Synthesis, spectroscopic, thermal, antimicrobial and electrochemical characterization of some novel Ru(iii), Pt(iv) and Ir(iii) complexes of pipemidic acid

Abstract

Three new solid complexes of pipemidic acid (Pip-H) with Ru³⁺, Pt⁴⁺ and Ir³⁺ were synthesized and characterized. Pipemidic acid acts as a uni-dentate chelator through the nitrogen atom of the -NH piperazyl ring. The spectroscopic data revealed that the general formulas of Pip-H complexes are [M(L) _n (Cl) _x ]·yH₂O ((1) M = Ru³⁺, L: Pip-H, n = 3, x = 3, y = 6; (2) M = Pt⁴⁺, L: Pip-NH₄, n = 2, x = 4, y = 0 and (3) M = Ir³⁺, L: Pip-H, n = 3, x = 3, y = 6). The number of water molecules with their locations inside or outside the coordination sphere were assigned via thermal analyses (TG, DTG). The DTG curves refer to 2-3 thermal decomposition steps where the first decomposition step at a lower temperature corresponds to the loss of uncoordinated water molecules followed by the decomposition of Pip-H molecules at higher temperatures. Thermodynamic parameters (E*, ΔS*, ΔH* and ΔG*) were calculated from the TG curves using Coats-Redfern and Horowitz-Metzeger non-isothermal models. X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques were carefully used to assign properly the particle sizes of the prepared Pip-H complexes. The biological enhancement of Pip-H complexes rather than free chelate were assessed in vitro against four kinds of bacteria G(+) (Staphylococcus epidermidis and Staphylococcus aureus) and G(-) (Klebsiella and Escherichia coli) as well as against the human breast cancer (MCF-7) tumor cell line.

Fig. 1. Structure and numbering of the pipemidic acid (Pip–H) antibiotic drug.

Fig. 2. (a–d) Chelation modes of quinolone drugs towards metal ions.

Fig. 3. HOMO and LUMO structure of Pip–H free drug.

Fig. 4. Proposed chemical structures of the prepared Ru(iii), Pt(iv) and Ir(iii) Pip–H complexes 1–3.

Fig. 5. ¹H-NMR spectrum of Pt(iv) complex 2.

Fig. 6. TGA and DTG of [Ru(Pip–H)₃(Cl)₃]·6H₂O complex 1.

Fig. 7. X-ray powder diffraction patterns of [M(L)_n(Cl)_x]·yH₂O ((1) M = Ru³⁺, L: Pip–H, n = 3, x = 3, y = 6; (2) M = Pt⁴⁺, L: Pip–NH₄, n = 2, x = 4, y = 0 and (3) M = Ir³⁺, L: Pip–H, n = 3, x = 3, y = 6) complexes 1–3.

Fig. 8. SEM images of [M(L)_n(Cl)_x]·yH₂O ((A) M = Ru³⁺, L: Pip–H, n = 3, x = 3, y = 6; (B) M = Pt⁴⁺, L: Pip–NH₄, n = 2, x = 4, y = 0 and (C) M = Ir³⁺, L: Pip–H, n = 3, x = 3, y = 6) complexes 1–3.

Fig. 9. TEM images of [M(L)_n(Cl)_x]·yH₂O ((A) M = Ru³⁺, L: Pip–H, n = 3, x = 3, y = 6; (B) M = Pt⁴⁺, L: Pip–NH₄, n = 2, x = 4, y = 0 and (C) M = Ir³⁺, L: Pip–H, n = 3, x = 3, y = 6) complexes 1–3.

Fig. 10. CV of (Ir(Pip-H)₃(Cl)3]·6H2O in (Bu)₄N⁺·BF₄⁻–DMSO solution at 100 mV s⁻¹vs. Ag/AgCl, voltage.

Fig. 11. Plot of i_p,cvs. the square root of the scan rate for the (Ir(Pip-H)₃(Cl)₃]·6H₂O complex in (Bu)₄N⁺·BF₄⁻–DMSO solution at the Pt electrode vs. Ag/AgCl reference electrode.

Fig. 12. Plot of current function (i_p,c/ν^1/2) vs. the scan rate of the [Ir(PipH)₃(Cl)₃]·6H₂O complex in (Bu)₄N⁺·BF₄⁻–DMSO at the Pt electrode vs. Ag/AgCl electrode.