The synthesis, structural characterization, spectroscopic features, solubility, and anti-inflammatory properties of a novel manganese(II)-creatine coordination polymer, {[Mn(μ2-CRN)2(H2O)2](NO3)2·2H2O}n (CRN = creatine), are reported. Single-crystal X-ray diffraction revealed a one-dimensional coordination polymer crystallizing in the triclinic system (P1¯), in which the Mn2+ center resides on a crystallographic inversion center and adopts a regular octahedral geometry defined by four carboxylate oxygen atoms from four syn-syn μ2-bridging CRN ligands and two trans-aqua ligands; adjacent Mn2+ centers are doubly bridged along the crystallographic a axis (Mn⋯Mn = 4.7085 Å). Hirshfeld surface analysis demonstrated that the framework is dominated by O⋯H/H⋯O and N⋯H/H⋯N contacts, yielding compact packing with only 6.37% void volume. Periodic density functional theory calculations supported the assignment of Raman and infrared vibrational modes. Thermal analyses revealed a three-stage decomposition (25-400 °C) involving sequential loss of lattice water, coordinated water, nitrate, and organic ligand. In vitro anti-inflammatory evaluation against lipopolysaccharide-stimulated RAW 264.7 macrophages showed no cytotoxicity up to 50 μM and an inverse concentration-dependent inhibition of nitric oxide production (maximal reduction of 25 ± 2% at 0.78 μM). Cell-free control experiments confirmed that nitrate counterions do not contribute to nitrite generation or interfere with the Griess reaction, validating the biological origin of the observed inhibition. Aqueous solubility was determined experimentally as 1.00 mM (0.514 g/L) at 25 °C, and in silico pharmacokinetic parameters indicate low gastrointestinal absorption, absence of P-glycoprotein substrate behavior, and no cytochrome inhibition, positioning this bioinspired compound for further mechanistic investigation of inflammatory pathways.

Acyl thioureas are versatile organosulfur scaffolds with broad relevance in coordination chemistry and functional applications, driven by their structural flexibility and the presence of both hard and soft donor sites. This enables the formation of diverse metal complexes with tunable properties. This review provides a critical overview of recent advances (2024-2026) in their synthesis, conformational features, coordination behavior, and applications. Emphasis is placed on structure-activity and coordination-property relationships, highlighting how substituent effects and coordination modes influence biological, catalytic, and agrochemical performance. In addition, coordination behavior is systematically classified to improve understanding of structure-function correlations. The current review integrates recent experimental and computational findings to identify key trends and challenges, offering insights for the rational design of acyl thiourea-based systems for advanced applications.

Adenosylcobalamin (AdoCbl) shows different photochemical behavior when free in solution compared to when it is bound to the photoregulatory protein CarH. In both cases, the initial photoproduct is cob(II)alamin and the 5'-deoxyadenosyl radical (Rios-Santacruz et al., Nature, 2026, 650, 1045-1052). However, in solution, the ultimate products are cob(II)alamin and the cyclic product, 5',8-cycloadenosine, while in the CarH protein, cob(I)alamin and the exocyclic methylene product 4',5'-anhydroadenosine are formed. This has led to speculation that alkene formation in CarH plays a protective role, preventing deleterious reactions of the 5'-deoxyadenosyl radical. Recently, we have found that the CarH-type reactivity (formation of alkene + cob(I)alamin) is not in fact unusual; we find this behavior across a range of alkylcobalamins (alkylCbls) (Mukherjee et al., Chem. Sci., 2026, 17, 5518-5531). In order to explore the factors driving these contrasting outcomes, we have characterized the photolytic reactivity of AdoCbl, both in a variety of solvents as well as in several AdoCbl-dependent proteins. In no case do we find evidence for CarH-type reactivity, even under conditions where other alkylCbls consistently generate cob(I)alamin + alkene. These findings indicate that the anomalous CarH behavior may be better understood not as CarH enforcing unusual reactivity on the cobalamin, but rather as CarH enabling the intrinsic alkyl-radical behavior that is otherwise quenched when the 5'-deoxyadenosyl radical is free in solution or bound in regular cobalamin-dependent proteins.

