A study of the synthesis, characterization and cytotoxicity of tropones and troponimines and its Rhenium(I) coordination compounds

Abstract

Rhenium(I) tricarbonyl complexes have gained much interest over the past years for its possible applications in radiopharmacy, chemotherapy and photodynamic therapy (PDT). In order to defeat cancer worldwide, it is imperative that scientists develop better, and improve current treatment methods. In this study the aim is to expand the knowledge on Re(I) tricarbonyl complexes and its potential in anticancer research, with the focus on good cytotoxicity and photoluminescent properties. Five N,O bidentate 2-(alkylamino)tropone ligand systems were successfully synthesized in yields between 22 % and 66 %. Nine N,N’ bidentate aminotroponimine ligand systems were successfully synthesized in yields ranging from 22 % to 74 %. Five Re(I) tricarbonyl complexes of the type fac-[Re(CO)3(H2O)(N,O)] (N,O = different N,O bidentate ligands) and nine of the type fac-[Re(CO)3(H2O)(N,N’)] (N,N’ = different N,N’ bidentate ligands) were synthesized successfully in yields of 66 % - 75 % and 53 % - 94 %, respectively. The crystal structures of 2-tosyloxytropone (TropOTs), 2-(methylamino)tropone (TropNHMe) and 2-(2-fluoroethylamino)tropone (TropNHEtF) were obtained, solved and reported in this study. The structures of these molecules have interesting packing patterns in their unit cells. TropNHMe has three molecules in the asymmetric unit and TropOTs and TropNHEtF have only one. Hydrogen bonding interactions are observed in all three the structures and in TropNHMe these interactions form one-dimensional infinite chains. In the structures of TropOTs and TropNHMe π-π interactions are observed, but not in TropNHEtF, where hydrogen bonding interactions are possibly responsible for the packing pattern observed in the unit cell. The in vitro cytotoxicity of all the ligands and four of the fac-[Re(CO)3(H2O)(N,O)] (N,O = different N,O bidentate ligands) complexes was determined. The results include IC50 values ranging from 0.45 μM - 36.1 μM for the ligands and 47.0 μM - 77.4 μM for the complexes. Four of the N,N’ bidentate ligands, namely [(EtPh,Bn)ATI]H, [(Me,Bn)ATI]H, [(Et,Bn)ATI]H and [(EtPh)2ATI]H have IC50 values of 0.45, 0.66, 1.10 and 2.4 μM, respectively, which are lower than that of cisplatin, the control in this study, with an IC50 value of 3.26 μM. Selected ligands and complexes were evaluated for its photoluminescent properties and the results are reported in this study. The excitation wavelengths of the ligands and complexes range from 257 nm - 377 nm and the emission wavelengths from 405 nm - 517 nm. The intensity of the emissions ranges from 2.37 x 103 to 21.5 x 103 arbitrary units with [(Me)2ATI]H having an exceptionally high intensity value of 218.0 x 103 arbitrary units. The 2-(alkylamino)tropone ligands and its complexes have longer excitation wavelengths than that of the aminotroponimine ligands and its complexes with fac-[Re(CO)3(H2O)(TropNEtPh)] being the exception. TropNHEtF, TropNHBn and TropNHEtPh and their Re(I) tricarbonyl complexes fac-[Re(CO)3(H2O)(TropNEtF)], fac-[Re(CO)3(H2O)(TropNBn)] and fac-[Re(CO)3(H2O)(TropNEtPh)] are the three ligand-complex pairs that exhibit red shifts in their emissions from the ligand to the complex. The quantum yields of the compounds could unfortunately not be determined successfully due to the low intensities of the emissions.