Journal of Biological Inorganic Chemistry最新文献_第9页

Fractionation of selenium isotopes during biofortification of Saccharomyces cerevisiae and the influence of metabolic labeling with 15N 酿酒酵母生物强化过程中硒同位素的分离及15N代谢标记的影响

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-08-30 DOI: 10.1007/s00775-023-02016-y

Luis Fernando Mejia Diaz, Jakub Karasinski, Kazimierz Wrobel, Alma Rosa Corrales Escobosa, Eunice Yanez Barrientos, Ludwik Halicz, Ewa Bulska, Katarzyna Wrobel

Isotope fractionation of metals/metalloids in biological systems is an emerging research area that demands the application of state-of-the-art analytical chemistry tools and provides data of relevance to life sciences. In this work, Se uptake and Se isotope fractionation were measured during the biofortification of baker’s yeast (Saccharomyces cerevisiae)—a product widely used in dietary Se supplementation and in cancer prevention. On the other hand, metabolic labeling with ¹⁵N is a valuable tool in mass spectrometry-based comparative proteomics. For Se-yeast, such labeling would facilitate the assessment of Se impact on yeast proteome; however, the question arises whether the presence of ¹⁵N in the microorganisms affects Se uptake and its isotope fractionation. To address the above-mentioned aspects, extracellularly reduced and cell-incorporated Se fractions were analyzed by hydride generation–multi-collector inductively coupled plasma–mass spectrometry (HG MC ICP–MS). It was found that extracellularly reduced Se was enriched in light isotopes; for cell-incorporated Se, the change was even more pronounced, which provides new evidence of mass fractionation during biological selenite reduction. In the presence of ¹⁵N, a weaker preference for light isotopes was observed in both, extracellular and cell-incorporated Se. Furthermore, a significant increase in Se uptake for ¹⁵N compared to ¹⁴N biomass was found, with good agreement between hydride generation microwave plasma–atomic emission spectrometry (HG MP–AES) and quadrupole ICP–MS results. Biological effects observed for heavy nitrogen suggest ¹⁵N-driven alteration at the proteome level, which facilitated Se access to cells with decreased preference for light isotopes.

Graphical abstract

生物系统中金属/准金属的同位素分馏是一个新兴的研究领域，需要应用最先进的分析化学工具，并提供与生命科学相关的数据。在这项工作中，在面包酵母（酿酒酵母）的生物强化过程中测量了硒的摄取和硒同位素分馏，面包酵母是一种广泛用于膳食硒补充和癌症预防的产品。另一方面，15N代谢标记在基于质谱的比较蛋白质组学中是一种有价值的工具。对于硒酵母，这种标记将有助于评估硒对酵母蛋白质组的影响；然而，产生的问题是微生物中15N的存在是否影响硒的吸收及其同位素分馏。为了解决上述方面，通过氢化物发生-多收集器电感耦合等离子体质谱法（HG-MC-ICP–MS）分析细胞外还原和细胞掺入的Se组分。研究发现，细胞外还原硒富含轻同位素；对于细胞掺入的Se，这种变化甚至更为明显，这为生物亚硒酸盐还原过程中的质量分馏提供了新的证据。在15N存在的情况下，细胞外和细胞内硒对轻同位素的偏好较弱。此外，与14N生物量相比，15N的硒摄取量显著增加，氢化物发生微波等离子体原子发射光谱法（HG MP–AES）和四极ICP–MS结果之间具有良好的一致性。对重氮观察到的生物学效应表明，15N在蛋白质组水平上驱动了改变，这促进了硒进入对轻同位素偏好降低的细胞。图形摘要

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引用次数: 0

The mechanism of antiproliferative activity of the oxaliplatin pyrophosphate derivative involves its binding to nuclear DNA in cancer cells 奥沙利铂焦磷酸衍生物的抗增殖活性机制涉及其与癌症细胞核DNA的结合

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-08-25 DOI: 10.1007/s00775-023-02017-x

Jitka Prachařová, Hana Kostrhunová, Alessandra Barbanente, Nicola Margiotta, Viktor Brabec