This is the first part of a three-part review of advances in cobalt corrinoid (B12) research published between 2020 and 2025, focusing on the chemistry and industrial production of cobalt corrinoids. Although vitamin B12 is widely recognised for its biological and clinical importance, its derivatives also constitute a distinctive class of organometallic compounds whose behaviour emerges from the interplay between cobalt redox chemistry, corrin macrocycle structure, and axial ligation. Recent work increasingly treats corrinoids not as structurally conserved cofactors with narrowly defined functions, but as chemically adaptable, context-dependent systems whose properties are strongly shaped by molecular environment and speciation. Advances in analytical chemistry, particularly speciation-resolved methodologies, have clarified the functional significance of corrinoid diversity while exposing the limitations of bulk analytical approaches. Parallel developments in inorganic, structural, physical, and photochemical studies have refined understanding of how coordination environment governs electronic structure, reactivity, excited-state behaviour, and CoC bond homolysis. At the same time, synthetic chemistry, catalysis, and materials science have expanded corrinoid function into other fields, enabling applications in electrocatalysis, hybrid materials, and responsive systems. Studies of industrial production further illustrate the importance of chemical control over cofactor maturation, ligand assembly, and redox balance. These developments establish a chemical framework in which corrinoid behaviour is best understood as emergent from speciation, structure, and environment, providing the foundation for subsequent analyses of B12 biochemistry and microbiology (Part 2) and B12 and health (Part 3).

Naphthyl-functionalized half-sandwich Ir(III) complexes were designed as non‑platinum metal candidates for colorectal cancer cell growth inhibition, the naphthyl group was purposefully introduced in the ligands in order to facilitate DNA intercalation and enhancing biomolecular interactions. In this work, eight naphthyl-functionalized half-sandwich Ir(III) complexes (L-Ir(cp)Cl) [cp = pentamethylcyclopentadienyl] (C1a-C4a, C1b-C4b) were designed and synthesized bearing central pyridine- or pyrimidine-based N, N-chelating ligands. The target complexes were obtained in high yields via simple single step reaction and characterized by [1]H NMR, [13]C NMR, UV-vis, IR spectroscopy and high-resolution mass spectrometry (HR-MS). The structures of six complexes (C3a-C4a, C1b-C4b) were determined by single-crystal X-ray analysis, showing a typical half-sandwich "three-legged piano-stool" geometry with a chloride ancillary ligand (Ir-Cl), which may be relevant to their biological activity. In vitro antiproliferative activity was assessed in colorectal cancer RPMI 4788 and LOVO cells via MTT assays. In both these series C1b and C2b exhibited potent proliferation-inhibitory effects, with stronger activity in RPMI 4788 cells, and C2b outperforming C1b. Cancer cell imaging, flow cytometry, and clonogenic assays confirmed strong inhibition of cell proliferation. Concentration- and time-dependent migration assays showed significantly reduced cancer cell migration. Cell-cycle analysis suggested S-phase accumulation in RPMI 4788 cells, and C2b treatment decreased the expression of Cyclin D1 and CDK4. Western blot analysis revealed changes in the representative proteins associated with apoptosis and cell growth, including PARP, Caspase-3, Bcl-2, AKT, and mTOR. This study provided experimental evidence supporting these novel Ir(III) complexes, especially C2b as potential in vitro antiproliferative agents in colorectal cancer cells that need to be further explored in other cancers by detailed in vitro and in vivo mechanistic investigations.

