Journal of Inorganic Biochemistry最新文献_第7页

High oxidizing reactivity of mononuclear nonheme Iron(V)-oxo complexes 单核非血红素铁(V)-氧配合物的高氧化反应性

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-12-03 DOI: 10.1016/j.jinorgbio.2025.113143

Dahyeon Ha , Akhilesh Kumar , Young Hyun Hong , Yong-Min Lee , Shunichi Fukuzumi , Wonwoo Nam

Mononuclear nonheme iron(V)-oxo complexes bearing a tetraamido-macrocyclic (TAML) ligand ([Fe^V(O)(TAML)]⁻) are well characterized and the high oxidizing reactivity has been examined. In contrast, the oxidizing reactivity of mononuclear nonheme iron(V)-oxo complexes with neutral ligands, has yet to be studied because of the extreme short lifetimes of the iron(V)-oxo complexes (ca. several microseconds). We report herein systematic studies on the oxidizing reactivity of formal mononuclear nonheme iron(V)-oxo complexes, [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ [n = 2 where L is neutral ligand or n = 1 where L is monoanion ligand], by using laser-induced transient absorption measurements. The [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ complexes were produced by electron transfer from [Fe^IV(O)(L)]ⁿ⁺ to the triplet excited state of 2,3-dichloro-5,6-dicyano-p-benzoquinone (³DDQ*), which was generated by laser excitation. [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ reacts with H₂O to produce [Fe^III(OOH)(L)]ⁿ⁺, which was further oxidized by DDQ to evolve O₂, accompanied by regeneration of [Fe^II(L)]ⁿ⁺. The decay rates of [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ became faster in the presence of substrates via oxidation of substrates by [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺. Plots of logarithm of the rate constants vs the one-electron oxidation potentials of donor substrates were evaluated in light of the Marcus theory of outer-sphere electron transfer to afford the one-electron reduction potentials and reorganization energies of [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺, which have been compared with those of other iron(V)-oxo complexes. The large reorganization energies of the electron-transfer reduction of the one-electron oxidized species of [Fe^IV(O)(L)]ⁿ⁺ indicate that electron-transfer oxidation of [Fe^IV(O)(L)]ⁿ⁺ occurs at the metal center to produce [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ rather than [Fe^IV(O)(L^•+)]⁽ⁿ⁺¹⁾⁺.

带有四氨基大环（TAML）配体([FeV（O)(TAML)]−）的单核非血红素铁(V)-氧配合物被很好地表征，并检测了其高氧化反应性。相比之下，单核非血红素铁(V)-氧配合物与中性配体的氧化反应性尚未研究，因为铁(V)-氧配合物的寿命极短（约几微秒）。本文采用激光诱导瞬态吸收测量方法，系统研究了形式单核非血红素铁(V)-氧配合物[FeV(O)(L)](n+1)+ [n = 2，其中L为中性配体或n = 1，其中L为单阴离子配体]的氧化反应性。[FeV(O)(L)] n+通过激光激发将电子转移到2,3-二氯-5,6-二氰-对苯醌（3DDQ*）的三态激发态，生成了[FeV(O)(L)](n+1)+配合物。[FeV(O)(L)](n+1)+与H2O反应生成[FeIII(OOH)(L)]n+， DDQ进一步氧化生成O2，并伴有[FeII(L)]n+的再生。通过[FeV(O)(L)](n+1)+对底物的氧化作用，[FeV(O)(L)](n+1)+在底物存在下的衰减速度加快。根据Marcus外球电子转移理论，对给体底物的速率常数与单电子氧化电位的对数图进行了评价，得到了[FeV(O)(L)](n+1)+的单电子还原电位和重组能，并与其他铁(V)-氧配合物进行了比较。单电子氧化态[FeIV(O)(L)]n+的电子转移还原能较大，表明[FeIV(O)(L)]n+的电子转移氧化发生在金属中心生成[FeV(O)(L)](n+1)+，而不是[FeIV(O)(L•+)](n+1)+。

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引用次数: 0

Additional functionality for plecstatin-1-analogous anticancer Ru(η6-p-cymene)Cl complexes plecstatin-1-类似抗癌Ru(6-p-cymene)Cl配合物的附加功能

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-12-01 DOI: 10.1016/j.jinorgbio.2025.113168