(1R,2R-diaminocyclohexane)(dihydropyrophosphato) platinum(II), also abbreviated as RRD2, belongs to a class of potent antitumor platinum cytostatics called phosphaplatins. Curiously, several published studies have suggested significant mechanistic differences between phosphaplatins and conventional platinum antitumor drugs. Controversial findings have been published regarding the role of RRD2 binding to DNA in the mechanism of its antiproliferative activity in cancer cells. This prompted us to perform detailed studies to confirm or rule out the role of RRD2 binding to DNA in its antiproliferative effect in cancer cells. Here, we show that RRD2 exhibits excellent antiproliferative activity in various cancer cell lines, with IC₅₀ values in the low micromolar or submicromolar range. Moreover, the results of this study demonstrate that DNA lesions caused by RRD2 contribute to killing cancer cells treated with this phosphaplatin derivative. Additionally, our data indicate that RRD2 accumulates in cancer cells but to a lesser extent than cisplatin. On the other hand, the efficiency of cisplatin and RRD2, after they accumulate in cancer cells, in binding to nuclear DNA is similar. Our results also show that RRD2 in the medium, in which the cells were cultured before RRD2 accumulated inside the cells, remained intact. This result is consistent with the view that RRD2 is activated by releasing free pyrophosphate only in the environment of cancer cells, thereby allowing RRD2 to bind to nuclear DNA.

Graphical abstract

（1R，2R二氨基环己烷）（二氢焦磷酸）铂（II），也称为RRD2，属于一类强效抗肿瘤铂细胞抑制剂，称为磷酸铂。奇怪的是，几项已发表的研究表明，磷酸铂和传统铂类抗肿瘤药物之间存在显著的机制差异。关于RRD2与DNA结合在其在癌症细胞中抗增殖活性机制中的作用，已经发表了有争议的研究结果。这促使我们进行详细的研究，以确认或排除RRD2与DNA结合在其抗癌症细胞增殖作用中的作用。在此，我们发现RRD2在各种癌症细胞系中表现出优异的抗增殖活性，IC50值在低微摩尔或亚摩尔范围内。此外，本研究的结果表明，RRD2引起的DNA损伤有助于杀死用这种磷铂衍生物治疗的癌症细胞。此外，我们的数据表明，RRD2在癌症细胞中积累，但其程度低于顺铂。另一方面，顺铂和RRD2在癌症细胞中积累后与核DNA结合的效率相似。我们的结果还表明，在细胞内积累RRD2之前培养细胞的培养基中的RRD2保持完整。这一结果与RRD2仅在癌症细胞的环境中通过释放游离焦磷酸盐而被激活的观点一致，从而使RRD2与核DNA结合。图形摘要

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引用次数: 0

Sulfur-bridging the gap: investigating the electrochemistry of novel copper chelating agents for Alzheimer's disease applications 硫桥接间隙：研究新型铜螯合剂在阿尔茨海默病中的电化学应用

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-08-18 DOI: 10.1007/s00775-023-02013-1

Emma Crnich, Erik Sanchez, Mallory A. Havens, Daniel S. Kissel

There is currently an unmet demand for multi-functional precision treatments for Alzheimer's disease (AD) after several failed attempts at designing drugs based on the amyloid hypothesis. The focus of this work is to investigate sulfur-bridged quinoline ligands that could potentially be used in chelation therapies for a subpopulation of AD patients presenting with an overload of labile copper ions, which are known to catalyze the production of reactive oxygen species (ROS) and exacerbate other markers of AD progression. The ligands 1-(2′-thiopyridyl)isoquinoline (1TPIQ) and 2-(2′-thiopyridyl)quinoline (2TPQ) were synthesized and characterized before being electrochemically investigated in the presence of different oxidizing and reducing agents in solution with a physiological pH relevant to the brain. The electrochemical response of each compound with copper was studied by employing both hydrogen peroxide (H₂O₂) as an oxidizing agent and ascorbic acid (AA) as an antioxidant during analysis using cyclic voltammetry (CV). The cyclic voltammograms of each quinoline were compared with similar ligands that contained aromatic N-donor groups but no sulfur groups to provide relative electrochemical properties of each complex in solution. In a dose-dependent manner, it was observed that AA exerted dual-efficacy when combined with these chelating ligands: promoting synergistic metal binding while also scavenging harmful ROS, suggesting AA is an effective adjuvant therapeutic agent. Overall, this study shows how coordination by sulfur-bridged quinoline ligands can alter copper electrochemistry in the presence of AA to limit ROS production in solution.

