Journal of Inorganic Biochemistry最新文献

{"title":"Oxaliplatin bioconjugates with human ferritin obtained by protein surface decoration: Characterization and biological evaluation.","authors":"Valentina Vitali, Lara Massai, Andrea Geri, Lucrezia Cosottini, Michele Mannelli, Mirko Severi, Paola Turano, Tania Gamberi, Luigi Messori","doi":"10.1016/j.jinorgbio.2025.113019","DOIUrl":"10.1016/j.jinorgbio.2025.113019","url":null,"abstract":"<p><p>Human H-type ferritin is an attractive protein candidate for the targeted delivery of anticancer metallodrugs. In this study, we report on the formation of ferritin conjugates with oxaliplatin via a direct reaction in solution. This process typically results in the decoration of the protein surface with metallofragments of the type ((R,R)-trans-1,2-diaminocyclohexane)platinum(II) (DACH)Pt. A series of oxaliplatin/ferritin conjugates were obtained and systematically characterized by ESI-MS and ICP measurements. The ESI-MS profiles obtained demonstrate that adduct formation is both time- and concentration-dependent. The nature, stoichiometry and likely anchoring sites of the ferritin-bound platinum fragments were elucidated by ESI-MS analysis coupled with trypsinization experiments. We then evaluated the biological effects of the oxaliplatin-ferritin cage bioconjugate (preprared at 120:1 metal to protein ratio) in comparison to the free drug on A2780 human ovarian cancer cells. We observed that conjugation of oxaliplatin to ferritin resulted in similar platinum uptake by the cells compared to the free drug. However, the anticancer activity of the drug was unexpectedly lost. We critically discuss the implications of these results for the design and preparation of new anticancer platinum-ferritin bioconjugates.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"113019"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review on coordination and biological properties of selenosemicarbazone.","authors":"Vins Daniel, Vipin Singh, Prabal Gupta, Anandaram Sreekanth","doi":"10.1016/j.jinorgbio.2025.113020","DOIUrl":"10.1016/j.jinorgbio.2025.113020","url":null,"abstract":"<p><p>The review highlights the synthesis, coordination behavior, and extensive biological activities of selenosemicarbazones and their metal complexes. Over 110 selenosemicarbazone ligands coordinated with metals such as Cu, Ni, Zn, Pt, and Pd are discussed, showcasing significant structural diversity. These compounds uniquely combine the pharmacophoric semicarbazone moiety with selenium, a redox-active trace element, resulting in enhanced stability, reactivity, and biological performance. Coordinated metal complexes demonstrate potent antibacterial, anticancer, antioxidant, and antiparasitic activities. Mechanistic insights include reactive oxygen species (ROS) generation, metalloenzyme inhibition, and DNA binding. Recent developments in structure-activity relationships and therapeutic targeting are emphasized.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"113020"},"PeriodicalIF":3.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Cu complexes containing methyl-phenanthroline and dipeptides as cytotoxic agents. Synthesis, characterization and in vitro studies","authors":"Lirka Brooks ,&nbsp;Marcos V. Palmeira-Mello ,&nbsp;Carlos Y. Fernandez ,&nbsp;Inés Arandia ,&nbsp;Javier Ellena ,&nbsp;Antonio J. Costa-Filho ,&nbsp;Alzir A. Batista ,&nbsp;Natalia Alvarez ,&nbsp;Gianella Facchin","doi":"10.1016/j.jinorgbio.2025.113089","DOIUrl":"10.1016/j.jinorgbio.2025.113089","url":null,"abstract":"<div><div>The high incidence and mortality associated with cancer evidence the need for novel therapeutic agents. Metal-based coordination compounds offer a diverse arsenal of molecules that can be developed into drugs, beyond those currently in clinical use. Among them, copper complexes are emerging as promising candidates for cancer treatment. In this study, a series of complexes [Cu(L-dipeptide)(met-phen)] (where met-phen: 