Shahid Iqbal , Adnan Ashraf , Anne Dill , Zexiong Lin , Sanam Movassaghi , Muhammad Hanif , Waseeq Ahmad Siddiqui , Stephen M.F. Jamieson , Christian G. Hartinger

The bioactivity of organometallic compounds can be enhanced by modifying the ligand to achieve higher potency or an altered mode of action. Here, we conjugated amino acids to pyridine-2-carbothioamides (PCAs) and formed their Ru^II(cym)Cl (cym = η⁶-p-cymene) organometallics, as confirmed by mass spectrometry, NMR spectroscopy and elemental analysis. The in vitro antiproliferative activities of ligands 1–4 and complexes 1a–4a were established against human non-small cell lung carcinoma (NCI-H460), cervical carcinoma (SiHA), colorectal carcinoma (HCT116) and colon adenocarcinoma (SW480) cell lines. Complexes 1a–3a showed no activity but 4a was moderately potent with an IC₅₀ value of 35 μM in NCI-H460 cells. Organoruthenium compound 4a was also more active than its PCA ligand 4 and the clinically investigated Ru complex KP1339 in NCI-H460 cells.

有机金属化合物的生物活性可以通过修饰配体以获得更高的效力或改变作用方式来增强。通过质谱、核磁共振和元素分析证实，我们将氨基酸偶联到吡啶-2-碳硫酰胺（PCAs）上，形成了RuII(cym)Cl （cym = η - 6-对-cymene）有机金属化合物。配体1-4和配合物1a-4a对人非小细胞肺癌（NCI-H460）、宫颈癌（SiHA）、结直肠癌（HCT116）和结肠腺癌（SW480）细胞系具有体外抗增殖活性。复合物1a-3a在NCI-H460细胞中无活性，而4a具有中等作用，IC50值为35 μM。有机钌化合物4a在NCI-H460细胞中的活性也高于其PCA配体4和临床研究的Ru复合物KP1339。

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引用次数: 0

Oxaliplatin bioconjugates with human ferritin obtained by protein surface decoration: Characterization and biological evaluation. 奥沙利铂与蛋白表面修饰获得的人铁蛋白生物偶联物：表征和生物学评价。

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-12-01 Epub Date: 2025-08-07 DOI: 10.1016/j.jinorgbio.2025.113019

Valentina Vitali, Lara Massai, Andrea Geri, Lucrezia Cosottini, Michele Mannelli, Mirko Severi, Paola Turano, Tania Gamberi, Luigi Messori

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.

人h型铁蛋白是一种有吸引力的靶向递送抗癌金属药物的候选蛋白。在这项研究中，我们报告了通过溶液中的直接反应形成铁蛋白与奥沙利铂的偶联物。这一过程通常会导致蛋白质表面的金属碎片（（R，R)-反式-1,2-二氨基环己烷）铂（II）（DACH）铂）的装饰。获得了一系列奥沙利铂/铁蛋白偶联物，并通过ESI-MS和ICP测量系统地进行了表征。获得的ESI-MS谱图表明，加合物的形成与时间和浓度有关。结合胰蛋白酶化实验，ESI-MS分析了铁蛋白结合铂片段的性质、化学计量和可能的锚定位点。然后，我们评估了奥沙利铂-铁蛋白笼型生物偶联物（金属与蛋白质的比例为120:1）与游离药物对A2780人卵巢癌细胞的生物学效应。我们观察到，与游离药物相比，奥沙利铂与铁蛋白结合导致细胞对铂的吸收相似。然而，这种药物的抗癌活性却出人意料地丧失了。我们批判性地讨论了这些结果对设计和制备新的抗癌铂-铁蛋白生物偶联物的意义。

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引用次数: 0

Targeting non-canonical DNA with π-extended Schiff Base complexes of Zinc(II), Copper(II), and Nickel(II): Insights into G-Quadruplex binding modes 锌（II）、铜（II）和镍（II）的π扩展希夫碱配合物靶向非典型DNA: g -四重体结合模式的研究

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-11-30 DOI: 10.1016/j.jinorgbio.2025.113160

Luisa D'Anna, Silvia Lo Iacono, Laura Marretta, Simona Rubino, Antonio Palumbo Piccionello, Riccardo Bonsignore, Giampaolo Barone

