Editorial: Chemical biology and coordination chemistry

The application of Coordination Chemistry to research in Chemical Biology has become essential for understanding some biological processes. The importance of metal interactions with biomolecules, enzymes, nucleic acids and lipids is undisputed and can lead to important therapeutic advances. The continuous evolution of coordination chemistry therefore offers potential breakthroughs when addressing complex biological environments and biomedical systems. At the 45th International Conference on Coordination Chemistry (ICCC45) several symposia were held presenting the contributions made by Coordination Chemistry in Chemical Biology and Medical Research. A Special Volume was developed based primarily on contributions from plenary, keynote, invited and contributed speakers, and poster presentations, with a small number of additional contributions that were not part of the conference. These collected works in this Special Volume represent and capture these outputs and their contribution to furthering fundamental coordination chemistry, diagnostics, and the study and treatment of specific diseases, including cancer.

The International Conference on Coordination Chemistry (ICCC) is the longest-running international chemistry conference in the world, with a history dating back to 1950. The 45th International Conference on Coordination Chemistry (ICCC45) was hosted at Colorado State University in Fort Collins from July 28 to 3 August 2024. The conference was returning to the United States of America for the third time in its history and for the first time in 39 years. This successful gathering featured plenary, keynote, and invited speakers from 37 countries across 6 continents, and participants from 44 countries. The ICCC underscores the global importance and reach of all areas of coordination chemistry. The Special Volume is organized into three parts covering key aspects of coordination chemistry including various fundamental aspects of the compounds (Acosta et al., 2026; La Gatta and Pecoraro, 2025; Dinda et al., 2025; Peng, et al., 2024; Ždrnja, et al., 2024; Yoo et al., 2023; Crans and Kostenkova, 2020), the detection and characterization for fundamental biological processes (Gailer, 2026; Al Riyami et al., 2026; Côrte-Real et al.; Crans and Miller, 2025; Mertens et al., 2023; Hu and Wilson, 2022; Nunes et al., 2021) and finally applications of coordination compounds to the study or treatment of diseases (Mulholland et al., 2026; Liu et al., 2026; Boros et al., 2025; Levina et al., 2024; Pham and Chang, 2023; Ariga et al., 2022). Although several papers cover more than one area, we present papers in this special issue representing varies aspects of coordination chemistry and chemical biology. In Part 1 the selected papers address synthesis, structure and X-ray crystallography, fundamental properties of coordination compounds (Acosta et al., 2026; La Gatta and Pecoraro, 2025; Dinda et al., 2025; Peng et al., 2024; Ždrnja et al., 2024; Yoo et al., 2023; Crans and Kostenkova, 2020). In Part 2 the papers highlight the potential application for the detection or characterization of fundamental biological processes (Côrte-Real et al.; Crans and Miller, 2025; Mertens et al., 2023; Hu and Wilson, 2022; Nunes et al., 2021). Contributions in Part 3 are devoted to the development of compounds for the treatment of diseases including cancer and microbial diseases (Mulholland et al., 2026; Liu et al., 2026; Boros et al., 2025; Levina et al., 2024; Pham and Chang, 2023; Ariga et al., 2022). A few papers span across these classifications and they are placed according to the suitability of the topic and their relevance to specific sections.

Part 1. fundamental aspects of coordination compounds and their chemistry

Papers representing the synthesis, structural characterization (protein X-ray crystallography), stability, redox properties and ability to catalyze processes are described in Part 1. This part of the Special Volume highlights the work by Fugarolas et al., Wojtala et al., Merlino, Mordido et al., and Mikata et al.

The paper by Fugarolas et al. discusses the synthesis of Cu(II)-complexes of 4-and 5-nitroimidazole derivatives. The latter are analogs of 2-nitroimidazole derivatives which are used as a front-line treatment against anerobic bacteria, parasites and protozoa. Following the synthesis of the simple 4-and 5-nitroimidazoles, a range of alkyl substituted derivatives were prepared and complexed to CuCl 2 or CuBr 2. Wojtala et al. prepared metal complexes from multifunctional organic ligands containing phosphine-functionalized fluoroquinolones that are derived from two antibiotics (HCp–ciprofloxacin and HNr–norfloxacin). The mononuclear Ru(II) complex is reacted with MnCl 2 to form the heterodimetallic complexes Ru(II)-Mn(II) (Ru(η 6 -p-cymene)Cl 2 PCpMnCl 2 (H 2 O) 2 (RuPCpMn) and Ru(η 6 -p-cymene)Cl 2 PNrMnCl 2 (H 2 O) 2 (RuPNrMn)).