Graphical abstract

在基于淀粉样蛋白假说设计药物的几次尝试失败后，目前对阿尔茨海默病（AD）的多功能精确治疗的需求尚未得到满足。这项工作的重点是研究硫桥喹啉配体，该配体可能用于AD患者亚群的螯合治疗，该亚群表现为不稳定铜离子过载，已知不稳定铜能催化活性氧（ROS）的产生并加剧AD进展的其他标志物。合成并表征了配体1-（2′-硫代吡啶基）异喹啉（1TPIQ）和2-（2′–硫代吡啶基异喹啉（2TPQ），然后在与大脑相关的生理pH的溶液中，在不同氧化剂和还原剂的存在下进行电化学研究。在使用循环伏安法（CV）进行分析期间，通过使用过氧化氢（H2O2）作为氧化剂和抗坏血酸（AA）作为抗氧化剂来研究每种化合物与铜的电化学响应。将每种喹啉的循环伏安图与含有芳香N-给体基团但不含硫基团的类似配体进行比较，以提供溶液中每种络合物的相对电化学性质。以剂量依赖性的方式，观察到AA与这些螯合配体结合时具有双重功效：促进协同金属结合，同时清除有害的ROS，这表明AA是一种有效的辅助治疗剂。总之，这项研究表明，在AA存在的情况下，硫桥喹啉配体的配位可以改变铜的电化学，从而限制溶液中ROS的产生。图形摘要

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引用次数: 0

Nickel chloride complexes with substituted 4′-phenyl-2′,2′:6′,2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions 取代4′-苯基-2′，2′：6′，2〃-联吡啶氯化镍配合物的合成、表征、抗增殖活性及生物分子相互作用

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-07-31 DOI: 10.1007/s00775-023-02011-3

Benwei Wang, Dameng Sun, Sihan Wang, Min Chen, Hongming Liu, Yanling Zhou, Hailan Chen, Zhen Ma

A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4′-(4-substituent phenyl)-2′,2′:6′,2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI–MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC₅₀ values of 0.223 μM and 0.335 μM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.

Graphical abstract

通过二氯化镍与10个4′-（4-取代苯基）-2′，2′:6′，2〃-联吡啶配体的反应，合成了一系列Ni（II）三明治状配位化合物，并通过元素分析、FT-IR、ESI–MS、固态紫外光谱和X射线单晶衍射分析对其结构进行了确证。三种人癌症细胞系和一种正常人细胞系用于抗增殖潜能研究：人癌症细胞系（A549）、人食管癌症细胞系（Eca-109）、人癌症细胞（Bel-7402）和正常人肝细胞（HL-7702）。结果表明，这些镍配合物对癌症细胞具有良好的抑制作用，优于临床常用的化疗药物顺铂。特别是配合物3（-甲氧基）和7（-氟）对Eca-109细胞系具有较强的抑制能力，IC50分别为0.223μM和0.335μM，配合物4和6表现出一定的细胞选择性，配合物6在控制浓度时可抑制癌症细胞，对正常细胞有轻微毒性。用紫外滴定法和CD光谱法研究了这些配合物与CT-DNA结合的能力，并用CD光谱法分析了配合物作用下BSA的二级结构变化。通过分子对接软件模拟了这些复合物与DNA、DNA Topo I和牛血清蛋白的结合，对接结果和最佳结合构象数据表明，它们以嵌入结合的方式与DNA相互作用，与实验结果一致。这些复合物在与DNA Topo I对接时更倾向于移动到切割位点，从而发挥酶切割的作用，而BSA通过与有效结合位点结合来促进复合物的作用。图形摘要

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引用次数: 0

Peroxidase activity of rice (Oryza sativa) hemoglobin: distinct role of tyrosines 112 and 151 水稻血红蛋白过氧化物酶活性:酪氨酸112和151的不同作用

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-07-29 DOI: 10.1007/s00775-023-02014-0