The selective recognition of G-quadruplex (G4) DNA structures by metal complexes holds considerable promise for anticancer drug development, particularly for targeting oncogene promoters and telomeric regions. Herein, we report the synthesis, structural characterization, and DNA-binding strength evaluation of a new series of transition metal complexes derived from a N₄ tetradentate naphthalene-bridged Schiff base ligand (Naphthim). The zinc(II), copper(II) and nickel(II) complexes were obtained via in situ or transmetallation protocols and characterized by NMR, HR-ESI-MS, and elemental analysis. Among them, the copper(II) complex, 2, [CuNaphthim]²⁺, exhibited the highest DNA-binding affinity and G4-stabilizing ability, as assessed by FRET-based DNA melting assays, UV–Vis absorption, and circular dichroism (CD) spectroscopy. Despite lacking cationic side chain substituents, 2 showed moderate stabilization of several G4 structures, with a preferential effect on the cMyc quadruplex. Comparative studies with the benchmark [CuPhenim]²⁺ complex revealed that π-extension of the ligand framework substantially enhances DNA-binding affinity and modulates selectivity.

UV–Vis and CD spectroscopy revealed clear differences in DNA-binding behavior between 2 and [CuPhenim]²⁺, with compound 2 exhibiting stronger and more defined interactions across both G4 and duplex targets. These trends found support by molecular docking, which uncovered distinct binding modes depending on G4 topology and echoed the observed affinity profiles. These findings highlight the Naphthim scaffold as a promising modular platform for the design of G4-targeting metal complexes.

金属配合物对g -四重体（G4） DNA结构的选择性识别为抗癌药物的开发提供了可观的前景，特别是针对癌基因启动子和端粒区域。在此，我们报道了一系列新的过渡金属配合物的合成、结构表征和dna结合强度评价，这些配合物是由N4四齿萘桥接席夫碱配体（Naphthim）衍生的。锌（II）、铜（II）和镍（II）配合物通过原位或金属转化获得，并通过NMR、HR-ESI-MS和元素分析进行了表征。其中，铜（II）配合物2，[CuNaphthim]2+，表现出最高的DNA结合亲和力和g4稳定能力，通过基于fret的DNA熔化试验，紫外-可见吸收和圆二色性（CD）光谱进行了评估。尽管缺乏阳离子侧链取代基，2对几种G4结构表现出适度的稳定，对cMyc四联体有优先作用。与基准的[CuPhenim]2+配合物的比较研究表明，配体框架的π扩展可显著增强dna结合亲和力并调节选择性。紫外-可见光谱和CD光谱显示了2和[CuPhenim]2+之间dna结合行为的明显差异，化合物2在G4和双工靶标上表现出更强、更明确的相互作用。这些趋势得到了分子对接的支持，分子对接揭示了依赖于G4拓扑结构的不同结合模式，并与观察到的亲和谱相呼应。这些发现突出了萘啶支架作为设计g4靶向金属配合物的有前途的模块化平台。

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引用次数: 0

High antioxidant and antibiofilm activity of manganese (II and III) complexes derived from pyridoxal and aromatic hydrazides 吡哆醛和芳酰肼衍生的锰（II和III）配合物具有高抗氧化和抗生物膜活性。

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-11-29 DOI: 10.1016/j.jinorgbio.2025.113166

Josiéli Demetrio Siqueira , Yuri Clemente Andrade Sokolovicz , Morgana Maciél Oliveira , Francisco Mainardi Martins , Marieli Friedrich Loreto , Fallon dos Santos Siqueira , Otávio Augusto Chaves , Marli Matiko Anraku de Campos , Davi Fernando Back

This work presents the synthesis and characterization of seven novel Mn^II/Mn^III-complexes (C1–C7), including one dimeric species, and investigates their potential biological applications. The Mn^II/III complexes were obtained from Schiff base ligands derived from the condensation of pyridoxal hydrochloride with para-substituted aromatic hydrazides. These ligands provided versatile coordination environments, leading to the formation of structurally diverse manganese complexes. All compounds were thoroughly characterized by spectroscopic techniques, elemental analysis, and single-crystal X-ray diffraction for selected examples. In silico calculations were carried out to identify the possible biological activities of the synthetic inorganic compounds, being the antioxidant activity of the Mn^II/III-complexes validated with the nitro blue tetrazolium chloride (NBT) photoreduction assay (superoxide dismutase (SOD)-mimetic behavior). Among the series, complex C6 exhibited the most efficient inhibition of superoxide. Furthermore, the antimicrobial potential of the complexes was thoroughly evaluated through in vitro assays against clinically relevant standard strains commonly used in reference protocols, as well as multidrug-resistant (MDR) clinical isolates (resistant to three or more classes of antimicrobials used in clinical practice), representing medically important pathogens with significant therapeutic challenges. In this case, C6 had excellent antimicrobial activity, highlighting its potential as a multitarget candidate. Overall, these results bring to light the multifunctional potential of Mn^II/Mn^III-complexes based on pyridoxal-derived ligands for biomedical applications.

