0cf3beaa739b2b25f1489aafe8da8801 ijms-25-05283.pdf c7f5e1dc13656ff25c14ec31064187a849e50fa5 ijms-25-05283.pdf 57a0fbcb14132a07504c416460551c3ef6fd3f753e5057fbb9b03e5be7c917f0 ijms-25-05283.pdf Title: Experimental and Computational Studies on the Interaction of DNA with Hesperetin Schiff Base CuII Complexes Subject: The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or L1H3), isoniazid (HIN or L2H3), or thiosemicarbazide (HTSC or L3H3) and their CuII complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLnH2(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV–Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants (Kb) of the Cu compounds with CT-DNA, in the range (2.3–9.2) 106, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that – stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LnH2)(AcO)] and [Cu(LnH2)(H2O)]+, the tautomer that binds CuII, amido (am) and not imido (im), and the coordination mode of HTSC (O-, N, S), instead of (O-, N, NH2). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(L1H2am)(AcO)] > [Cu(L2H2am)(AcO)] TO L1H3 > [Cu(L3H2am)(AcO)], in line with the experimental Kb constants, obtained from the UV–Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(L1H2am)(AcO)] is larger than [Cu(L1H2am)(H2O)]+. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules. Keywords: copper complexes; hesperetin Schiff bases; DNA interaction; computational calculations Author: Federico Pisanu, Anna Sykula, Giuseppe Sciortino, Feliu Maseras, Elzbieta Lodyga-Chruscinska and Eugenio Garribba Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon May 13 06:07:21 2024 CEST ModDate: Mon May 13 06:19:52 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4885393 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- AFRYZX+VnURWPalladioL Type 1 Custom yes yes yes 10 0 UWHUDD+EURM10 Type 1 Builtin yes yes yes 16 0 JEJZJP+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 DHAMWO+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 PYQCCE+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 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application/pdf PDFMetadata: Objects: 877 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Experimental Studies Destination: subsection.2.1 Children: Item: Title: Behavior of CuII Complexes in Aqueous Solution Destination: subsubsection.2.1.1 Item: Title: UV Vis Studies on the DNA Binding Destination: subsubsection.2.1.2 Item: Title: Thiazole Orange (TO) Displacement Assay Destination: subsubsection.2.1.3 Item: Title: Computational Studies Destination: subsection.2.2 Children: Item: Title: Geometry Optimization and Speciation Analysis of the Copper Complexes Destination: subsubsection.2.2.1 Item: Title: Docking with DNA Destination: subsubsection.2.2.2 Item: Title: Materials and Methods Destination: section.3 Children: Item: Title: Synthesis Destination: subsection.3.1 Item: Title: Spectroscopic Measurements Destination: subsection.3.2 Item: Title: DFT Calculations Destination: subsection.3.3 Item: Title: Docking Calculations Destination: subsection.3.4 Item: Title: Conclusions Destination: section.4 Item: Title: References Destination: appendix.A. Info: Title: Experimental and Computational Studies on the Interaction of DNA with Hesperetin Schiff Base CuII Complexes Author: Federico Pisanu, Anna Sykula, Giuseppe Sciortino, Feliu Maseras, Elzbieta Lodyga-Chruscinska and Eugenio Garribba Subject: The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or L1H3), isoniazid (HIN or L2H3), or thiosemicarbazide (HTSC or L3H3) and their CuII complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLnH2(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants (Kb) of the Cu compounds with CT-DNA, in the range (2.3 9.2) 106, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that   stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LnH2)(AcO)] and [Cu(LnH2)(H2O)]+, the tautomer that binds CuII, amido (am) and not imido (im), and the coordination mode of HTSC (O-, N, S), instead of (O-, N, NH2). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(L1H2am)(AcO)] > [Cu(L2H2am)(AcO)] TO L1H3 > [Cu(L3H2am)(AcO)], in line with the experimental Kb constants, obtained from the UV Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(L1H2am)(AcO)] is larger than [Cu(L1H2am)(H2O)]+. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules. 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