Valérie Derrien, Eric André, Sophie Bernad

Five non-symbiotic hemoglobins (nsHb) have been identified in rice (Oryza sativa). Previous studies have shown that stress conditions can induce their overexpression, but the role of those globins is still unclear. To better understand the functions of nsHb, the reactivity of rice Hb1 toward hydrogen peroxide (H₂O₂) has been studied in vitro. Our results show that recombinant rice Hb1 dimerizes through dityrosine cross-links in the presence of H₂O₂. By site-directed mutagenesis, we suggest that tyrosine 112 located in the FG loop is involved in this dimerization. Interestingly, this residue is not conserved in the sequence of the five rice non-symbiotic hemoglobins. Stopped-flow spectrophotometric experiments have been performed to measure the catalytic constants of rice Hb and its variants using the oxidation of guaiacol. We have shown that Tyrosine112 is a residue that enhances the peroxidase activity of rice Hb1, since its replacement by an alananine leads to a decrease of guaiacol oxidation. In contrast, tyrosine 151, a conserved residue which is buried inside the heme pocket, reduces the protein reactivity. Indeed, the variant Tyr151Ala exhibits a higher peroxidase activity than the wild type. Interestingly, this residue affects the heme coordination and the replacement of the tyrosine by an alanine leads to the loss of the distal ligand. Therefore, even if the amino acid at position 151 does not participate to the formation of the dimer, this residue modulates the peroxidase activity and plays a role in the hexacoordinated state of the heme.

Graphical abstract

在水稻(Oryza sativa)中鉴定出5种非共生血红蛋白(nsHb)。先前的研究表明，应激条件可以诱导它们过度表达，但这些珠蛋白的作用尚不清楚。为了更好地了解nsHb的功能，我们在体外研究了水稻Hb1对过氧化氢(H2O2)的反应性。我们的研究结果表明，重组水稻Hb1在H2O2存在下通过二酪氨酸交联进行二聚体化。通过定点诱变，我们认为位于FG环中的酪氨酸112参与了这种二聚化。有趣的是，这一残基在5种水稻非共生血红蛋白序列中并不保守。用愈创木酚氧化法测定了水稻Hb及其变体的催化常数。我们已经证明酪氨酸112是一种增强水稻Hb1过氧化物酶活性的残基，因为它被丙氨酸取代导致愈创木酚氧化减少。相反，酪氨酸151，一种隐藏在血红素口袋中的保守残基，降低了蛋白质的反应性。事实上，变体Tyr151Ala比野生型表现出更高的过氧化物酶活性。有趣的是，这种残基影响血红素的配位，酪氨酸被丙氨酸取代导致远端配体的丢失。因此，即使151位的氨基酸不参与二聚体的形成，该残基也能调节过氧化物酶的活性，并在血红素的六协调状态中发挥作用。图形抽象

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引用次数: 0

Ga(III) pyridinecarboxylate complexes: potential analogues of the second generation of therapeutic Ga(III) complexes? Ga(III)吡啶羧酸配合物:第二代治疗性Ga(III)配合物的潜在类似物?

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-07-27 DOI: 10.1007/s00775-023-02012-2

Michaela Rendošová, Róbert Gyepes, Simona Sovová, Danica Sabolová, Mária Vilková, Petra Olejníková, Martin Kello, Boris Lakatoš, Zuzana Vargová

A series of novel Ga(III)—pyridine carboxylates ([Ga(Pic)₃]·H₂O (GaPic; HPic = picolinic acid), H₃O[Ga(Dpic)₂]·H₂O (GaDpic; H₂Dpic = dipicolinic acid), [Ga(Chel)(H₂O)(OH)]₂·4H₂O (GaChel; H₂Chel = chelidamic acid) and [Ga(Cldpic)(H₂O)(OH)]₂ (GaCldpic; H₂Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H₂Dpic systems by potentiometry and ¹H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)₂]⁺ (logβ₀₂₁ = 16.23(6)), [Ga(Pic)₃] (logβ₀₃₁ = 20.86(2)), [Ga(Dpic)₂]⁻ (logβ₀₂₁ = 15.42(9)) and [Ga(Dpic)₂(OH)]²⁻ (logβ_-121 = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale ¹H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC₅₀ (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.