4-methyl-1,10-phenanthroline and 5-methyl-1,10-phenanthroline) were synthesized and characterized. Solid-state characterization included the determination of the crystal structures of [Cu(Gly-Gly)(4met-phen)]·5.5 H₂O and [Cu(phe-ala)(4met-phen)]·3H₂O. DNA binding was assessed through the intrinsic binding constant (<em>Kb</em>) and relative viscosity measurements, indicating partial intercalation into calf-thymus DNA. The obtained <em>Kb</em> values were approximately tenfold lower than those reported for analogous complexes with phenanthroline. The cytotoxicity of the complexes was evaluated against a panel of human cancer cell lines: metastatic breast adenocarcinoma MDA-MB-231 (triple negative, ATCC: HTB-26), lung epithelial carcinoma A549 (ATCC: CCL-185), ovarian carcinoma A2780 (ECACC 93112519), and nontumoral lung cell line MRC-5 (ATCC: CCL-171). The complexes exhibited potent cytotoxicity, with IC₅₀ values in the low micromolar range, which was significantly more effective than that of cisplatin. [Cu(ala-gly)(5met-phen)] inhibits clonogenic colony formation and induces cellular death above its IC₅₀. These findings evidence that [Cu(L-dipeptide)(met-phen)] complexes are interesting candidates for further <em>in vivo</em> investigation.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113089"},"PeriodicalIF":3.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-photon fluorescence-lifetime imaging of a genetically-encoded heme sensor","authors":"Mae E. James ,&nbsp;Christiane Reick ,&nbsp;Maryam Mohammad Qaed ,&nbsp;Georgia A. Ceeney ,&nbsp;Kornelija Rimgailaite ,&nbsp;Robert G. Blore ,&nbsp;Zofia X. Majewska ,&nbsp;Douha Ghrieb ,&nbsp;Andrea E. Gallio ,&nbsp;Noa A. Marson ,&nbsp;Jaswir Basran ,&nbsp;Ezio Rosato ,&nbsp;Charalambos P. Kyriacou ,&nbsp;Emma L. Raven ,&nbsp;Andrew J. Hudson","doi":"10.1016/j.jinorgbio.2025.113082","DOIUrl":"10.1016/j.jinorgbio.2025.113082","url":null,"abstract":"<div><div>Genetically-encoded fluorescence-based sensors have emerged as an essential tool for measuring the abundance of heme, revealing its trafficking pathways, and probing its signalling and regulatory role in cells. A number of different sensor designs have been described in the literature, and these typically report on the abundance of exchangeable heme <em>via</em> an intensity modulation of the emission from fluorescent-protein reporters. Here, we show that multi-photon fluorescence-lifetime imaging microscopy (MP-FLIM) can be used to monitor the response of heme sensors in transfected-HEK293 cells. The adoption of a multi-photon approach could extend heme quantification further to deep-tissue imaging in the future, where it could also reduce phototoxicity as the non-linear excitation of fluorescent reporters is confined to the focal volume.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113082"},"PeriodicalIF":3.2,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-targeted iridium(III)-PF-06840003 conjugates: Apoptosis induction, IDO inhibition and ICD response","authors":"Chun-Rong Jiang,&nbsp;Yong-Sheng Yang,&nbsp;Lin-Yuan Zhu,&nbsp;Meng-Ting Xu,&nbsp;Rong-Tao Li,&nbsp;Rui-Rong Ye","doi":"10.1016/j.jinorgbio.2025.113086","DOIUrl":"10.1016/j.jinorgbio.2025.113086","url":null,"abstract":"<div><div>Indoleamine 2,3-dioxygenase (IDO) is a potential target for tumor immunotherapy. The growing evidence suggests that IDO inhibitors can exert synergistic effects with chemotherapy drugs. In this study, six complexes, comprising three iridium(III) complexes <strong>Ir-PF-1</strong>–<strong>3</strong> and three ruthenium(II) complexes <strong>Ru-PF-1</strong>–<strong>3</strong>, were synthesized through the coupling of an IDO inhibitor PF-06840003 (PF) with Ir(III) and Ru(II) complexes. Among them, iridium(III) complexes <strong>Ir-PF-1</strong>–<strong>3</strong> exhibited excellent cytotoxicity against various cancer cells, especially HeLa human cervical cancer cells. <strong>Ir-PF-1</strong>–<strong>3</strong> exhibited potent