Thiophene-benzothiazole dyad ligand and its Ag(I) complex – Synthesis, characterization, interactions with DNA and BSA

Authors:

• Martyna Szymańska,
• Małgorzata Insińska-Rak,
• Grzegorz Edward Dutkiewicz,
• Giovanni N. Roviello,
• Marta Fik-Jaskółka,
• Violetta Patroniak

Abstract

The aim of the reported research is to evaluate the significance and potential role of the thiophene moiety in potential DNA and BSA targeting drugs. For this purpose a Thiophene-BenzoThiazole tandem molecule (TBT) and its mononuclear silver(I) complex [Ag(TBT)2]+ was synthesized. The research was carried out using spectroscopic techniques such as circular dichroism (CD), UV–Vis and fluorescence. Based on the presented results the intercalating type of binding to DNA by complex [Ag(TBT)2]+ and ligand TBT was observed. The binding is spontaneous in both cases and the Kb values of both compounds are similar (Kb = 6.40 × 105 and Kb = 5.83 × 105 for ligand TBT and complex [Ag(TBT)2]+, respectively). Yet, this type of interaction was confirmed in ethidium bromide competitive binding experiments and a special emphasis should be put on the higher KSV value for complex [Ag(TBT)2]+ (5.1 × 104) than ligand TBT (3.4 × 104), since it may be the result of the bisintercalation of the complex. It has found confirmation in the increase of the melting temperature (Tm) of DNA treated with complex [Ag(TBT)2]+ of ~5 °C, while in analogues experiment with ligand TBT Tm was only ~1 °C higher. The bisintercalation of the complex is possible since two TBT ligands are bound to the metallic center with planar thiophene moieties placed on the same site. Furthermore, the complex [Ag(TBT)2]+ caused more significant changes in the secondary structures of the model protein BSA than the ligand TBT as determined by CD (reduction of α-helix content by 95 times in presence of the complex vs. stabilization of BSA structure with TBT). It needs to be emphasized, that both compounds bind to BSA via static quenching mechanism, however [Ag(TBT)2]+ has a higher affinity to it than the ligand itself (as evidenced by the extent of hyperchromism). Both compounds interact in hydrophobic site of the protein, however [Ag(TBT)2]+ exhibits higher Stern-Volmer constant KSV = 1.66 × 105 in comparison to TBT KSV = 1.24 × 105. The Scatchard equation allowed one to estimate the compound:BSA binding ratio as 1:1 and 2:3 for ligand and complex, respectively. Moreover, the binding constant Kb is higher for complex (Kb = 4.05 × 107) than ligand (Kb = 3.70 × 105). It confirms that, indeed, both compounds may be distributed by albumins in the body, however the {(BSA)3 - [Ag(TBT)2]+2} adduct is more stable. The synchronous fluorescence spectra indicated that both compounds bind better in Trp than Tyr residues, therefore they may serve as potential molecular targets.