Synthesis and characterization of ethylenediamine derivatized ligands and their platinum complexes

After the serendipitous discovery of Cisplatin, inorganic anticancer drugs have opened up new pathways in the field of metallo pharmaceuticals. Many attempts to overcome the defects of existing drugs are being carried out. In this project three ethylendiamine based platinum(II) complexes were synthesized considering lipophilicity, hydrophilicity and high selectivity towards biological applications. Three novel ethylenediamine sulfonamide ligands; (N(SO₂)(1-piperidine)enH (L1), N(SO₂)(1-naphthalene)enH (L2) and N(SO₂)(2-naphthalene)enH ligand (L3) were synthesized and utilized to synthesize the corresponding platinum(II) complexes; [PtCl₂N(SO₂-1-piperidine)en] (C1), [PtCl₂N(SO₂-1-naphthalene)en] (C2) and [PtCl₂N(SO₂-2-naphthalene)en] (C3) in good yield. The characterization, structure elucidation and physical property measurements were done using spectroscopic methods such as UV-visible, FTIR, proton NMR and fluorescence. The UV-Visible spectra of the complexes possesses absorption peaks in the 200-400 nm region, which arise due to the π→π* and n→π* transitions and show a clear shift from those of the corresponding ligands. The FTIR spectra of the complexes were used to determine the metal-ligand bond formation; the shifts of the S-N bands to higher wave numbers with respect to the S-N band of the ligands depicts the effect of deprotonation of ligand as well as the donation of nitrogen lone pair to platinum in forming the coordination complex. Furthermore, the NH peaks of the metal complexes shift to lower wave numbers compared to the respective ligands proving the formation of coordination complexes via N atoms of the ligands. Fluorescence studies shows that L2, L3, C2 and C3 might have the potential of acting as fluorescence imaging agents with their high fluorescence activity. Literature provides strong evidence that the piperidine moiety is an excellent targeting group for sigma receptors; hence, suggesting a great tendency of L1 and C1 to serve as targeting compounds for sigma receptors. Probable biological targets were foreseen using Swiss TargetPrediction where high probabilities were predicted for carbonic anhydrase II (CA II) and carbonic anhydrase I (CA I) suggesting that further studies are warranted to confirm their biological applicability.