anti-metastatic properties, as evidenced by their ability to inhibit the migration and colony formation of HeLa cells. Furthermore, <strong>Ir-PF-1</strong>–<strong>3</strong> could be hydrolyzed in the cellular environment and released the IDO inhibitory active component PF-06840003, exerting an IDO inhibitory effect. Meanwhile, <strong>Ir-PF-1</strong>–<strong>3</strong> mainly located in mitochondria, where they disrupt mitochondrial structure and function. This is manifested by a decrease in mitochondrial membrane potential (MMP) and an increase in reactive oxygen species (ROS) levels. During apoptosis and immunogenic cell death (ICD) induction, there is also G2/M phase cycle arrest.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113086"},"PeriodicalIF":3.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme and lithospermic acid synergistically inhibit aggregation of human islet amyloid polypeptide: A novel hIAPP inhibitor for the potential therapy of type 2 diabetes","authors":"Bin Xiao,&nbsp;Junhao Xiao,&nbsp;Xiaoying Xiao,&nbsp;Sisi Liu,&nbsp;Hongmei Chen,&nbsp;Shengping Dai,&nbsp;Yan Sui,&nbsp;Huixian Ye","doi":"10.1016/j.jinorgbio.2025.113087","DOIUrl":"10.1016/j.jinorgbio.2025.113087","url":null,"abstract":"<div><div>Amyloid deposition of human islet amyloid polypeptide (hIAPP) is closely linked to the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Developing effective inhibitors to suppress hIAPP aggregation holds significant therapeutic potential for the prevention and treatment of T2DM. Recent researches indicate that both heme and lithospermic acid (LPA) can inhibit hIAPP aggregation. However, heme is prone to induce protein damage under oxidative stress, while LPA exhibits limited inhibitory efficacy despite its antioxidant properties. To overcome these limitations, we aimed to develop a dual-component inhibitor comprising heme and LPA. thioflavin T (ThT) fluorescence, transmission electron microscopy (TEM), circular dichroism (CD) and gel electrophoresis were combined to observe the inhibitory efficacy of heme-LPA co-formulation on hIAPP aggregation. The results demonstrate that LPA and heme can synergistically inhibit hIAPP aggregation. The inhibitory effect of heme-LPA co-formulation on hIAPP aggregation is significantly stronger than that of either component alone. The heme-LPA not only prevents the complete conversion of hIAPP into β-sheet fibrillar structures but also maintains its active monomeric conformation for extended periods. Furthermore, peroxidase activity assays revealed that the presence of LPA significantly reduces the peroxidase activity of heme in a concentration-dependent manner and attenuates peptide nitration damage under H₂O₂-NO₂⁻ oxidative stress. At a heme-to-LPA ratio of 1:4, peptide nitration bands were virtually undetectable. These findings indicate that the dual-component inhibitor heme-LPA represents an efficient and safe strategy for inhibiting hIAPP aggregation. This research provides an important avenue for developing novel anti-hIAPP aggregation inhibitors for the prevention and treatment of T2DM.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113087"},"PeriodicalIF":3.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of ligand topology and iron coordination number on the electronic structure of Fe^III-μ-oxo-Cr^III complexes supported by tetramethylcyclam.","authors":"Ruixi Fan, Jin Xiong, Ang Zhou, Wei-Min Ching, Patrick M Crossland, Barbara Lavina, Michael Y Hu, Jiyong Zhao, Esen E Alp, Lawrence Que, Yisong Guo","doi":"10.1016/j.jinorgbio.2025.113054","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2025.113054","url":null,"abstract":"<p><p>⁵⁷Fe Mössbauer, electron paramagnetic resonance, and ⁵⁷Fe nuclear resonance vibrational spectroscopies are applied to characterize three different Fe^III-O-Cr^III complexes derived from the tetramethylcyclam (TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) ligand. [(CH₃CN)(TMC)Fe^III-O_anti-Cr^III(OTf)₄(NCCH₃)] (1) features