Graphical abstract

一系列新型Ga(III) -吡啶羧酸盐([Ga(Pic)3]·H2O (GaPic;HPic =吡啶酸)，h30 [Ga(Dpic)2]·H2O (GaDpic;H2Dpic =二吡啶酸)，[Ga(Chel)(H2O)(OH)]2·4H2O (GaChel;H2Chel =螯合酸)和[Ga(Cldpic)(H2O)(OH)]2 (GaCldpic;用简单的一步法合成了H2Cldpic = 4-氯二吡啶酸。振动光谱(中红外)、元素分析、热重分析和x射线衍射证实了配合物的分子结构、分子间和分子内相互作用及其对光谱和热性质的影响。此外，通过电位测定法和1H NMR谱法分别描述了Ga(III)-HPic和Ga(III)-H2Dpic体系中络合物的形态，并确定了单核络合物的形态;(Ga (Pic) 2) +(日志021年β= 16.23 (6)),(Ga (Pic) 3)(031年日志β= 20.86 (2)),(Ga (Dpic) 2)−(日志021年β= 15.42(9)和(Ga (Dpic) 2 (OH)) 2−(日志β-121 = 11.08(4))。为了确认配合物在1% DMSO(生物实验的主要溶剂)中的稳定性，测定了时间尺度1H NMR谱(溶出96 h后立即测定)。通过IC50 (0.05 mM)评估GaDpic和GaCldpic对难以治疗和多重耐药的铜绿假单胞菌的抑菌活性。另一方面，GaPic复合物对Jurkat、MDA-MB-231和A2058癌细胞系最有效，并且在75 μM和100 μM浓度下，在相对较短的时间内(最多48 h)显著降低HepG2癌细胞的活力。此外，荧光测量已用于阐明配体、Ga(III)复合物和牛血清白蛋白之间的结合活性。图形抽象

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引用次数: 0

The adducts of cyano- and aquacobalamin with hypochlorite 氰基和水产养殖用氯酸盐的加合物

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-07-26 DOI: 10.1007/s00775-023-02015-z

Maria Lehene, Adrian M. V. Brânzanic, Radu Silaghi-Dumitrescu

Hypochlorite is known to oxidatively degrade the corrin ring of cobalamin. Here, transient reaction intermediates are described in the reaction of aqua as well as of cyano-cobalamin with hypochlorite, using stopped-flow UV–vis kinetics. For aqua-cobalamin, the intermediate is assigned as arising from substitution of the aqua ligand with hypochlorite. For cyano-cobalamin, the intermediate is proposed to arise from substitution of the benzimidazole ligand trans to the cyanide. In both cases, the intermediates would feature a new Co(III)-OCl⁻bond—which is also supported by density functional theory (DFT) calculations.

Graphical abstract

已知次氯酸盐氧化降解钴胺素的corrin环。在这里，瞬态反应中间体描述了水的反应，以及氰钴胺素与次氯酸盐的反应，使用停流紫外可见动力学。对于水钴胺素，中间体是由次氯酸盐取代水配体产生的。对于氰钴胺素，中间体是由苯并咪唑配体反式取代氰化物而产生的。在这两种情况下，中间产物都有一个新的Co(III)-OCl−键，这也得到了密度泛函理论(DFT)计算的支持。图形抽象

引用次数: 0

meso-Bromination of cyano- and aquacobalamins facilitates their processing into Co(II)-species by glutathione 氰基和水产balbalamine的介溴化促进了它们被谷胱甘肽加工成Co(II)-物种

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-07-22 DOI: 10.1007/s00775-023-02009-x

Ilia A. Dereven’kov, Vladimir S. Osokin, Ilya A. Khodov, Valentina V. Sobornova, Nikita A. Ershov, Sergei V. Makarov

