22] and mefloquinium cations [23][24][25][26][27][28][29][30] that have been characterised crystallographically are collected in Table 3. It is remarkable that the 28 characterised mefloquine/mefloquinium species dis-play a high degree of homogeneity in their molecular structures.…”

Synthesis and biological studies of Co(II) and Cd(II) 5-(3,4,5- trimethoxybenzyl) pyrimidine-2,4-diamine (Trimethoprim) complexes

“…Cotrimoxazole (trimethoprim combined with sulphamethoxazole) is used in urinary tract infections (E. coli) respiratory infections (Haemophilies influenzae and pneumococci) and and pneumocystis (Neal, 1993). As a continuation of our work (Obaleye et al, 2007;Obaleye et al, 2008;Obaleye et al, 2009;Tella and Obaleye, 2009;Tella andObaleye, 2010a, 2010b) on metal interactions with chemotherapeutic agents, we investigate the coordination chemistry of 5- (3,4,5-trimethoxybenzyl) pyrimidine-2,4-diamine (Trimethoprim) with Co(II) and Cd(II) metals in an attempt to examine the modes of binding in the solid state and to study biological activity.…”

Metal Complexes as Prospective Antibacterial Agents

“…All the complexes possessed antimalarial activity as confirmed by studies on mice infected with Plasmodium yoelli. Obaleye et al (2009) carried out in vivo antimalarial activities and toxicological studies of some quinoline methanol metal complexes. Antimalarial activities of these complexes were investigated using mice infected with Plasmodium berghei.…”