Rhenium tricarbonyl complexes in their monometallic forms have been extensively studied, mainly for their potent inhibitory activity against cancer cells. However, far fewer dinuclear complexes have been investigated for similar applications. In this study, we report the synthesis, crystal structure, DFT analysis, in vitro biological screening, and in silico molecular docking of the complex NEt4[{Re(CO)3}2-μ-(OCH3)2-μ-(3,5-Me2py)], C1 (where OCH3 = methoxy; 3,5-Me2py = 3,5-dimethyl-1H-pyrazolate). This dinuclear complex, C1, was characterised spectroscopically by FT-IR, 1H and 13C NMR, UV-Vis, as well as single-crystal X-ray diffraction. Preliminary in vitro screening at a single dose of 10 μM in DMSO revealed excellent cytotoxicity of C1 against cervical (HeLa and CaSki), pancreatic (PANC-1 and CFPAC-1), and breast (MCF-7) cancer cell lines. It was further evaluated for its half-maximal inhibitory concentration (IC50) which was determined as 1.59 ± 0.34 (SI = 6.39), 1.06 ± 0.35 (SI = 9.59), 0.74 ± 0.22 (SI = 13.73), 3.58 ± 0.10 (SI = 2.83) and 2.24 ± 0.45 (SI = 4.54) μM against HeLa, CaSki, CFPAC-1, PANC-1 and MCF-7, respectively, while the IC50 against MRC-5 (non-cancerous human fibroblast cells) was 10.16 ± 0.8 μM. The DFT calculations indicated that C1 is both reactive and conductive, with an energy gap (EHOMO-ELUMO) of 4.11 eV. Additionally, C1 was docked against tubulin to illustrate its potential binding modes to the target tubulin, and the in silico molecular docking results revealed binding affinities ranging from -5.43 to -4.37 kcal/mol.

Cancer is the second leading cause of death worldwide. Treatment options such as conventional chemotherapeutic agents often have significant shortcomings. To address such treatment modalities, ruthenium(III) prodrugs offer promise as anticancer agents with superior efficacy. Fuelled by this ongoing research, this work evaluates lantern-type diruthenium(II,III) complexes against ER + ve MCF-7 and triple-negative MDA-MB-231 breast cancer cells. Stoichiometric reactions of unsymmetrical N,N'-anilinopyridinate (R-ap) ligands with [Ru2(O2CCH3)4Cl] yielded five mono-substituted anilinopyridinate trisacetatochlorodiruthenium(II,III) complexes, ([Ru2(O2CCH3)3(R-ap)Cl]) (C1 - C5; R = H, 2-CH3, 4-CH3, 2-F, and 4-F) in moderate yields. All ligands and complexes are fully characterised using spectroscopic and analytical techniques, with assignments matching literature data. Crystal structures of C1, C3 and C5 show lantern-type structures in triclinic space groups. Complexes maintain their paramagneticity with magnetic moments 3.50 μB (C1), 3.64 μB (C3), 3.85 μB (C4) and 4.10 μB (C5), respectively, indicative of three unpaired electrons in the π* and δ* orbitals. Free R-ap ligands exhibited negligible cytotoxicity against human breast MCF-7 and MDA-MB-231 cancers, while coordination to the Ru2[5+] cores enhanced their solubility and efficacy over the precursor [Ru2(O2CCH3)4Cl]. C3 and C5 show promising cytotoxicity against MCF-7 cells (IC50: 39.0 μM and 49.1 μM), outperforming cisplatin in selectivity for MCF-7 cancer cells. C3 induces DNA damage, the cell cycle (p53), and apoptosis (caspase 9 and poly (ADP-ribose) polymerase protein (PARP)). Altogether, these results suggest that [Ru2(O2CCH3)3(R-ap)Cl] complexes show promising anticancer properties against MCF-7 human breast cancer cells. Additionally, the possible mechanisms of action of [Ru2(O2CCH3)3(R-ap)Cl] complexes were highlighted.

