JBIC Journal of Biological Inorganic Chemistry最新文献

{"title":"An N-terminal acidic β-sheet domain is responsible for the metal-accumulation properties of amyloid-β protofibrils: a molecular dynamics study","authors":"Carlos Z. Gómez-Castro,&nbsp;Liliana Quintanar,&nbsp;Alberto Vela","doi":"10.1007/s00775-024-02061-1","DOIUrl":"10.1007/s00775-024-02061-1","url":null,"abstract":"<div><p>The influence of metal ions on the structure of amyloid-<span>(beta )</span> (Aβ) protofibril models was studied through molecular dynamics to explore the molecular mechanisms underlying metal-induced Aβ aggregation relevant in Alzheimer’s disease (AD). The models included 36-, 48-, and 188-mers of the Aβ₄₂ sequence and two disease-modifying variants. Primary structural effects were observed at the N-terminal domain, as it became susceptible to the presence of cations. Specially when β-sheets predominate, this motif orients N-terminal acidic residues toward one single face of the β-sheet, resulting in the formation of an acidic region that attracts cations from the media and promotes the folding of the N-terminal region, with implications in amyloid aggregation. The molecular phenotype of the protofibril models based on Aβ variants shows that the AD-causative D7N mutation promotes the formation of N-terminal β-sheets and accumulates more Zn²⁺, in contrast to the non-amyloidogenic rodent sequence that hinders the β-sheets and is more selective for Na⁺ over Zn²⁺ cations. It is proposed that forming an acidic β-sheet domain and accumulating cations is a plausible molecular mechanism connecting the elevated affinity and concentration of metals in Aβ fibrils to their high content of β-sheet structure at the N-terminal sequence.</p><h3>Graphic abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"407 - 425"},"PeriodicalIF":2.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalytic role of histidine-114 in the hydrolytic dehalogenation of chlorothalonil by Pseudomonas sp. CTN-3","authors":"Grayson Gerlich,&nbsp;Callie Miller,&nbsp;Xinhang Yang,&nbsp;Karla Diviesti,&nbsp;Brian Bennett,&nbsp;Judith Klein-Seetharaman,&nbsp;Richard C. Holz","doi":"10.1007/s00775-024-02053-1","DOIUrl":"10.1007/s00775-024-02053-1","url":null,"abstract":"<div><p>Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile; TPN) is an environmentally persistent fungicide that sees heavy use in the USA and is highly toxic to aquatic species and birds, as well as a probable human carcinogen. The chlorothalonil dehalogenase from <i>Pseudomonas</i> sp. CTN-3 (Chd, UniProtKB C9EBR5) degrades TPN to its less toxic 4-OH-TPN analog making it an exciting candidate for the development of a bioremediation process for TPN; however, little is currently known about its catalytic mechanism. Therefore, an active site residue histidine-114 (His114) which forms a hydrogen bond with the Zn(II)-bound water/hydroxide and has been suggested to be the active site acid/base, was substituted by an Ala residue. Surprisingly, Chd^H114A exhibited catalytic activity with a <i>k</i>_<i>cat</i> value of 1.07 s⁻¹, ~ 5% of wild-type (WT) Chd, and a <i>K</i>_<i>M</i> of 32 µM. Thus, His114 is catalytically important but not essential. The electronic and structural aspects of the WT Chd and Chd^H114A active sites were examined using UV–Vis and EPR spectroscopy on the catalytically competent Co(II)-substituted enzyme as well as all-atomistic molecular dynamics (MD) simulations. Combination of these data suggest His114 can quickly and reversibly move nearly 2 Å between one conformation that facilitates catalysis and another that enables product egress and active site recharge. In light of experimental and computational data on Chd^H114A, Asn216 appears to play a role in substrate binding and preorganization of the transition-state while Asp116 likely facilitates the deprotonation of the Zn(II)-bound water in the absence of His114. Based on these data, an updated proposed catalytic mechanism for Chd is presented.