Cyanocobalamin (CNCbl), a medicinal form of vitamin B₁₂, is resistant to glutathione (GSH), and undergoes intracellular processing via reductive decyanation producing the Co(II)-form of Cbl (Cbl(II)) mediated by the CblC-protein. Alteration of the CblC-protein structure might inhibit CNCbl processing. Here, we showed that introducing a bromine atom to the C10-position of the CNCbl corrin ring facilitates its reaction with GSH leading to the formation of Cbl(II) and cyanide dissociation. In a neutral medium, the reaction between C10-Br-CNCbl and GSH proceeds via the complexation of the reactants further leading to dimethylbenzimidazole (DMBI) substitution and electron transfer from GSH to the Co(III)-ion. The reaction is accelerated upon the GSH thiol group deprotonation. The key factors explaining the higher reactivity of C10-Br-CNCbl compared with unmodified CNCbl towards GSH are increasing the electrode potential of CNCbl two-electron reduction upon meso-bromination and the substantial labilization of DMBI, which was shown by comparing their reactions with cyanide and the pK_a values of DMBI protonation (pK_{a base-off}). Aquacobalamin (H₂OCbl) brominated at the C10-position of the corrin reacts with GSH to give Cbl(II) via GSH complexation and subsequent reaction of this complex with a second GSH molecule, whereas unmodified H₂OCbl generates glutathionyl-Cbl, which is resistant to further reduction by GSH.

Graphical abstract

氰钴胺素(CNCbl)是维生素B12的一种药物形式，对谷胱甘肽(GSH)具有抗性，并通过还原性脱氰作用在细胞内产生Co(II)-形式的Cbl(Cbl(II))，由cblc蛋白介导。cblc蛋白结构的改变可能会抑制CNCbl的加工。在这里，我们发现在CNCbl环的c10位置上引入一个溴原子有助于其与谷胱甘肽的反应，从而形成Cbl(II)和氰化物解离。在中性介质中，C10-Br-CNCbl与GSH之间的反应通过反应物的络合进行，进一步导致二甲基苯并咪唑(DMBI)取代和电子从GSH转移到Co(III)-离子。谷胱甘肽巯基去质子化加速了反应。C10-Br-CNCbl与未改性CNCbl相比，对GSH具有更高的反应活性，其关键因素是CNCbl在中溴化过程中双电子还原的电极电位增加，以及DMBI的大量稳定，这一点通过与氰化物的反应和DMBI质子化的pKa值(pKa碱基)的比较得到了证明。在corrin的c10位溴化的Aquacobalamin (H2OCbl)与GSH反应，通过GSH络合和随后与第二个GSH分子的反应产生Cbl(II)，而未修饰的H2OCbl产生谷胱甘肽-Cbl，它抵抗GSH的进一步还原。图形抽象

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引用次数: 0

Interactions of arene ruthenium(II) complexes [η6-(C6H6)Ru(pprip)Cl]+ and [η6-(C6H6)Ru(H2iiP)Cl]+ with RNA triplex poly(U)•poly(A)*poly(U) 芳烃钌(II)配合物[η6-(C6H6)Ru(pprip)Cl]+和[η6-(C6H6)Ru(H2iiP)Cl]+与RNA三元聚(U)•聚(A)*聚(U)的相互作用

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-07-21 DOI: 10.1007/s00775-023-02008-y

Feng Yuan, Xiaohua Liu, Juan Li, Lifeng Tan

Two arene ruthenium(II) complexes [η⁶-(C₆H₆)Ru(pprip)Cl]PF₆ (Ru1; pprip = 2-(3-phenyl-1H-pyrazol-4-yl)-imidazolo[4,5-f][1,10]phenanthroline) and [η⁶-(C₆H₆)Ru(H₂iiP)Cl]PF₆ (Ru2; H₂iiP = 2-(indole-3-yl)-imidazolo[4,5-f][1,10]phenanthroline) have been synthesized and characterized in this work. Binding properties of Ru1 and Ru2 with the triplex RNA poly(U)•poly(A)*poly(U) were investigated by spectrophotometry and spectrofluorometry as well as viscosimetry. Analysis of spectroscopic titrations and viscosity measurements show that the two complexes bind with the triplex through intercalation, while the binding affinity for Ru2 toward the triplex is stronger than that for Ru1. Melting experiments indicate that the stabilizing effects of Ru1 and Ru2 toward the triplex differ from each other. Under the conditions used herein, Ru1 only stabilizes the Hoogsteen base-paired strand (third strand) without affecting stabilization of the Watson–Crick base-paired strand (the template duplex) of the triplex, while Ru2 stabilizes both the template duplex and the third strand. Although the two complexes prefer to stabilizing the third strand rather than the template duplex, the third-strand stabilization effect of Ru2 is stronger than that of Ru1. The obtained results of this work reveal that the planarity of the intercalative ligands plays an important role in the triplex stabilization by arene Ru(II) complexes.

