Stability and binding effects of silver(I) complexes at lipoxygenase-1

Abstract

An anti-inflammatory complex of Ag(I), namely [Ag(tpp)₃(asp)](dmf) [tpp = triphenylphosphine, aspH = aspirin, dmf = N,N-dimethylformamide], was synthesized in an attempt to develop novel metallotherapeutic molecules. STD ¹H NMR experiments were used to examine if this complex binds to LOX-1. The ¹H NMR spectra in buffer Tris/D₂O betrayed the existence of two complexes: the complex of aspirin and the complex of salicylic acid produced after deacetylation of aspirin. Nevertheless, the STD spectra showed that only the complex of salicylic acid is bound to the enzyme. Molecular docking and dynamics were used to complement our study. The complexes were stabilized inside a large LOX-1 cavity by establishing a network of hydrogen bonds and steric interactions. The complex formation with salicylic acid was more favorable. The in silico results provide a plausible explanation of the experimental results, which showed that only the complex with salicylic acid enters the binding cavity.

• Anti-inflammatory activity
• aspirin silver complex
• LOX-1
• molecular docking and dynamics
• STD NMR spectroscopy

Acknowledgements

The authors would like to thank Thomsen R. for providing Molegro software.

Declaration of interest

The authors report no conflicts of interest.

G.L. acknowledges the funding provided by the European Commission for the FP7-REGPOT-2009-1 Project “ARCADE” (Grant Agreement No. 245866) and for the Project “NanoPUZZLES” (Grant Agreement No. NMP-SL-2012-309837). The NMR studies were supported by EN-FIST Center of Excellence (Dunajska 156, SI-1000 Ljubljana, Slovenia) and Ministry of Higher Education, Science and Technology of Slovenia.