本文介绍了七种新型MnII/ mniii -配合物（C1-C7）的合成和表征，包括一种二聚体，并探讨了它们的潜在生物学应用。MnII/III配合物是由盐酸吡哆醛与对取代芳酰肼缩合得到的希夫碱配体。这些配体提供了多用途的配位环境，导致结构多样的锰配合物的形成。所有化合物都通过光谱技术、元素分析和选定的单晶x射线衍射进行了彻底的表征。通过硅计算来确定合成的无机化合物可能的生物活性，即MnII/ iii -配合物的抗氧化活性，并通过硝基蓝四氮氯化铵（NBT）光还原试验（超氧化物歧化酶（SOD）模拟行为）进行验证。其中，配合物C6对超氧化物的抑制效果最好。此外，通过对参考方案中常用的临床相关标准菌株以及临床多药耐药（MDR）分离株（对临床实践中使用的三种或更多种抗菌素耐药）的体外试验，对这些复合物的抗菌潜力进行了全面评估，这些菌株代表了具有重大治疗挑战的医学上重要的病原体。在这种情况下，C6具有优异的抗菌活性，突出了其作为多靶点候选药物的潜力。总的来说，这些结果揭示了基于吡哆衍生配体的MnII/ mniii -配合物在生物医学应用中的多功能潜力。

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引用次数: 0

Potent anticancer 5-fluorouracil platinum(IV) prodrugs 强效抗癌5-氟尿嘧啶铂（IV）前药。

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-11-27 DOI: 10.1016/j.jinorgbio.2025.113165

Aleen Khoury , Maria George Elias , Jennette A. Sakoff , Jayne Gilbert , Kieran F. Scott , Janice R. Aldrich-Wright

Six platinum(IV) prodrugs incorporating 5-fluorouracil (5FU) derivatives in the axial positions were synthesised, purified, fully characterised, and their biological activity assessed. The 5FU derivatives, 5FU-acetate and 5FU-methoxybutanoate, were successfully coordinated to [Pt(P_L)(1S,2S-diaminocyclohexane)(OH)₂]²⁺ scaffolds, where P_L = 1,10-phenanthroline (Phen) or 5,6-dimethyl-1,10-phenanthroline (56Me₂Phen). All complexes exhibited exceptional in vitro cytotoxicity across a broad panel of cancer cell lines, with [Pt^IV(56Me₂Phen)(1S,2S-diaminocyclohexane)(5FU-methoxybutanoate)(OH)](NO₃)₂ (6) demonstrating the lowest GI₅₀ of 1 nM against the prostate Du145 cancer cell line. Each complex displayed significantly enhanced activity compared to cisplatin, with 6 being up to 1400-fold more active in selected cancer cell lines. Complexes incorporating the 5FU-methoxybutanoate ligand (5 and 6) were notably more cytotoxic and lipophilic than their 5FU-acetate analogues (1–3), with 6 also exhibiting ∼2-fold greater potency than its platinum(II) precursor. Further studies in the HT29 colon cancer cell line revealed that 5 and 6 induced sustained elevations in reactive oxygen species (ROS) and substantial reductions in mitochondrial membrane potential, indicating that oxidative stress and mitochondrial dysfunction contributed to their cytotoxicity. Collectively, these findings demonstrate that the incorporation of 5FU into platinum(IV) prodrugs enhances both potency and mechanistic activity, with prodrug 6 emerging as a highly promising anticancer candidate.