Dormant spores of manganese-oxidizing Bacillus sp. oxidize dissolved manganese, producing insoluble manganese oxide mineral. Many of them do so with the help of Mnx-a protein complex of a catalytically active multicopper oxidase enzyme MnxG bound to accessory proteins MnxE and MnxF-in a two-step reaction process, first oxidizing Mn(II) to Mn(III), then converting Mn(III) to the nanoparticulate MnO2 product. In this report, the effect of Ca[2+] ions on manganese biomineralization by Mnx from Bacillus sp. PL-12 is investigated by spectroscopic kinetic assays. The sigmoidal shape of the enzymatic progress curves is unaffected by Ca[2+], indicating that the enzymatic mechanism is preserved. The rate of the overall reaction increases up to ∼10 μM of Ca[2+], and then decreases. The Mn(III) trapping agent, pyrophosphate, was used to investigate the effect of Ca[2+] on the two individual reaction steps. The acceleration/deceleration sequence with ∼10 μM Ca[2+] optimum occurs during the conversion of Mn(III) to Mn(IV). The Mn(III)/Mn(IV) turnover rate shows a cooperative dependence on the Ca[2+] concentration, indicating that two Ca[2+] act simultaneously. The oxidation to the final Mn(IV) product is known to proceed via disproportionation of a Mn(III)(μ-OH)2Mn(III) intermediate. We propose that the resulting Mn(IV)(μ-O)2Mn(IV) dimers assemble tetramers via additional oxo bridge formation, a process promoted by Ca[2+]. Maturation of the tetramers via further polymerization is likewise promoted by Ca[2+]. A stoichiometry of 0.5Ca/Mn is seen for the Ca-induced shift in the Mn(III)/Mn(IV) equilibrium, indicating the binding of 1 Ca for every 2 Mn in the Mnx-produced MnO2 nanoparticles.

Vitamin B12 (cobalamin) is an essential micronutrient whose biological importance extends beyond its traditional classification as a haematinic vitamin. This third and final part of a review covering work published between 2020 and 2025 synthesises selected illustrative studies that have advanced understanding of B12 physiology, nutrition, deficiency, delivery, and systems-level biology. At the molecular level, B12 functions as a cofactor in one‑carbon metabolism and mitochondrial pathways, influencing DNA synthesis, methylation capacity, and energy metabolism. These biochemical roles translate into organism-level consequences, particularly in the nervous system, where deficiency may cause irreversible neurological injury even in the absence of overt haematological abnormalities.Population-level analyses show that B12 status reflects the interaction of didetary intake, absorption efficiency, life stage, and food-system dynamics. Although animal-source foods remain the most reliable sources, shifts towards plant-based diets and inconsistent fortification practices are altering risk profiles. Clinical evidence further indicates that B12 deficiency is heterogeneous, frequently under-recognised, and complicated by the limitations of conventional biomarkers. Advances in delivery science point towards more controlled and targeted interventions, including encapsulation technologies, alternative administration routes, and receptor-mediated transport strategies. Emerging evidence also suggests biological activities for cobalamin derivatives beyond classical cofactor function, while microbiome research increasingly implicates corrinoid metabolism in host-microbe interactions relevant to immune and metabolic regulation. These developments support an integrated systems-level view of B12 biology spanning dietary supply, physiology, microbial ecology, and therapeutic innovation. SYNOPSIS: The final part of this review examines recent advances in vitamin B12 biology, spanning physiology, nutrition, deficiency, biomarker limitations, therapeutic delivery, and microbiome-linked corrinoid metabolism. These developments support an integrated systems-level view linking molecular function, dietary ecology, population health, and emerging therapeutic opportunities.

Ovarian cancer treatment has long been challenged by clinical obstacles including platinum resistance recurrence and incomplete eradication of micrometastatic lesions. This study presents a platinum(II)-based compound AP-604 through the "Targeted Drug Conjugate (TDC)" strategy to overcome the limitations inherent in conventional chemotherapy. Research indicated that AP-604 preserved potent PIKfyve targeting capability (IC50 = 15.4 ± 1.3 nM) while also exhibiting pronounced cytotoxicity against A2780 (IC50 = 2.2 ± 0.4 μM). Mechanistic investigations revealed a multi-mode antitumor action involving concurrent activation of the BCL-2/caspase-dependent apoptotic pathway and S phase specific cell cycle arrest, complemented by enhanced platinum accumulation that exacerbated DNA damage. In vivo tests showed that AP-604 at a high dose achieved stronger tumor suppression than Cisplatin, Apilimod, and their combination without inducing significant histopathological damage. These findings proved that AP-604 has potential as a promising drug candidate with enhanced efficacy and favorable safety profiles in treatment of ovarian cancer.

