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Partial to Total Generation of 3D Transition-Metal Complexes. Journal of chemical theory and computation The design of transition-metal complexes (TMCs) has drawn much attention over the years because of their important applications as metallodrugs and functional materials. In this work, we present an extension of our recently reported approach, LigandDiff [Jin et al. , 4377(2024)]. The new model, which we call multi-LigandDiff, is more flexible and greatly outperforms its predecessor. This scaffold-based diffusion model allows de novo ligand design with either existing ligands or without any ligand. Moreover, it allows users to predefine the denticity of the generated ligand. Our results indicate that multi-LigandDiff can generate well-defined ligands and is transferable to multiple transition metals and coordination geometries. In terms of its application, multi-LigandDiff successfully designed 338 Fe(II) spin-crossover (SCO) complexes from only 47 experimentally validated SCO complexes. And these generated complexes are configurationally diverse and structurally reasonable. Overall, the results show that multi-LigandDiff is an ideal tool to design novel TMCs from scratch. 10.1021/acs.jctc.4c00775
High-Throughput Combinatorial Metal Complex Synthesis. Angewandte Chemie (International ed. in English) High-throughput combinatorial metal complex synthesis has emerged as a powerful tool for rapidly generating and screening diverse libraries of metal complexes, enabling accelerated discovery in fields such as catalysis, medicinal chemistry, and materials science. By systematically combining building blocks under mild and efficient conditions, researchers can explore broad chemical spaces, increasing the likelihood of identifying complexes with desired properties. This method streamlines hit identification and optimisation, especially when integrated with high-throughput screening and data-driven approaches like machine learning. Despite challenges such as scalability and purity control, recent advancements in automation and predictive modelling are enhancing the efficiency of combinatorial synthesis, opening new avenues for the development of metal-based catalysts, therapeutic agents, and functional materials. 10.1002/anie.202420204
Recent Advances of Metal Complexes in the Treatment of Hepatocellular Carcinoma. Journal of medicinal chemistry Chemotherapy has long been used in the clinical management of hepatocellular carcinoma (HCC), driving the development of anticancer chemotherapy drugs. Platinum complexes have attracted significant attention and have led to the creation of a series of platinum-based drugs used in diverse cancer treatments, including HCC. However, the clinical use of platinum drugs faces critical challenges due to drug resistance and side effects. Consequently, ongoing efforts have been devoted to the continuous development of new metal complexes with antitumor properties, aiming to serve as effective alternatives for HCC treatment. In this Perspective, we summarize and highlight the progress and relevant mechanisms related to new metal complexes in the treatment of HCC over the past decade. The development of metal complexes has the potential to further expand the scope of chemotherapy applications for HCC. 10.1021/acs.jmedchem.4c01850
Channel-assembling tumor microenvironment on-chip for evaluating anticancer drug efficacy. Journal of controlled release : official journal of the Controlled Release Society Organ-on-a-chip is an advanced system for evaluating drug response in diseases. It simulates the in vivo tumor microenvironment, aiding in the understanding of drug mechanisms and tumor responses. It mimics the structure of the tumor microenvironment and the dynamic conditions within the body. As a result, it holds the potential for applications in precision and personalized medicine. However, there are still limitations in sequential development processes and complex structures, resulting in time-consuming molecular interference during system development. In this study, we developed a channel-assembling tumor microenvironment-on-chip (CATOC) system to overcome these limitations. CATOC was easily segmented into blood vessels and a tumor microenvironment-on-chip, which can be independently developed. The tumor microenvironment-on-chip consists of two independent channels for evaluating drug responses in different types of tumor microenvironments. Each fully developed system was physically interconnected to create a CATOC. Interconnected CATOC was used to validate chemical and targeted anticancer drug responses in different subtypes of the breast tumor microenvironment. We also emphasized the significance of on-chip experiments by observing the drug response of tumor spheroids on CATOC and scaffold-free platforms. 10.1016/j.jconrel.2024.11.030
Self-Assembled Metal Complexes in Biomedical Research. Advanced materials (Deerfield Beach, Fla.) Cisplatin is widely used in clinical cancer treatment; however, its application is often hindered by severe side effects, particularly inherent or acquired resistance of target cells. To address these challenges, an effective strategy is to modify the metal core of the complex and introduce alternative coordination modes or valence states, leading to the development of a series of metal complexes, such as platinum (IV) prodrugs and cyclometalated complexes. Recent advances in nanotechnology have facilitated the development of multifunctional nanomaterials that can selectively deliver drugs to tumor cells, thereby overcoming the pharmacological limitations of metal-based drugs. This review first explores the self-assembly of metal complexes into spherical, linear, and irregular nanoparticles in the context of biomedical applications. The mechanisms underlying the self-assembly of metal complexes into nanoparticles are subsequently analyzed, followed by a discussion of their applications in biomedical fields, including detection, imaging, and antitumor research. 10.1002/adma.202416122
Tailored Metal-Based Catalysts: A New Platform for Targeted Anticancer Therapies. Journal of medicinal chemistry Innovative strategies for targeted anticancer therapies have gained significant momentum, with metal complexes emerging as tunable catalysts for more effective and safer treatments. Rational design and engineering of metal complexes enable the development of tailored molecular structures optimized for precision oncology. The strategic incorporation of metal complex catalysts within combinatorial therapies amplifies their anticancer properties. This perspective highlights the advancements in synthetic strategies and rational design since 2019, showing how tailored metal catalysts are optimized by designing structures to release or synthesize active drugs, leveraging the target-specific characteristics to develop more precise cancer therapies. This review explores metal-based catalysts, including those conjugated with biomolecules, nanostructures, and metal-organic frameworks (MOFs), highlighting their catalytic activity in biological environments and their / performance. To sum up, the potential of metal complexes as catalysts to reshape the landscape of anticancer therapies and foster novel avenues for therapeutic advancement is emphasized. 10.1021/acs.jmedchem.4c01680