X-ray Crystallography is a key method for determining solid-state structures. The contribution by Antonello Merlino concerns the determination of protein structures using X-ray diffraction techniques. The majority of the protein crystal structures in the Protein Data Bank (wwPDB consortium, 2019; Protein Data Bank 2019) have been determined at 100 K by collecting X-ray diffraction data while holding crystals under a liquid nitrogen flux. A growing awareness that low-temperature diffraction data collection is accompanied by some differences from the structures elucidated at functional temperatures is prompting crystallographers to collect X-ray diffraction data at elevated temperatures such as ambient temperature or at body temperature (37 °C/310 K).

Chemical Stability and Redox properties are critical parameters for metal complexes and biological systems. In the contribution by Mordido et al. a class I c -type cytochrome from Wolinella succinogenes that shows a mixture of high/low spin state populations in its visible absorption spectrum is studied. A structural model of Cytochrome c 552 from Wolinella succinogenes suggests that the heme is methionine/histidine(Met/His)-coordinated and highly solvent-exposed. The UV-visible absorption spectra obtained at different pH values reveal the presence of a protonatable group with a pKa of 7.3. The pH was also found to influence the reduction potential of the cytochrome c 552 (E m 0’ of 97 ± 5 mV, pH 7.0). These studies document how subtle structural changes can affect function. Mikata et al. investigate the coordination chemistry of pentadentate ligands and their relevance to redox-active copper metalloenzymes. The weak metal-coordinating abilities of the anilinic nitrogen combined with the rigid o-phenylenediamine skeleton constitute a unique pyridine and quinoline binding site in proteins. Non-coordinating alkyl groups (CH 3 or CH 2 Ph) in the ligands cause significant differences in the coordination geometries of the resulting Cu(II) complexes and their catalytic properties. Specifically, the aerobic alcohol oxidation reactions were measured in the presence of CuBr and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), with N -benzyl- N,N′,N′ -tris(2-quinolylmethyl)-1,2-phenylenediamine (Bn-TQPHEN, L4), or N -methyl- N,N′,N′ -tris(2-pyridylmethyl)-1,2-phenylenediamine (Me-TPPHEN,L1). The latter demonstrated a higher oxidation rate consistent with the lower electron density of the methyl group.

Part 2. potential application for the detection or characterization of fundamental biological processes

Part 2 contains contributions describing coordination compounds and their potential application for the detection and/or characterization of fundamental biological processes. This part of the volume contains papers that present metallacrowns as a platform for measuring lanthanide luminescence, the use of technetium-99m (99m Tc) radiopharmaceuticals, the monitoring of DNA damage, the delivery of undruggable material in hollow enzymes, a class of antioxidants causing DNA damage, investigations of metal ion-effects on mitochondria, and iron uptake in humans. It includes contributions from Naseri and Pecoraro, Ma et al., Gaertner et al., Lucignano and Ferraro, Dolan et al. and Sawai.

Metallacrowns (MCs) are an inorganic class of coordination compounds that are counterparts to the organic crown ethers, and they form the topic of a minireview by Naseri and Pecoraro. In MCs the characteristic C-atoms in the C-O repeating units of crown ethers are replaced by repeating -M-N-O- units, where M is a metal. MCs offer remarkable structural diversity, as the ring size, type of metal and oxidation number can be varied and giving rise to a great variety of cation binding sites within the central cavity. The minireview describes metallacrowns bearing gallium(III) as the ring metal and highlights the intriguing photophysical properties and potential applications of Ga(III)-Ln(III) MCs as a platform for accessing lanthanide luminescence.