Radiometal-based radiopharmaceuticals have become central to the advancement of molecular imaging and targeted radionuclide therapy, offering powerful tools for the diagnosis and treatment of diseases affecting the brain. The unique chemical versatility of radiometals - encompassing a broad range of coordination chemistries, physical half-lives, and emission properties - combined with an expanding repertoire of targeting biomolecules enables highly tunable and increasingly modular imaging and therapeutic platforms. In particular, positron emission tomography (PET) using radiometal-labelled tracers provides sensitive, quantitative, and non-invasive assessment of molecular processes in vivo, while radiometal-based therapeutic agents enable the selective delivery of cytotoxic radiation to diseased tissue. This review examines recent progress in the application of radiometal-based radiopharmaceuticals for brain disorders, with a focus on neuro-oncology - including primary brain tumours and brain metastases - as well as neurodegenerative diseases such as Alzheimer's disease and Parkinsons disease. Key challenges unique to brain applications are discussed, including the restrictive nature of the blood-brain barrier, heterogeneous target expression, and off-target biodistribution. Recent advances in chelator development, emerging antigen targets, alternative routes of administration, and strategies to improve brain delivery are highlighted. While imaging agents continue to lead therapeutic development in this space, reflecting the need for accurate disease characterisation, recent progress underscores the potential of radiometal-based therapies for brain disease. In particular, immunoPET has emerged as a powerful tool for evaluating target expression, biodistribution, and treatment response. Collectively, these developments position radiometal-based radiopharmaceuticals as a promising and evolving platform enabling personalised treatment strategies for neurological disorders.

In this Part 2 of a three-part review of advances in cobalt corrinoid research published between 2020 and 2025, we examine the biochemistry and microbiology of the cobalt corrinoids. Central to this literature is the chemical complementarity between cobalt and the corrin macrocycle, which enables distinct catalytic strategies including methyl transfer, radical rearrangement, reductive dehalogenation, and hybrid radical-SAM transformations. Recent work shows that corrinoid-dependent enzymes do not merely exploit intrinsic cobalt reactivity, but actively shape it through structural, electronic, and kinetic control over Co-C bond activation, intermediate stabilisation, and reaction selectivity. Equally prominent is the requirement for rigorous cofactor management, as corrinoid chemistry remains vulnerable to oxidative damage, misligation, and incomplete cofactor maturation, necessitating specialised systems for trafficking, remodelling, repair, and selective deployment. Genomic, evolutionary, and ecological studies further reveal that corrinoid metabolism is unevenly distributed, with widespread auxotrophy, selective transport, and cobamide exchange creating extensive metabolic interdependence within microbial communities. These patterns reflect evolutionary partitioning of biosynthetic capacity while emphasising the importance of environmental constraints, particularly cobalt availability and horizontal gene transfer, in shaping corrinoid cycling. In host-associated systems, corrinoid availability influences metabolic flux, microbial community structure, and functional outputs with implications for host physiology. Corrinoid metabolism emerges from this literature as a multiscale biological system in which inorganic chemistry, enzyme architecture, genomic organisation, and ecological context are functionally intertwined.