an anti configuration where the bridging O-atom is located on the opposite face of all four methyl groups of TMC, which leads to a six-coordinate iron center. Similarly, due to the presence of a pyridine appended to one of the methyl groups of TMC, [(TMC-Py)Fe^III-O_anti-Cr^III(OTf)₄(NCCH₃)] (3) also exhibits an anti configuration with a six-coordinate iron center. But for [(TMC)Fe^III-O_syn-Cr^III(OTf)₄(NCCH₃)] (2), the iron center is five-coordinate due to a syn configuration where the bridging O atom is on the same face of all four methyl groups of TMC. The detailed spectroscopic characterizations reported here reveal that all three complexes exhibit S = 1 spin ground states, which result from antiferromagnetic coupling between an S = 5/2 Fe^III center and an S = 3/2 Cr^III center. However, the detailed magnetic properties derived from Mössbauer and EPR measurements and vibrational properties of these complexes, particularly the symmetric and asymmetric Fe-O-Cr stretching modes, closely reflect the ligand topology difference (anti vs. syn) and the coordination number of the iron center. These spectroscopic properties are used to guide the density functional theory calculations to show how the ligand topology affects the electronic structures of these complexes. Thus, the current study provides a comprehensive geometric and electronic structure correlation of these unique hetero-dinuclear complexes.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"113054"},"PeriodicalIF":3.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fermentative growth decreases the iron demand of Staphylococcus aureus","authors":"Jeffrey M. Boyd ,&nbsp;Gustavo Rios-Delgado ,&nbsp;Karla Esquilín-Lebrón ,&nbsp;Kylie Ryan Kaler ,&nbsp;Gautam Mereddy ,&nbsp;Javiera Norambuena ,&nbsp;Vincent Zheng ,&nbsp;William N. Beavers ,&nbsp;Jisun Kim ,&nbsp;Dane Parker ,&nbsp;Eric P. Skaar ,&nbsp;Ronan K. Carroll ,&nbsp;Jason H. Yang","doi":"10.1016/j.jinorgbio.2025.113085","DOIUrl":"10.1016/j.jinorgbio.2025.113085","url":null,"abstract":"<div><div>Iron (Fe) is an essential nutrient for <em>S. aureus</em> survivability and pathogenesis, but excess Fe can catalyze the formation of toxic oxygen radicals, emphasizing the importance of maintaining proper Fe homeostasis. The essentiality of Fe for bacteria is exploited by host immunity strategies, which employ metal-binding proteins to decrease the availability of metal ions such as Fe. <em>S. aureus</em> responds to Fe limitation using the ferric uptake regulator (Fur) and the Fur protein antagonist (Fpa). During Fe-replete conditions, Fur functions as a transcriptional repressor of target genes. Upon Fe deprivation, Fur repression is relieved with the aid of Fpa, allowing for the increased expression of Fur-regulated genes such as iron uptake systems. We demonstrate that <em>fur</em> inactivation is required during Fe-limited growth and is independent of the described high-affinity Fe uptake systems. Using transcriptomic and metabolomic analyses, we demonstrate that <em>fur</em> inactivation or Fe limitation triggers a decrease in respiration and an increase in fermentation. Triggering fermentative growth allows <em>S. aureus</em> to cope with Fe limitation by having a metabolism less reliant on Fe but allowing for redox balance. Our work provides insight into how <em>S. aureus</em> adapts to iron limitation; a common stress encountered during infection.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113085"},"PeriodicalIF":3.