Advances in healthcare outcomes depend not only on new therapeutic drugs but on advancing new diagnostic imaging techniques through intelligent pragmatic approaches. In her monograph, Ma et al. describes the widespread use of technetium-99m (99m Tc) as a radiopharmaceutical and explores how new developments in the field have been effective in using chelator (mercaptoacetyl-triglycine, hexamethylpropylene amine oxine, and 2-hydrazinonicotinamide) and ligand (organometallic and phosphine) motifs to generate 99m Tc-labelled radiopharmaceuticals that can simultaneously act as biomolecular pharmacophores. Such advances enable the clinician and patient to benefit from receptor-targeted molecular imaging using existing nuclear medicine infrastructures, supply chains, γ-scintigraphy and Single-Photon Emission Computed Tomography (SPECT) cameras. Given their similar biodistribution patterns, innovations in 99m Tc and 188 Re chelator chemistry point to the development of 99m Tc and 188 Re receptor-targeted theranostic systems in the future.

Gaertner et al. introduce an in vitro, gel-electrophoresis, DNA-damage assay that evaluates the antioxidant ability of a series of hydrophobic compounds (polyphenols, bipyridine, and selone as well as the radical scavenger edaravone) in a quantitative manner. Their assay, using copper and iron complexes in high ethanol concentrations, provides an approach to measure and to compare metal-mediated antioxidant behaviors of this type of hydrophobic antioxidant. The assay allowed the authors to shed insight into whether metal-coordination is involved in the mechanisms of action of copper or iron systems and to test known and new drugs that cross the blood-brain barrier for the treatment of Alzheimer’s, Parkinson’s, and other diseases caused by oxidative stress. Importantly the article determines that the glutathione peroxidase mimic ebselen (IC 50 around 280–450 µM) and a group of ebselen derivatives can prevent copper-mediated DNA damage but do not inhibit iron-mediated DNA damage.

Although metal-coordination can greatly enhance the efficacy of known drugs, providing structural options and the potential for their targeted release, metal-coordination can present new challenges around aqueous solubility, chemical stability and selectivity. In their mini-review, Lucignano and Ferraro discuss the use of ferritin (Fn), a protein with a hollow cage structure as a nanocarrier. Over the past decade, different nanodrug delivery systems based on Fn have been reported. Multiple studies have confirmed that Fn nanocarriers can enhance the bioavailability of insoluble drugs, promote tumor-specific accumulation and reduce the drug toxicity toward healthy tissues. Examples of successful ferritin-based nanoconjugates include delivery of Pt(IV) prodrugs, improved CO release from a Ru-based CO releasing molecule, and delivery of Au(III) complexes/nanoclusters with both Auranofin and Aurothiomalate (AuTM). The review discusses the validity of the approach of using hollow proteins to carry a load and underlines the need to develop chemically - and genetically-modified subtypes of ferritin for effective drug deliveries.

Dolan et al. investigated mitochondrial function and the effects of two biologically redox active first row transition metals, manganese and vanadium. Both metal ions have been associated with protective and deleterious effects (Aureliano et al., 2023). The vanadium and manganese salts (V IV OSO 4, NaV V O 3, Mn II Cl 2) and acetoacetate (Hacac) complexes (V IV O(acac) 2 and Mn II (acac) 2) decreased murine cardiac mitochondrial respiration in a concentration dependent manner, and the effect was attenuated when the metals were complexed to an acac - ligand. In contrast, only V IV OSO 4 and V IV O(acac) 2 induced significant mitochondrial swelling, with greater sensitivity over NaV V O 3, Mn II Cl 2, Mn II (acac) 2 and free Hacac ligand. These studies demonstrate distinct effects by vanadium and manganese ions on cardiac mitochondrial function which varies with the metal ion, metal oxidation state and metal ion speciation.

In the human body, iron is associated with various proteins that regulate vital functions, such as DNA synthesis, oxygen transport and storage, and energy production. Insufficient iron impairs cell activity, whereas excess iron, particularly in its ferrous (Fe(II)) form, can generate harmful reactive oxygen species through the Fenton reaction. Consequently, the human body tightly controls the oxidation state and distribution of iron using specialized proteins and this topic was reviewed by Sawai. Under physiological conditions, iron mainly exists as ferric (Fe(III)-species) compounds like Fe(OH) 3, which is poorly soluble and therefore often chelated to biomolecules that similarly have low solubility. To overcome this solubility problem, living systems have evolved mechanisms to reduce the less soluble Fe 3+ -species to the more soluble Fe 2+ -species. The Fe 2+ -ion can then bind to heme-containing enzymes of the transmembrane cytochrome b family and is transported across cell membranes while also undergoing processing by metalloreductases. This review by Hitomi Sawai describes the two proteins classes of enzymes leading to iron uptake in humans one being the heme-containing cytochrome b family and the other a group of highly conserved metalloreductases belonging to the STEAP family of proteins that facilitate the reduction of Fe(III) to Fe(II) in the process.