合成了6种轴位含有5-氟尿嘧啶（5FU）衍生物的铂（IV）前药，对其进行了纯化、完全表征并评估了其生物活性。5FU衍生物5FU-乙酸酯和5FU-甲氧基丁酸酯成功地配位到[Pt(PL)（1S， 2s -二氨基环己烷）（OH） 2]2+支架上，其中PL = 1,10-菲罗啉（Phen）或5,6-二甲基-1,10-菲罗啉（56Me₂Phen）。所有配合物在广泛的癌细胞系中都表现出异常的体外细胞毒性，其中[PtIV(56Me2Phen)（1S， 2s -二氨基环己烷）（5fu -甲氧基丁酸盐）（OH）](NO3)2(6)对前列腺Du145癌细胞系显示出最低的GI₅0为1 nM。与顺铂相比，每种复合物都显示出显著增强的活性，其中6种在选定的癌细胞系中活性高达1400倍。含有5fu -甲氧基丁酸配体（5和6）的配合物明显比它们的5fu -乙酸类似物更具有细胞毒性和亲脂性（1-3），其中6也表现出比其铂（II）前体高2倍的效力。对HT29结肠癌细胞系的进一步研究表明，5和6诱导活性氧（ROS）持续升高，线粒体膜电位大幅降低，表明氧化应激和线粒体功能障碍与它们的细胞毒性有关。总之，这些发现表明5FU与铂（IV）前药的结合增强了效力和机制活性，前药6成为一种非常有前途的抗癌候选药物。

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引用次数: 0

Rare examples of rhenium(I) tricarbonyl iodido complexes with unsymmetrical bipyridines featuring distinguishable rotamers: From synthesis and solid-state/solution-phase isomerism to biological activity 具有可区分旋转体的不对称联吡啶的三羰基碘铼配合物的罕见例子：从合成和固/溶相异构到生物活性。

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-11-27 DOI: 10.1016/j.jinorgbio.2025.113167

Enis Šuta , Adnan Zahirović , Vele Tešević , Sanja Grgurić-Šipka , Sandra Aranđelović , Sead Ljubijankić , Jovana Ljujić , Milica Balaban , Armin Hrnjić , Aleksandar Višnjevac , Nevzeta Ljubijankić

Three novel unsymmetrically substituted 2,2′-bipyridine ligands were prepared by introducing a 2-hydroxyphenyl group at the 6-position and either a 4-methoxyphenyl, 3,4-dimethoxyphenyl or 3,4-methylenedioxyphenyl group at the 4-position, using a modified Kröhnke protocol. Their corresponding rhenium(I) tricarbonyl iodido complexes, fac-[Re(L)(CO)₃I], 1–3, were synthesized and comprehensively characterized by single-crystal X-ray diffraction (SCXRD), ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, ultraviolet–visible (UV–Vis) spectroscopy, cyclic voltammetry (CV), high-resolution mass spectrometry (HRMS), and elemental analysis. The common 6-(2-hydroxyphenyl) moiety predominantly influences the spectroscopic and redox properties of the complexes. SCXRD confirms the facial arrangement of the fac-[Re(CO)₃N₂I] core in all three cases, although solid-state conformational isomerism was observed only in complex 1. In contrast, two NMR-distinguishable isomers are observed in solution for all three complexes. The cytotoxicity of 1–3 was evaluated by MTT assay after 48 h of continuous exposure in several human tumor cell lines (HeLa, PANC-1, MDA-MB-231, A549) and in non-malignant human lung fibroblasts (MRC-5). Notably, all three complexes displayed low-micromolar IC₅₀ values comparable to cisplatin, with the highest activity observed in HeLa cells (5.11–7.45 μM). However, significant activity was also recorded in MRC-5 cells (IC₅₀ = 8.19–8.95 μM), suggesting higher overall toxicity and weaker selectivity compared to cisplatin. Analysis in HeLa cells using bright-field microscopy confirmed a substantial antiproliferative effect.

采用改进的Kröhnke方法，在6位上引入2-羟基苯基，在4位上引入4-甲氧基苯基、3,4-二甲氧基苯基或3,4-亚二氧基苯基，制备了3种新的不对称取代2,2'-联吡啶配体。合成了相应的铼(I)三羰基碘配合物fac-[Re(L)(CO)3I], 1-3，并通过单晶x射线衍射（SCXRD）、1H和13C核磁共振（NMR）光谱、红外（IR）光谱、紫外-可见（UV-Vis）光谱、循环伏安（CV）、高分辨率质谱（HRMS）和元素分析对其进行了综合表征。常见的6-（2-羟基苯基）片段主要影响配合物的光谱和氧化还原性质。SCXRD证实了这三种情况下的face -[Re(CO)3N2I]核的面向排列，尽管只有在配合物1中观察到固态构象异构。相比之下，两个核磁共振可区分异构体在溶液中观察到所有三个配合物。在连续暴露于几种人肿瘤细胞系（HeLa、PANC-1、MDA-MB-231、A549）和非恶性人肺成纤维细胞（MRC-5） 48小时后，用MTT法评估1-3的细胞毒性。值得注意的是，这三种配合物的IC50值与顺铂相当，在HeLa细胞（5.11-7.45 μM）中活性最高。然而，在MRC-5细胞中也记录了显著的活性（IC50 = 8.19-8.95 μM），表明与顺铂相比，总毒性更高，选择性更弱。在HeLa细胞中使用明场显微镜分析证实了其显著的抗增殖作用。