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"427 - 439"},"PeriodicalIF":2.7,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron mobilization from intact ferritin: effect of differential redox activity of quinone derivatives with NADH/O2 and in situ-generated ROS","authors":"Narmada Behera,&nbsp;Gargee Bhattacharyya,&nbsp;Satyabrat Behera,&nbsp;Rabindra K. Behera","doi":"10.1007/s00775-024-02058-w","DOIUrl":"10.1007/s00775-024-02058-w","url":null,"abstract":"<div><p>Ferritins are multimeric nanocage proteins that sequester/concentrate excess of free iron and catalytically synthesize a hydrated ferric oxyhydroxide bio-mineral. Besides functioning as the primary intracellular iron storehouses, these supramolecular assemblies also oversee the controlled release of iron to meet physiologic demands. By virtue of the reducing nature of the cytosol, reductive dissolution of ferritin-iron bio-mineral by physiologic reducing agents might be a probable pathway operating in vivo. Herein, to explore this reductive iron-release pathway, a series of quinone analogs differing in size, position/nature of substituents and redox potentials were employed to relay electrons from physiologic reducing agent, NADH, to the ferritin core. Quinones are well known natural electron/proton mediators capable of facilitating both 1/2 electron transfer processes and have been implicated in iron/nutrient acquisition in plants and energy transduction. Our findings on the structure–reactivity of quinone mediators highlight that iron release from ferritin is dictated by electron-relay capability (dependent on E_1/2 values) of quinones, their molecular structure (i.e., the presence of iron-chelation sites and the propensity for H-bonding) and the type/amount of reactive oxygen species (ROS) they generate in situ. Juglone/Plumbagin released maximum iron due to their intermediate E_1/2 values, presence of iron chelation sites, the ability to inhibit in situ generation of H₂O₂ and form intramolecular H-bonding (possibly promotes semiquinone formation). This study may strengthen our understanding of the ferritin-iron-release process and their significance in bioenergetics/O₂-based cellular metabolism/toxicity while providing insights on microbial/plant iron acquisition and the dynamic host–pathogen interactions.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"455 - 475"},"PeriodicalIF":2.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical role of a conserved lysine residue in periplasmic nitrate reductase catalyzed reactions","authors":"Nitai C. Giri,&nbsp;Breeanna Mintmier,&nbsp;Manohar Radhakrishnan,&nbsp;Jonathan W. Mielke,&nbsp;Jarett Wilcoxen,&nbsp;Partha Basu","doi":"10.1007/s00775-024-02057-x","DOIUrl":"10.1007/s00775-024-02057-x","url":null,"abstract":"<div><p>Periplasmic nitrate reductase NapA from <i>Campylobacter jejuni</i> (<i>C. jejuni</i>) contains a molybdenum cofactor (Moco) and a 4Fe–4S cluster and catalyzes the reduction of nitrate to nitrite. The reducing equivalent required for the catalysis is transferred from NapC → NapB → NapA. The electron transfer from NapB to NapA occurs through the 4Fe–4S cluster in NapA. <i>C. jejuni</i> NapA has a conserved lysine (K79) between the Mo-cofactor and the 4Fe–4S cluster. K79 forms H-bonding interactions with the 4Fe–4S cluster and connects the latter with the Moco via an H-bonding network. Thus, it is conceivable that K79 could play an important role in the intramolecular electron transfer and the catalytic activity of NapA. In the present study, we show that the mutation of K79 to Ala leads to an almost complete loss of activity, suggesting its role in catalytic activity. The inhibition of <i>C. jejuni</i> NapA by cyanide, thiocyanate, and azide has also been investigated. The inhibition studies indicate that cyanide inhibits NapA in a non-competitive manner, while thiocyanate and azide inhibit NapA in an uncompetitive manner. Neither inhibition mechanism involves direct binding of the inhibitor to the Mo-center. These results have been discussed in the context of the loss of catalytic activity of NapA K79A variant and a possible anion binding site in NapA has been proposed.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"395 - 405"},"PeriodicalIF":2.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization, and biological activity of cationic ruthenium–arene complexes with sulfur ligands","authors":"Mohammed Zain Aldin,&nbsp;Guillermo Zaragoza,&nbsp;Eva Choquenet,&nbsp;Guillaume Blampain,&nbsp;Gilles Berger,&nbsp;Lionel Delaude","doi":"10.1007/s00775-024-02052-2","DOIUrl":"10.1007/s00775-024-02052-2","url":null,"abstract":"<div><p>Five cationic ruthenium–arene complexes with the generic formula [Ru(SAc)(S₂C·NHC)(<i>p</i>-cymene)](PF₆) (<b>5a–e</b>) were prepared in almost quantitative yields using a straightforward one-pot, two-step experimental procedure starting from [RuCl₂(<i>p</i>-cymene)]₂, an imidazol(in)ium-2-dithiocarboxylate (NHC·CS₂) zwitterion, KSAc, and KPF₆. These half-sandwich compounds