Part 3. applications of coordination complexes in chemical biology to study or potentially treat diseases highlighting cancer

The application of metal complexes to the treatment and understanding of disease is a large focus of research. Cancer remains one of the world’s leading causes of mortality, with around 10 million deaths and over 19 million new cases recorded annually, according to GLOBOCAN 2022 (Global Cancer Statistics, 2022). There is clearly a need to find more effective, selective and alternative treatments, and novel approaches to tackling this disease are gaining traction (Crans and Miller, 2025). The need for non-traditional methods includes metal-containing small molecules, biologicals in phototherapeutics and in new biologicals and approaches such as phototherapeutics, an area where the properties of metal-containing compounds excel (Al Riyami et al., 2026). In Part 3 we present a collection of contributions largely focusing on cancer, but also including contributions that target microbial diseases as well as compounds with a broad spectrum of activities with potential for the treatment of other diseases. Specifically, the articles presented by Côrte-Real et al., Zaballa et al., Banti et al., Condon et al. and Talgatov et al. demonstrate how the effectiveness of their complexes might be optimized toward specific cancers, under tumor specific conditions (physiological pH, hypoxia against drug resistant cell lines) and ultimately offer new therapeutic advances.

In their mini-review, Côrte-Real et al. describe the anticancer potential of a series of metal complexes (Zn(II), Cu(II), V(IV)O, Ni(II), Fe(III) and Ru(II) metal centers) that contain functionalized derivatives of 8-hydroxyquinoline (8-HQ). The review captures insights seeking to exploit the additive or synergistic effect of metal coordination (di-, tri- or in rare cases, tetra-dentate coordination) of derivatives of this versatile ligand. In particular, the potential of 8-HQ systems with imine substituents at the 2 position are investigated. The variant families of compounds are Schiff bases (-C=NR), hydrazones (-C=N-NHR) and hydrazide-hydrazones (-C=N-NH-C(R) = 0). In vivo tests of the Cu(II) complexes against A549 cells (human lung cancer) demonstrate IC 50 values lower than those of cisplatin or 5-fluorouracil. Correia and co-workers discuss the challenges in establishing structure/property relationships between and within this diverse series of complexes. Trends are identified, e.g., the increased cytotoxicity of some ligand systems on the introduction of electronegative elements such as fluorine, the low aqueous solubilities, and varying selectivity. Solutions to some of these challenges are provided.

The research reported by Zaballa et al. describes a comparative study of Cu(II) and Zn(II) complexes involving a bifunctional ligand (ISAMBZ) that contains both oxindole and benzamide moieties. The potential suitability of a series of known and new complexes for chemotherapeutic applications is assessed by multiple techniques. Specifically, spectroscopic studies of ligand binding to DNA, lipid peroxidation, and cell viability assays are presented. The evaluation of reactive oxygen species (ROS) generation, cytotoxicity toward malignant cells (cervical HeLa and melanoma SK-Mel) are compared to similar studies in non-tumor cells (fibroblasts). The best performing molecules demonstrate IC 50 values in μM ranges.

Prevention is an alternative and very desirable pharmacological approach to cancer, and is illustrated in the contribution by Banti et al. Conceptually building on the photoprotective light-scattering properties of ZnO nanoparticles and the preventative skin penetration effects of carboxymethylcellulose (CMC) hydrogels, these authors explore the opportunities provided from the doping of CMC hydrogels with the water-soluble Zn(II) aspirinato complex (ZnAsp). Their materials were spectroscopically and structurally characterized and found to be photochemically robust. They measure the in vitro cytotoxicity of CMC@ZnAsp and ZnAsp against immortalized human keratinocyte (HaCaT) cells. These studies show that the former is effective at promoting healing through the growth and migration of new epithelial cells. They also establish that the material has desirable in vivo anti-inflammatory activity, low cytotoxicity and Ultraviolet Protection Factor (UPF), which in combination indicate the system’s potential for skin-protection.