Graphical abstract

二芳烃钌(II)配合物[η6-(C6H6)Ru(pprip)Cl]PF6 (Ru1;pprip = 2-(3-苯基- 1h -吡唑-4-基)-咪唑啉[4,5-f][1,10]菲罗啉]和[η6-(C6H6)Ru(H2iiP)Cl]PF6 (Ru2;H2iiP = 2-(吲哚-3-基)-咪唑[4,5-f][1,10]菲罗啉]的合成和表征。采用分光光度法、荧光光谱法和粘度法研究了Ru1和Ru2与三重RNA poly(U)•poly(A)*poly(U)的结合特性。光谱滴定分析和粘度测量表明，这两个配合物通过插层与三联体结合，而Ru2对三联体的结合亲和力比Ru1强。熔融实验表明，Ru1和Ru2对三相体的稳定作用不同。在本文使用的条件下，Ru1仅稳定Hoogsteen碱基配对链(第三链)，而不影响三联体中Watson-Crick碱基配对链(模板双链)的稳定，而Ru2稳定模板双链和第三链。虽然这两种配合物更倾向于稳定第三链而不是模板双链，但Ru2的第三链稳定作用强于Ru1。研究结果表明，嵌入配体的平面性对芳烃Ru(II)配合物的三络合物稳定起着重要的作用。图形抽象

{"title":"Interactions of arene ruthenium(II) complexes [η6-(C6H6)Ru(pprip)Cl]+ and [η6-(C6H6)Ru(H2iiP)Cl]+ with RNA triplex poly(U)•poly(A)*poly(U)","authors":"Feng Yuan, Xiaohua Liu, Juan Li, Lifeng Tan","doi":"10.1007/s00775-023-02008-y","DOIUrl":"10.1007/s00775-023-02008-y","url":null,"abstract":"<div><p>Two arene ruthenium(II) complexes [<i>η</i><sup>6</sup>-(C<sub>6</sub>H<sub>6</sub>)Ru(pprip)Cl]PF<sub>6</sub> (Ru<b>1</b>; pprip = 2-(3-phenyl-1H-pyrazol-4-yl)-imidazolo[4,5-<i>f</i>][1,10]phenanthroline) and [<i>η</i><sup>6</sup>-(C<sub>6</sub>H<sub>6</sub>)Ru(H<sub>2</sub>iiP)Cl]PF<sub>6</sub> (Ru<b>2</b>; H<sub>2</sub>iiP = 2-(indole-3-yl)-imidazolo[4,5-<i>f</i>][1,10]phenanthroline) have been synthesized and characterized in this work. Binding properties of Ru<b>1</b> and Ru<b>2</b> with the triplex RNA poly(U)•poly(A)*poly(U) were investigated by spectrophotometry and spectrofluorometry as well as viscosimetry. Analysis of spectroscopic titrations and viscosity measurements show that the two complexes bind with the triplex through intercalation, while the binding affinity for Ru<b>2</b> toward the triplex is stronger than that for Ru<b>1</b>. Melting experiments indicate that the stabilizing effects of Ru<b>1</b> and Ru<b>2</b> toward the triplex differ from each other. Under the conditions used herein, Ru<b>1</b> only stabilizes the Hoogsteen base-paired strand (third strand) without affecting stabilization of the Watson–Crick base-paired strand (the template duplex) of the triplex, while Ru<b>2</b> stabilizes both the template duplex and the third strand. Although the two complexes prefer to stabilizing the third strand rather than the template duplex, the third-strand stabilization effect of Ru<b>2</b> is stronger than that of Ru<b>1</b>. The obtained results of this work reveal that the planarity of the intercalative ligands plays an important role in the triplex stabilization by arene Ru(II) complexes.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 6","pages":"559 - 570"},"PeriodicalIF":3.0,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4824316","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}

引用次数: 1

Ferrocene-based nitroheterocyclic sulfonylhydrazones: design, synthesis, characterization and trypanocidal properties 二茂铁基硝基杂环磺酰腙:设计、合成、表征和锥虫特性