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, spectroscopic, and photophysical studies of Mn(II), Co(II), and Zn(II) complexes with 3-hydroxyflavone: Insights into anticancer activity against prostate cancer cells","authors":"Elżbieta Woźnicka ,&nbsp;Anna Miłoś ,&nbsp;Lidia Zapała ,&nbsp;Małgorzata Kosińska-Pezda ,&nbsp;Ewa Ciszkowicz ,&nbsp;Łukasz Byczyński","doi":"10.1016/j.jinorgbio.2025.113084","DOIUrl":"10.1016/j.jinorgbio.2025.113084","url":null,"abstract":"<div><div>This study reports the synthesis, spectroscopic and photophysical characterization, and anticancer evaluation of Mn(II), Co(II), and Zn(II) complexes with 3-hydroxyflavone. The complexes were obtained in a 1:2 metal-to-ligand molar ratio, yielding solid mononuclear species with the general formula ML₂·nH₂O, where M = Mn(II), Co(II), or Zn(II), and L⁻ = 3-hydroxyflavonate. The compounds were characterized by elemental analysis, thermogravimetric analysis (TG/DTG–DSC), differential scanning calorimetry, UV–Vis, FT-IR, NMR, ¹⁰⁹AgNP LDI MS (Fiber Laser-Generated Silver-109 Nanoparticles for Laser Desorption/Ionization Mass Spectrometry), and fluorescence spectroscopy. Spectroscopic studies indicated coordination through 3-hydroxy and carbonyl groups, leading to structural and electronic modifications of the ligand. Fluorescence properties were strongly influenced by metal coordination, with Zn–3-hydroxyflavone showing the most pronounced emission changes due to altered excited-state intramolecular proton transfer. The cytotoxic activity of the complexes was evaluated against prostate cancer (DU-145), normal prostate (RWPE-2), and normal fibroblast (BJ) cell lines. Zn–3-hydroxyflavone exhibited the highest anticancer activity, with a half-maximal inhibitory concentration (IC₅₀) of 4.08 μM. All complexes displayed selective cytotoxicity, as evidenced by the high viability of normal cell lines even at concentrations exceeding their IC₅₀ values. Recovery assays revealed either a permanent cytotoxic effect or partial regeneration of DU-145 cells following exposure to the complexes. Real-time detection of phosphatidylserine externalization, a key marker of apoptosis, indicated that induction of apoptosis is the most probable mechanism of action for the Mn(II) and Zn(II) complexes against prostate cancer cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113084"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercalative binding, light-switch behavior, and theoretical analysis of Ru(bpy)2dppz-BTDZ]2+: A thiadiazole-extended ruthenium(II) complex","authors":"Mariana O.T. Nogueira ,&nbsp;Pedro Henrique L. da Silva ,&nbsp;Ana Carolina C. do Nascimento ,&nbsp;Nathan B. Soares ,&nbsp;Joyce S.F. Diz ,&nbsp;Steven R. LaPlante ,&nbsp;Luiz Sérgio R. Lamego ,&nbsp;Tanos C.C. França ,&nbsp;Fabio S. Miranda","doi":"10.1016/j.jinorgbio.2025.113083","DOIUrl":"10.1016/j.jinorgbio.2025.113083","url":null,"abstract":"<div><div>The new ruthenium(II) polypyridyl complex [Ru(bpy)₂dppz-BTDZ]²⁺, featuring a thiadiazole-substituted dppz ligand, was synthesized and characterized to investigate its DNA-binding and photophysical properties. Its interaction with calf thymus DNA (Ct-DNA) was studied through UV–visible and emission spectroscopy, competitive binding assays with ethidium bromide (EB), anionic quenching with K₄[Fe(CN)₆], viscosity and molecular modeling. The results indicate that the complex intercalates into DNA, with a binding constant (<em>K</em>_<em>b</em>) of 6.57 ± 0.9 × 10⁶ M⁻¹ and has a 7 % enhancement in the light-switch effect compared to [Ru(bpy)₂dppz]²⁺. DFT calculations characterized the excited states, which were compared to those of [Ru(bpy)₂dppz]²⁺. The presence of the thiadiazole group promotes mixing of MLCT states. Franck–Condon analysis of emission spectra in MeCN, water, and DNA allowed for the estimation of the excited-state free energy. In water, the emissive bright state lies approximately 1300 cm⁻¹ higher than in DNA and approximately 1100 cm⁻¹ higher than in MeCN. This energy trend is consistent with the light-switch behavior observed in this class of complexes. Moreover, the bright-state energies correlated very well with all the observed lifetimes. Docking and molecular dynamics simulations revealed stable intercalative binding in the DNA minor groove, with the Δ-isomer showing enhanced stability.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113083"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}