# Co(II) Complex of Quercetin-Spectral, Anti-/Pro-Oxidant and Cytotoxic Activity in HaCaT Cell Lines
## 4 Conclusions  
The cobalt(II) complex of quercetin with the formula Co(C\({}_{15}\)H\({}_{9}\)O\({}_{7}\))\({}_{2}\cdot\)2H\({}_{2}\)O was synthetized in its solid state in pH = 7.4. The metal-ligand ratio of 1:2 in the solution was determined using the molar-ratio method. In line with the above-cited reports showing a protective role for quercetin in the amelioration of the oxidative stress-related toxicity of cobalt [34], the presented results indicate that the obtained Co(II)-quercetin complex showed higher antioxidant activity than quercetin alone in the DPPH and FRAP assays. Moreover, the Co(II)-quercetin complex showed slightly lower pro-oxidant activity in the Trolox oxidation assay than the ligand. It should also be noted that the Co(II) complex showed low solubility, suggesting that quercetin may also significantly reduce the concentration of toxic cobalt ions and other transition metals in biological medias. Quercetin was found to be non-toxic towards HaCat keratinocyte cells in the wide concentration range (10-2 577 \(\upmu\)M). The considerably lower obtainable concentrations of the Co(II) complex (0.06-15 \(\upmu\)M) were also found to be non-toxic, with the simultaneous enhancement of antioxidative potential of Co(II)-quercetin complex. The above findings correspond well with the strengthening of the antioxidant defense system observed in CoCl\({}_{2}\)-treated rats upon quercetin and ascorbate administration [34] and contributes to the clarification of the reported protection provided by quercetin against oxidative stress-related and metal-related diseases [47; 48; 49]. Further research on Co(II)-quercetin action in vitro and in vivo models is needed to define the possibility of the application of Co(II)-quercetin and to determine the Q-metal chelation potential in many oxidative stress-related disorders.  
Conceptualization, M.K. ([PERSON]), H.L., M.P.; methodology, M.K. ([PERSON]), H.L., M.P.; formal analysis, M.K. ([PERSON]), H.L., M.P., K.G., E.G., G.S.; investigation, E.G., M.P., H.L., M.K., J.B., M.B.; data curation, M.K. ([PERSON]), E.G., K.G.; writing-original draft preparation, M.K. ([PERSON]), E.G., K.G., H.L., G.S.; writing--review and editing, [PERSON], [PERSON], [PERSON] ([PERSON]), M.P., [PERSON]; visualization, [PERSON] ([PERSON]), [PERSON], H.L.; supervision, [PERSON] ([PERSON]); project administration, [PERSON] ([PERSON]); and funding acquisition, W.L. All authors have read and agreed to the published version of the manuscript.  
Figure 9: Toxicity of quercetin (Q) and its cobalt(II) complex of quercetin (Co-Q) against HaCaT immortalized human keratinocyte cell line, as measured by the fluorimetric neutral red uptake assay. The maximal concentration of Co-Q in the culture media was applied (15 \(\upmu\)M). The concentration range for Co-Q was 0.06–15 \(\upmu\)M, for Q it was 10–2 577 \(\upmu\)M.  
**Funding:** This research was funded by the National Science Centre, Poland, grant no. 2020/39/B/NZ9/01894. [PERSON] acknowledges support from the European Union Horizon 2020 research and innovation programme under grant agreement No 857470 and from European Regional Development Fund via Foundation for Polish Science International Research Agenda PLUS programme grant No MAB PLUS/2018/8.  
**Institutional Review Board Statement:** Not applicable.  
**Informed Consent Statement:** Not applicable.  
**Data Availability Statement:** The data presented in this study are available on request from the corresponding author.  
**Conflicts of Interest:** The authors declare no conflict of interest.