Pyridine-based ligands functionalized with one(PyHis)or two histidine(PydiHis)moieties were synthesized,and their copper_((II))complexes were studied as novel antioxidant systems.The complexes were characterized by pH...Pyridine-based ligands functionalized with one(PyHis)or two histidine(PydiHis)moieties were synthesized,and their copper_((II))complexes were studied as novel antioxidant systems.The complexes were characterized by pH-potentiometric,spectroscopic(UV-vis,circular dichroism,continuous-wave and pulsed electron paramagnetic spectroscopy(EPR)),computational(DFT)and X-ray diffraction methods.The complexes show high thermodynamic stability.The PyHis complex possesses a(COO^(-),N^(py),N^(-),N_(Im))donor set,while PydiHis binds copper_((II))via a(N_(Im),N_(py),N^(-),N_(Im))donor set at physiological pH.The PyHis and PydiHis complexes of copper_((II))exhibit negligible(IC_(50)=147±15μM)and outstanding(IC_(50)=0.64±0.07μM)superoxide dismutase(SOD)activity,respectively.The noted difference is attributed to the structural flexibility of the latter complex as confirmed by pulsed EPR spectroscopy.The antioxidant activity of the copper_((II))complexes was also tested in vivo by monitoring their effects on the mycelial growth of Aspergillus niger under oxidative stress.Both complexes were able to protect the cells under these conditions;however,the copper_((II))complex of PydiHis was more effective in accordance with its excellent SOD activity.Consequently,the copper_((II))complex of PydiHis stands out as an efficient,low-molecularweight SOD mimic combining high catalytic activity with proven biological efficacy under oxidative stress conditions,making it a promising candidate for medical applications.展开更多
基金support of the Hungarian National Research,Development and Innovation Office(OTKA K-139140(I.F.),K-146406(L.K.)and K-138489(E.F.))support of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences and the 2021-4.1.2-NEMZ_KI-2024-00042 project+1 种基金supported by the EKÖP-24-3 University Research Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research,Development and Innovation Fund and the University of Debrecen Scientific Research Bridging Fund(DETKA)Scientific Research Flanders(FWO-Vlaanderen)for infrastructure funding for the EPR instrumentation(No.I004920N).
文摘Pyridine-based ligands functionalized with one(PyHis)or two histidine(PydiHis)moieties were synthesized,and their copper_((II))complexes were studied as novel antioxidant systems.The complexes were characterized by pH-potentiometric,spectroscopic(UV-vis,circular dichroism,continuous-wave and pulsed electron paramagnetic spectroscopy(EPR)),computational(DFT)and X-ray diffraction methods.The complexes show high thermodynamic stability.The PyHis complex possesses a(COO^(-),N^(py),N^(-),N_(Im))donor set,while PydiHis binds copper_((II))via a(N_(Im),N_(py),N^(-),N_(Im))donor set at physiological pH.The PyHis and PydiHis complexes of copper_((II))exhibit negligible(IC_(50)=147±15μM)and outstanding(IC_(50)=0.64±0.07μM)superoxide dismutase(SOD)activity,respectively.The noted difference is attributed to the structural flexibility of the latter complex as confirmed by pulsed EPR spectroscopy.The antioxidant activity of the copper_((II))complexes was also tested in vivo by monitoring their effects on the mycelial growth of Aspergillus niger under oxidative stress.Both complexes were able to protect the cells under these conditions;however,the copper_((II))complex of PydiHis was more effective in accordance with its excellent SOD activity.Consequently,the copper_((II))complex of PydiHis stands out as an efficient,low-molecularweight SOD mimic combining high catalytic activity with proven biological efficacy under oxidative stress conditions,making it a promising candidate for medical applications.