IF 3 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry

Pub Date : 2023-07-18 DOI: 10.1007/s00775-023-02010-4

Miguel Gallardo, Rodrigo Arancibia, Claudio Jiménez, Shane Wilkinson, Patricia M. Toro, Pascal Roussel, Natacha Henry

A series of new ferrocenyl nitroheterocyclic sulfonylhydrazones (1a–4a and 1b–2b) were prepared by the reaction between formyl (R = H) or acetyl (R = CH₃) nitroheterocyclic precursors [4/5-NO₂(C₅H₂XCOR), where X = O, S)] and ferrocenyl tosyl hydrazine [(η⁵-C₅H₅)Fe(η⁵-C₅H₄SO₂-NH-NH₂)]. All compounds were characterized by conventional spectroscopic techniques. In the solid state, the molecular structures of compounds 1a, 2b, and 3a were determined by single-crystal X–ray diffraction. The compounds showed an E-configuration around the C=N moiety. Evaluation of trypanocidal activity, measured in vitro against the Trypanosoma cruzi and Trypanosoma brucei strains, indicated that all organometallic tosyl hydrazones displayed activity against both parasite species with a higher level of potency toward T. brucei than T. cruzi. Moreover, the biological evaluation showed that the 5-nitroheterocyclic derivatives were more efficient trypanocidal agents than their 4-nitroheterocyclic counterparts.

Graphical abstract

通过甲酰基(R = H)或乙酰基(R = CH3)硝基杂环前体[4/5-NO2(C5H2XCOR)，其中X = O, S)]与二茂铁基甲酰肼[(η5-C5H5)Fe(η5-C5H4SO2-NH-NH2)]的反应，制备了一系列新的二茂铁基硝基磺酰腙(1a-4a和1b-2b)。所有化合物都用常规的光谱技术进行了表征。在固体状态下，化合物1a、2b和3a的分子结构通过单晶x射线衍射测定。化合物在C=N附近呈e型构型。体外对克氏锥虫和布鲁氏锥虫的杀虫活性评价表明，所有有机金属甲酰腙对这两种寄生虫都有活性，对布鲁氏锥虫的效力高于对克氏锥虫的效力。此外，生物学评价表明，5-硝基杂环衍生物比4-硝基杂环衍生物是更有效的锥虫剂。图形抽象

{"title":"Ferrocene-based nitroheterocyclic sulfonylhydrazones: design, synthesis, characterization and trypanocidal properties","authors":"Miguel Gallardo, Rodrigo Arancibia, Claudio Jiménez, Shane Wilkinson, Patricia M. Toro, Pascal Roussel, Natacha Henry","doi":"10.1007/s00775-023-02010-4","DOIUrl":"10.1007/s00775-023-02010-4","url":null,"abstract":"<div><p>A series of new ferrocenyl nitroheterocyclic sulfonylhydrazones (<b>1a</b>–<b>4a</b> and <b>1b</b>–<b>2b</b>) were prepared by the reaction between formyl (R = H) or acetyl (R = CH<sub>3</sub>) nitroheterocyclic precursors [4/5-NO<sub>2</sub>(C<sub>5</sub>H<sub>2</sub>XCOR), where X = O, S)] and ferrocenyl tosyl hydrazine [(η<sup>5</sup>-C<sub>5</sub>H<sub>5</sub>)Fe(η<sup>5</sup>-C<sub>5</sub>H<sub>4</sub>SO<sub>2</sub>-NH-NH<sub>2</sub>)]. All compounds were characterized by conventional spectroscopic techniques. In the solid state, the molecular structures of compounds <b>1a</b>, <b>2b</b>, and <b>3a</b> were determined by single-crystal X–ray diffraction. The compounds showed an <i>E</i>-configuration around the C=N moiety. Evaluation of trypanocidal activity, measured in vitro against the <i>Trypanosoma cruzi</i> and <i>Trypanosoma brucei</i> strains, indicated that all organometallic tosyl hydrazones displayed activity against both parasite species with a higher level of potency toward <i>T. brucei</i> than <i>T. cruzi</i>. Moreover, the biological evaluation showed that the 5-nitroheterocyclic derivatives were more efficient trypanocidal agents than their 4-nitroheterocyclic counterparts.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 6","pages":"549 - 558"},"PeriodicalIF":3.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4722096","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}

引用次数: 0