were fully characterized by various analytical techniques and the molecular structures of two of them were solved by X-ray diffraction analysis, which revealed the existence of an intramolecular chalcogen bond between the oxygen atom of the thioacetate ligand and a proximal sulfur atom of the dithiocarboxylate unit. DFT calculations showed that the C=S^…O charge transfer amounted to 2.4 kcal mol⁻¹. The dissolution of [Ru(SAc)(S₂C·IMes)(<i>p</i>-cymene)](PF₆) (<b>5a</b>) in moist DMSO-<i>d</i>₆ at room temperature did not cause the dissociation of its sulfur ligands. Instead, <i>p</i>-cymene was slowly released to afford the 12-electron [Ru(SAc)(S₂C·IMes)]⁺ cation that could be detected by mass spectrometry. Monitoring the solvolysis process by ¹H NMR spectroscopy showed that more than 22 days were needed to fully decompose the starting ruthenium–arene complex. Compounds <b>5a–e</b> exhibited a high antiproliferative activity against human glioma Hs683 and human lung carcinoma A549 cancer cells. In particular, the IMes derivative (<b>5a</b>) was the most potent compound of the series, achieving toxicities similar to those displayed by marketed platinum drugs.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"441 - 454"},"PeriodicalIF":2.7,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosynthesized silver nanoparticles prevent bacterial infection in chicken egg model and mitigate biofilm formation on medical catheters","authors":"Lipi Pradhan,&nbsp;Prince Sah,&nbsp;Malay Nayak,&nbsp;Anjali Upadhyay,&nbsp;Pragya Pragya,&nbsp;Shikha Tripathi,&nbsp;Gurmeet Singh,&nbsp;B. Mounika,&nbsp;Pradip Paik,&nbsp;Sudip Mukherjee","doi":"10.1007/s00775-024-02050-4","DOIUrl":"10.1007/s00775-024-02050-4","url":null,"abstract":"<div><p>Investigating the application of innovative antimicrobial surface coatings on medical devices is an important field of research. Many of these coatings have significant drawbacks, including biocompatibility, coating stability and the inability to effectively combat multiple drug-resistant bacteria. In this research, we developed an antibiofilm surface coating for medical catheters using biosynthesized silver nanoparticles (b-Cs-AgNPs) developed using leaves extract of <i>Calliandra surinamensis</i>. Various characterization techniques were employed to thoroughly characterize the synthesized b-Cs-AgNPs and c-AgNPs. b-Cs-AgNPs were compatible with human normal kidney cells and chicken embryos. It did not trigger any skin inflammatory response in in vivo rat model. b-Cs-AgNPs demonstrated potent zone of inhibition of 19.09 mm when subjected to the disc diffusion method in <i>E. coli</i> confirming strong antibacterial property. Different anti-bacterial assays including liquid growth curve, colony counting assay, biofilm formation assay supported the potent antimicrobial efficacy of b-Cs-AgNPs alone and when coated to medical grade catheters. Mechanistic studies reveal the presence of ferulic acid, that was important for the synthesis of b-AgNPs along with enhanced antibacterial effects of b-Cs-AgNPs compared to c-AgNPs, supported by molecular docking analysis. These results together demonstrated the effective role b-Cs-AgNPs in combating infections and mitigating biofilm formations, highlighting their need for further study in the field of biomedical applications.</p><h3>Graphical abstract</h3><p>Schematic Illustration of Eco-Friendly Synthesis for Biofilm Prevention on Medical Catheters and Bacterial Infection Mitigation. Created with BioRender.com.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 3","pages":"353 - 373"},"PeriodicalIF":2.7,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A commentary on studies of brain iron accumulation during ageing","authors":"Mark J. Hackett","doi":"10.1007/s00775-024-02060-2","DOIUrl":"10.1007/s00775-024-02060-2","url":null,"abstract":"<div><p>Brain iron content is widely reported to increase during “ageing”, across multiple species from nematodes, rodents (mice and rats) and humans. Given the redox-active properties of iron, there has been a large research focus on iron-mediated oxidative stress as a contributor to tissue damage during natural ageing, and also as a risk factor for neurodegenerative disease. Surprisingly, however, the majority of published studies have not investigated brain iron homeostasis during the biological time period of senescence, and thus knowledge of how brain homeostasis changes during this critical stage of life largely remains unknown. This commentary examines the literature published on the topic of brain iron homeostasis during ageing, providing a critique on limitations of currently used experimental designs. The commentary also aims to highlight that although much research attention has been given to iron accumulation or iron overload as a pathological feature of ageing, there is evidence to support functional iron deficiency may exist, and this should not be overlooked in studies of ageing or neurodegenerative disease.