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引用次数: 0

An electrochemical perspective on human sulfite oxidase as a potential nitrite reductase 人亚硫酸盐氧化酶作为潜在亚硝酸盐还原酶的电化学研究。

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-11-26 DOI: 10.1016/j.jinorgbio.2025.113159

Peter D. Giang , Joan Zapiter , Jiayun Zhou , Alexander T. Kaczmarek , Günter Schwarz , Paul V. Bernhardt

The Mo-dependent enzyme human sulfite oxidase (HSO) oxidises highly neurotoxic sulfite to benign sulfate in the final step of cysteine catabolism. Although sulfite is its only known physiological substrate, HSO has been suggested to play a role in the generation of nitric oxide (NO) from nitrite under ischemic conditions. In this work we have investigated the electrochemically driven nitrite reductase activity of HSO mediated by the benzyl viologen radical cation. We show that HSO can act as an effective nitrite reductase with a K_M value of 3.5 mM at pH 7. A heme-free variant of HSO behaves similarly. We also demonstrate electrochemically driven tandem sulfite oxidation and nitrite reduction with HSO using a known Fe^III coordination compound as mediator. Significant pH-dependence of catalytic activity is found.

在半胱氨酸分解代谢的最后一步，钼依赖酶人亚硫酸盐氧化酶（HSO）将高度神经毒性亚硫酸盐氧化为良性硫酸盐。虽然亚硫酸盐是其唯一已知的生理底物，但HSO已被认为在缺血条件下亚硝酸盐生成一氧化氮（NO）中发挥作用。在这项工作中，我们研究了电化学驱动的亚硝酸盐还原酶活性的HSO介导的苯紫根自由基阳离子。结果表明，在pH为7时，HSO可以作为一种有效的亚硝酸盐还原酶，KM值为3.5 mM。HSO的无血红素变体也有类似的行为。我们也证明了电化学驱动串联亚硝酸盐氧化和亚硝酸盐还原与HSO使用已知的FeIII配位化合物作为介质。发现催化活性显著的ph依赖性。

引用次数: 0

A new interpretation for oxygen atom-transfer reactions for the Berg-Holm Oxomolybdenum enzyme model: Evidence for a highly active oxygen atom transfer acceptor Berg-Holm氧钼酶模型对氧原子转移反应的新解释：一个高活性氧原子转移受体的证据。

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-11-25 DOI: 10.1016/j.jinorgbio.2025.113163

Jeremy M. Berg

In 1984, a synthetic model system for certain molybdenum oxotransferase enzymes was reported. These reports claimed that an oxygen atom could be extracted from a designed dioxomolybdenum(VI) complex to produce a monoxomolybdenum(IV) complex without the formation of an oxo-bridged molybdenum(V) binuclear species. The reduced product was shown to accept oxygen atoms from substrates such as dimethylsulfoxide with substrate saturation kinetics. Fifteen years later, it was demonstrated that the reduced product was, in fact, the oxo-bridged molybdenum(V) binuclear species. Here, it is shown that the kinetic data can be reinterpreted in terms of rate-limiting disproportionation of the oxo-bridged molybdenum(V) binuclear species to form a highly reactive monoxomolybdenum(IV) complex. The second order rate constant for oxygen atom transfer from dimethyl sulfoxide to this complex is more than 100,000 times higher than those reported for other monoxomolybdenum(IV) complexes. The five-coordinate molybdenum sites in the dioxomolybdenum(VI) and presumed monoxomolybdenum(IV) complexes are quite similar to those observed for eukaryotic nitrate reductase enzymes and this model system shows relatively rapid reduction of nitrate through a similar mechanistic scheme.

