Biological Activity of Metal Complexes

Metal complexes play a fundamental role in biological systems and continue to attract sustained interest due to their remarkable potential in therapeutic, diagnostic, and biotechnological applications [1,2,3,4,5,6,7,8]. In recent years, the field of bioinorganic chemistry has advanced rapidly, driven by progress in coordination chemistry, spectroscopy, nanotechnology, and molecular biology [9,10,11,12,13,14,15,16,17,18,19,20,21,22]. These developments have enabled a deeper understanding of how metal ions and complexes interact with biomolecular targets and have opened new avenues for the rational design of metal-based agents for cancer therapy, antimicrobial treatment, imaging, and the study of metal-mediated biochemical processes [23,24,25,26,27,28,29,30].

This Special Issue, “Biological Activity of Metal Complexes”, was conceived to bring together recent developments in the synthesis, characterization, and biological evaluation of metal complexes, with particular emphasis on elucidating their mechanisms of action and biomedical relevance. The contributions collected reflect the inherently multidisciplinary nature of this research area, spanning coordination chemistry, nanomaterials, spectroscopy, computational analysis, and cellular studies.

A notable theme is the development of rhenium(I) tricarbonyl complexes as versatile biologically active platforms. Paparidis et al. report anthrapyrazole-functionalized fac-tricarbonylrhenium complexes that exhibit strong DNA-binding ability, pronounced cytotoxicity toward tumor cells, and promising pharmacokinetic properties, demonstrated through studies with a ^99mTc-analogue, highlighting their dual therapeutic and imaging potential [24].

In a complementary contribution, Carreño et al. present a comprehensive structural, electronic, and biological investigation of a phenanthroline-based rhenium complex [30]. Through the integration of crystallography, electrochemistry, computational studies, and cell viability assays, the authors provide valuable insight into structure–activity relationships and the luminescent behavior of these complexes in biological environments [30].

The interaction of metal complexes with biological macromolecules, particularly DNA and serum proteins, represents another central focus of this Special Issue. The manganese(II) complexes described by Theodoulou et al. demonstrate strong intercalative binding to calf-thymus DNA and reversible association with serum albumins, offering insight into how ligand design influences biomolecular affinity and potential pharmacological behavior [27].

Similarly, Alhashmialameer reports the synthesis of quinolinyl–imine complexes of Cr(III), Mn(II), and Pd(II) via a sonochemical route, followed by biological evaluation and molecular docking studies. These results correlate the coordination structure with antimicrobial, antioxidant, and potential anticancer activities, further emphasizing the importance of ligand architecture in modulating the biological response [28].

Photodynamic therapy and targeted therapeutic strategies are represented by the work of Mantareva et al., who investigate Zn(II)- and Ga(III)-phthalocyanines in combination with the proteolytic enzyme α-chymotrypsin [23]. Their findings demonstrate that enzyme–photosensitizer conjugation can enhance phototherapeutic efficiency while reducing toxicity, illustrating an innovative approach to improving the selectivity of metal-based photosensitizers [23].

The Special Issue also highlights the growing role of inorganic nanomaterials in biological detection and imaging. Phuong et al. describe optimized NaYF₄:Er³⁺/Yb³⁺ upconversion nanocomplexes with controlled morphology and surface functionalization, followed by antibody conjugation for the effective labeling of cancer cells [26]. This work demonstrates how the precise control of nanoparticle structure and surface chemistry translates into improved luminescent performance and bio-recognition capabilities [26].

Beyond therapeutic and imaging applications, understanding the chemical fate of metal-containing compounds in biological environments remains critically important. Degorge et al. investigate the degradation of the organomercurial compound thimerosal by glutathione and cysteine at physiological pH, providing valuable insight into the bioinorganic reactivity of metal species with endogenous thiols and their potential toxicological implications [29].

Collectively, the contributions in this Special Issue demonstrate that the development of biologically active metal complexes requires a balanced integration of synthetic design, physicochemical characterization, and detailed biological evaluation. From DNA binding and protein interactions to photodynamic activity, imaging applications, and toxicological studies, these works highlight the breadth and relevance of research in this rapidly evolving field.

The Guest Editor hopes that this Special Issue will serve as a valuable reference for researchers in bioinorganic and medicinal inorganic chemistry and stimulate further interdisciplinary efforts toward the development of next-generation metal-based diagnostic and therapeutic agents.