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"385 - 394"},"PeriodicalIF":2.7,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring of singlet oxygen generation of a novel Schiff-base substituted silicon phthalocyanines by sono-photochemical studies and in vitro activities on prostate cancer cell","authors":"Hiba Messaoudi,&nbsp;Göknur Yaşa Atmaca,&nbsp;Ayşegül Türkkol,&nbsp;Mehmet Dinçer Bilgin,&nbsp;Ali Erdoğmuş","doi":"10.1007/s00775-024-02055-z","DOIUrl":"10.1007/s00775-024-02055-z","url":null,"abstract":"<div><p>This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields (<b>Φ</b>_<b>∆</b>) were determined as 0.43 for <b>Si1a</b>, 0.94 for <b>Q-Si1a</b>, 0.58 for <b>S-Si1a</b>, and 0.49 for <b>B-Sia1</b>. In sono-photochemical studies, the Φ_∆ values were reached to 0.67 for <b>Si1a</b>, 1.06 for <b>Q-Si1a</b>, 0.65 for <b>S-Si1a</b>, and 0.67 for <b>B-Sia1</b>. In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 3","pages":"303 - 314"},"PeriodicalIF":2.7,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectroscopic, electrochemical, and kinetic trends in Fe(III)–thiolate disproportionation near physiologic pH","authors":"Levi A. Ekanger,&nbsp;Ruhi K. Shah,&nbsp;Matthew E. Porowski,&nbsp;Zach Ziolkowski,&nbsp;Alana Calello","doi":"10.1007/s00775-024-02051-3","DOIUrl":"10.1007/s00775-024-02051-3","url":null,"abstract":"<div><p>In addition to its primary oxygen-atom-transfer function, cysteamine dioxygenase (ADO) exhibits a relatively understudied anaerobic disproportionation reaction (ADO-Fe(III)-SR → ADO-Fe(II) + ½ RSSR) with its native substrates. Inspired by ADO disproportionation reactivity, we employ [Fe(tacn)Cl₃] (tacn = 1,4,7-triazacyclononane) as a precursor for generating Fe(III)–thiolate model complexes in buffered aqueous media. A series of Fe(III)–thiolate model complexes are generated in situ using aqueous [Fe(tacn)Cl₃] and thiol-containing ligands cysteamine, penicillamine, mercaptopropionate, cysteine, cysteine methyl ester, <i>N</i>-acetylcysteine, and <i>N</i>-acetylcysteine methyl ester. We observe trends in UV–Vis and electron paramagnetic resonance (EPR) spectra, disproportionation rate constants, and cathodic peak potentials as a function of thiol ligand. These trends will be useful in rationalizing substrate-dependent Fe(III)–thiolate disproportionation reactions in metalloenzymes.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 3","pages":"291 - 301"},"PeriodicalIF":2.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid","authors":"Shanjia Li,&nbsp;Xupeng Zhang,&nbsp;Tiankun Zhao,&nbsp;Nan Liu,&nbsp;Yong Zhang,&nbsp;Peng Wang,&nbsp;Zhongduo Yang,&nbsp;Thomas Huhn","doi":"10.1007/s00775-024-02059-9","DOIUrl":"10.1007/s00775-024-02059-9","url":null,"abstract":"<div><p>Eighteen novel Ti(IV) complexes stabilized by different chelating amino-<i>bis</i>(phenolato) (ONNO, ONON, ONOO) ligands and 2,6-dipicolinic acid as a second chelator were synthesized with isolated yields ranging from 79 to 93%. Complexes were characterized by ¹H and ¹³C-NMR spectroscopy, as well as by HRMS and X-Ray diffraction analysis. The good to excellent aqueous stability of these Ti(IV) complexes can be modulated by the substitutions on the 2-position of the phenolato ligands. Most of the synthesized Ti(IV) complexes demonstrated potent inhibitory activity against Hela S3 and Hep G2 tumor cells. Among them, the naphthalenyl based Salan type <b>2j</b>, 2-picolylamine based [ONON] type <b>2n</b> and <i>N</i>-(2-hydroxyethyl) based [ONOO] type <b>2p</b> demonstrated up to 40 folds enhanced cytotoxicity compared to cisplatin together with a significantly reduced activity against healthy AML12 cells. The three Ti(IV) complexes exhibited fast cellular uptake by Hela S3 cells and induced almost exclusively apoptosis. <b>2j</b> could trigger higher level of ROS generation than <b>2p</b> and <b>2n</b>.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 3","pages":"315 - 330"},"PeriodicalIF":2.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}