3-substituted derivatives of picolinic acid, 3-methylpicolinic acid (3-MePicH) and 3-hydroxypicolinic acid (3-OHPicH), were used to investigate their complex-forming, structural, spectral, and thermal properties toward biologically active silver(I) and zinc(II) ions. In the case of the 3-MePicH ligand, potentiometric and [1]H NMR titrations confirmed the formation of complex species [Ag(3-MePic)], [Zn(3-MePic)][+], and [Zn(3-MePic)2]. In contrast, the 3-OHPicH ligand was incorporated into the coordination sphere of the Ag(I) and Zn(II) central atoms only in the form of protonated complex species. Under ecofriendly conditions, the complexes were isolated in solid state; their IR, NMR, thermal analyses, molar conductivity and for the zinc(II) complex with the 3-methylpicolinate ligand also single-crystal analysis confirmed their composition: [Ag(3-MePic)]·0.5H2O (Ag3-MePic), [Zn(3-MePic)2(H2O)] (Zn3-MePic), [Ag(3-OHPic)] (Ag3-OHPic), [Zn(3-OHPic)2(H2O)2] (Zn3-OHPic). The stability of the investigated complexes in biologically relevant solvents made it possible to evaluate their antimicrobial and anticancer activity. Compared with AgPic (the analogous silver(I) complex with picolinic acid), a more significant antibacterial and antifungal activity for Ag3-OHPic was confirmed, as well as higher cytotoxicity for both pyridine-substituted silver(I) complexes against A549 (36.3 μM) and Jurkat (37.8 μM) cells. The interactions of the silver(I) complexes with human serum albumin and calf thymus DNA were also investigated, followed by an evaluation of their potential inhibitory effects on human topoisomerases I and II. Among the tested compounds, Ag3-MePic exhibited the most pronounced inhibitory activity against Topoisomerase II at a concentration of 0.5 μM.

Physicochemical and biological properties of four cadmium(II) coordination complexes with 4-methyl-5-imidazolecarboxaldehyde, differing in their inner-sphere halide anions: Cl[-] (Cd-1), Br[-] (Cd-2), I[-] (Cd-3), or the PF6[-] counterion of the outer-sphere (Cd-4). The electrochemical characteristics of the tested compounds in Tris-HCl buffer were determined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), and nucleation was observed at the electrode surface. Isothermal titration calorimetry data revealed that the investigated complexes exhibit relatively high binding affinity for a specific site on bovine serum albumin, with the chloride complex achieving the highest value. These interactions occur at different stoichiometries, primarily driven by favorable enthalpic interactions. However, these binding interactions did not alter the protein's secondary structure. In vitro biological assays demonstrated potent and selective antifungal activity against Candida species, including fluconazole-resistant isolates, with MIC50 values as low as 0.75 μM, while antibacterial effects were negligible. Cytotoxicity toward human A-549 and MCF-7 cell lines was moderate, yielding selectivity indices exceeding 10 for the most active antifungal coordination compound. Molecular docking studies involving CYP51 from Candida albicans and Candida glabrata suggest that this enzyme might be a molecular target of the described cadmium coordination compounds and that disruption of ergosterol biosynthesis might contribute to their observed antifungal activity. These findings highlight the potential of Cd(II)-imidazole derivative systems as selective antifungal agents and underscore the relevance of metal-ligand coordination in tuning bioactivity and protein-binding behavior.

A novel nonanuclear terbium(III) cluster (9-Tb) supported by salicylaldehyde-condensed phenazinylpyridine bisacylhydrazone was designed, synthesized and fully characterized. Cluster 9-Tb shows excellent structural stability in various solution media. Antibacterial assays demonstrate that 9-Tb exhibits prominent inhibition against Staphylococcus aureus. The antibacterial activity may be attributed to the unique nonanuclear metal skeleton and the metal-organic synergistic effect derived from coordination assembly. In a Staphylococcus aureus-infected full-thickness skin wound model in SD rats, topical administration of 9-Tb remarkably accelerates wound closure. Further histological analyses reveal that 9-Tb facilitates collagen deposition, alleviates excessive inflammatory infiltration and promotes angiogenesis, thereby creating a favorable microenvironment for skin regeneration. In vivo biosafety assessment confirms no obvious organ damage or inflammatory lesions in major tissues of rats. Collectively, the nonanuclear terbium cluster 9-Tb integrates potent anti-Staphylococcus aureus activity, remarkable wound-healing efficacy and excellent biocompatibility, representing a promising candidate for antimicrobial and skin wound repair applications.