Within the field of phototherapeutics, Condon et al. and Talgatov et al., are seeking to identify systematic changes in the molecular structure and to illicit useful design protocols (Al Riyami et al., 2026). These contributions include in-depth studies on the applications of known systems. In their communication, Condon et al. further consider two known 2,2′bipyridine complexes that comprise different ethynyl-extended Nile Red chromophores and look more closely at the solvent and counter-ion dependences of their photophysics. As with the conjugated McFarland systems discussed below, the excited state is dominated in both molecules by a non-emissive but sustained triplet intraligand charge-transfer (3 ILCT) state which, in the more linear 3-ENR molecule, extends across the entirety of the Nile Red-bipy ligand. Experimental and computational analyses indicate that it is this state that is responsible for the phototoxicity observed against a human breast cancer (SKBR) cell line, however both molecules are co-localized within the cell plasma and cytotoxic in the dark at 50 nM concentrations.

Talgatov et al. systematically investigate four Ru(II) polypridyl complexes (Ru(6,6′-dmb) 2 (IP- n T) where IP- n T is an oligothiophene-extended imidazo[4,5- f ][1,10]phenanthroline ligand and n = 0–4). They present an experimental, spectroscopic and computational evaluation to establish how ligand chain length and co-ligand environments control the topology of the excited-state reactivity and the phototherapeutic activity. They demonstrate that increasing oligothiophene length progressively stabilizes triplet intraligand charge-transfer (3 ILCT) excited states at the expense of photodissociative metal-centered (3 MC) pathways. The observed photocytoxicity of the Ru- 3 T/ 4 T complexes when tested on a mammalian SK-MEL-28 human melanoma cell line show the lead compound Ru- 4 T achieving low-nanomolar photocytotoxicity and phototherapeutic indices exceeding 3,800 under both normoxic and hypoxic conditions. The authors explore whether their established excited-state design protocols translate to the light-assisted antibacterial properties of the series. Ru- 4 T is the only complex to display strong light-selective activity and only in the less stress-tolerant Gram-negative bacterium, S. aureus. However, the fact that some selectively was obtained is very important for future compound design and reinforces the importance of the biological context.

Antimicrobial resistance (AMR) is cited among the top ten threats to global public health by the World Health Organization (World Health Organization, 2023; Vitali et al., 2025). We, therefore, have contributions to the development of antimicrobial drugs and these are described by Fugarolas et al. and by Wojtala et al.. Understanding the processes involved in antibacterial activity is described in the review of Fugarolas et al., which incorporates original data and discusses the influence of positional substitution on the well-established antibacterial and antiparasitic properties of the pro-drugs, 2, 4, and 5-nitroimidazoles. The review provides an overview of these ligand systems as well as the Cu(II), Ag(I) and Cd(II) complexes. The contribution by Wojtala et al. shows that complexation of a second metal has no effect on the antibacterial behavior of antibiotic-inspired phosphinofluoroquinolone ligand backbones (derived from ciprofloxacin PCp and norfloxacin PNr). The phosphine functionalization does not inhibit the in vitro antimicrobial activity of the fluoroquinolone against Gram-negative Klebsiella pneumoniae. The importance of testing the activity of ligands themselves is emphasized as the metallo-compounds do not out-perform the ligand in terms of antibacterial response.

The final contribution by Rosete-Luna et al. is covering the broad spectrum activities of curcumin (a bis-α,β-unsaturated β-diketone and an active component of turmeric rhizome) and the complexes formed with various metals. Coordination of curcumin to 4d/5d metals helps to overcome its low solubility, hydrophobicity and oral bioavailability, as well as its chemical instability and high rate of metabolism. Curcumin metal complexes have been studied for their antibacterial, anticancer and antifungal activities and in addition to several other lines of enquiry. Highlighted activities relate to the ability of some metal complexes to detect and stain β-amyloid plaques (Re(I), Ir(III)), bind to DNA, to possess significant antioxidant and antimicrobial capacity, as well as demonstrating micromolar cytotoxicity (Ru(II), Pt(II)). These activities, and the interest in designing metal complexes that contain natural products, show a promising future for these classes of compounds.