(105)Rh(III) complexes with acyclic tetrathioether ligands: Potential radiotherapeutic agent

Several Rh(III) complexes with acyclic tetrathioether ligands of the general form (RhCl$sb2$(RCH$sb2$S(CH$sb2)sb{rm n}$S(CH$sb2)sb{rm m}$S(CH$sb2$)nCH$sb2$SR)) X (n = 2 or 3 = m; R = COOH, C$sb6$H$sb5$; X = Cl$sp-$, PF$sb6sp-$, BPh$sb4sp-$) have been synthesized and characterized by spectroscopic (UV-visible, FT-IR, NMR) methods and elemental analyses. The X-ray crystal structures of the dibenzyl substituted tetrathioether Rh(III) complexes allowed full characterization of analogous dicarboxylic acid substituted tetrathioether complexes. Rh$sp{rm III}$ has been found to coordinate to four S atoms (tetradentate) and two chlorine atoms. Different geometrical isomers (e.g., cis-dichloro and trans-dichloro) have been found to form depending on the chain length of the ligand. The ligand with the smaller chain length (e.g., for n,m = 2) cannot afford Rh$sp{rm III}$ to the endo configuration of the four S donor atoms and the formation of the cis-dichloro isomer is favored whereas the larger chain lengths allow Rh$sp{rm III}$ to coordinate to the four S atoms in the endo position to form a trans-dichloro isomers. The solution and the solid state structures have been found to be identical as evidenced by elemental analyses, UV-visible, FT-IR, NMR (1D and 2D) spectroscopy and X-ray diffraction analyses of the complexes. The Rh(III) complex with a macrocyclic tetrathioether ligand 1,5,9,13-Tetrathiacyclohexane-3,11-diol (L8) has been synthesized and characterized and the comparisons of its structural features with the acyclic tetrathioether complexes are described.;The $sp{105}$Rh(III) complexation with the tetrathioether ligands 222-S$sb4$-diAcOH (L1), 232-S$sb4$-diAcOH (L2), and 333-S$sb4$-diAcOH (L3) having the appended -COOH functionalities (R = COOH) was performed and their radioanalytical (chromatographic and electrophoretic) data support that identical complexes were formed as observed at the macroscopic level. The reaction pH, temperature and time were optimized to maximize yields of the complexes. The yield of the complexes varied from 90 to 95% at pH 4-5, and 60 min heating at 80$spcirc$C in an aqueous-ethanol (20% ethanol) medium. Paper electrophoretic analyses indicated that the $sp{105}$Rh(III) complexes carried an overall positive charge at pH 4.5. Chromatographic analyses (counter ion exchange) of the complexes also indicated that the complexes were cationic. The complexes were found to be stable under physioiogical pH for $>$5-6 days. $sp{105}$Rh(III) complexation was also performed with a macrocyclic N$sb3$S$sb2$ ligand, $N,Nsp{prime} $-bis-(2-mercaptoethyl)-1,5-diazacyclooctane-amide (L9) and similar radiochemical results were obtained. Biodistribution studies were performed in mice using the $sp{105}$Rh(III) complexes with two ligands 222-S$sb4$-diAcOH (L1) and 333-S$sb4$-diAcOH (L3) having appended -COOH functionalities and their results are described.