1984年，报道了某些钼氧转移酶的合成模型体系。这些报告声称，可以从设计的二氧钼（VI）配合物中提取一个氧原子，生成单氧钼（IV）配合物，而不会形成氧桥接的钼(V)双核物质。还原产物被证明可以接受来自底物如二甲基亚砜的氧原子，具有底物饱和动力学。15年后，证明了还原产物实际上是氧桥式钼(V)双核物质。本文表明，动力学数据可以用氧桥接钼(V)双核物种的限速歧化来重新解释，以形成高活性的单氧钼（IV）配合物。氧原子从二甲基亚砜转移到该配合物的二级速率常数比其他单钼（IV）配合物高10万倍以上。二氧钼（VI）和假定的单氧钼（IV）配合物中的五坐标钼位点与真核硝酸还原酶中观察到的非常相似，该模型系统通过类似的机制方案显示出相对快速的硝酸还原。

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引用次数: 0

The Neisseria gonorrhoeae cytochrome c2-bacterial peroxidase electron-transfer complex is competent in hydrogen peroxide reduction 淋病奈瑟菌细胞色素c2-细菌过氧化物酶电子转移复合物在过氧化氢还原中是有效的

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-11-25 DOI: 10.1016/j.jinorgbio.2025.113164

Pedro M.S. Bragança , Daniela S. Barreiro , Marta S.P. Carepo , Sofia R. Pauleta

Neisseria gonorrhoeae is a pathogenic bacterium responsible for the disease gonorrhea, which has gained increasing attention in recent years due to the emergence of strains resistant to the currently used antibiotics. In the absence of a vaccine, understanding mechanisms that contribute to infection is imperative. One such mechanism is the reduction of hydrogen peroxide by the outer membrane bound bacterial peroxidase. Here, steady-state kinetics shows that cytochrome c₂, previously implicated in nitrite reduction, is an efficient electron donor to this enzyme, proving to be an alternative to the lipid-modified azurin. The cytochrome c₂-mediated peroxidase activity has a K_M of 0.74 ± 0.08 μM and a k_obs of 18 ± 1 s⁻¹ for hydrogen peroxide, with an optimum pH at 7.7. The pH and ionic-strength dependence of this activity differs from that of azurin, suggesting that the two electron donors can play complementary roles depending on external conditions. Furthermore, the viscosity dependence of the activity suggests that protein-protein interactions are not purely diffusion-controlled but also governed by conformational changes required for complex formation and/or electron transfer, and docking analysis implies that cytochrome c₂ binds near the exposed edge of the electron transferring heme of the bacterial peroxidase.

This study improves our understanding of the periplasmic physiology of N. gonorrhoeae by demonstrating how the pathogen's flexibility in using electron donors enables it to maintain peroxidase activity and cope with oxidative stress in different host environments. These insights could inform future strategies aimed at disrupting redox homeostasis to combat antibiotic-resistant strains.

淋病奈瑟菌是一种导致淋病的致病菌，近年来由于出现了对目前使用的抗生素具有耐药性的菌株，淋病奈瑟菌越来越受到关注。在没有疫苗的情况下，了解导致感染的机制至关重要。其中一种机制是外膜结合细菌过氧化物酶对过氧化氢的还原。这里，稳态动力学表明，细胞色素c2，先前涉及亚硝酸盐还原，是该酶的有效电子供体，证明是脂质修饰的azurin的替代品。过氧化氢介导的细胞色素c2过氧化物酶活性KM为0.74±0.08 μM， kobs为18±1 s−1，最适pH为7.7。该活性对pH值和离子强度的依赖性与azurin不同，这表明两个电子给体可以根据外部条件发挥互补作用。此外，活性的黏度依赖性表明，蛋白质-蛋白质相互作用不是纯粹由扩散控制的，而是由复合体形成和/或电子转移所需的构象变化控制的，对接分析表明，细胞色素c2结合在细菌过氧化物酶的电子转移血红素的暴露边缘附近。本研究通过展示淋病奈瑟菌在使用电子供体方面的灵活性如何使其在不同宿主环境中维持过氧化物酶活性并应对氧化应激，提高了我们对淋病奈瑟菌质周生理学的理解。这些见解可以为未来旨在破坏氧化还原稳态以对抗抗生素耐药菌株的策略提供信息。

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