【明日直播】第14届 Angewandte Advances 前沿交叉论坛震撼发布！

Small molecule activation constitutes one of the main frontiers of inorganic and organometallic chemistry, with much effort directed towards the development of new processes for the selective and sustainable transformation of abundant small molecules such as dioxygen (O2), water (H2O), hydrogen peroxide (H2O2) or protons (H+) into high-value chemical feedstocks and energy resources. Because nature mostly uses metal ions to activate these relatively inert molecules and modulate their reactivity, much inspiration for the field has come from bioinorganic chemistry. This talk will focus on some of the recent highlights from our group on homogenously catalyzed bioinspired activation of small molecules, as well as stoichiometric reactions that further our understanding towards such ends. It will cover many aspects of small molecule activation including: organometallic chemistry, spectroscopy, synthesis, and detailed mechanistic studies involving trapping of reactive intermediates. The demonstrated examples will help to emphasize the continuous effort of our group in uncovering the structure-reactivity relationships of biomimetic model complexes, which may allow vital insights into the prerequisites necessary for the design of efficient catalysts for the selective functionalization of unactivated C–H bonds, O2/H2O/H2O2 activations, or H+ reductions by using cheap and readily available first-row transition metals under ambient conditions.

DNA aptamers refer to nucleic acid species that have been engineered through systematic evolution of ligands by exponential enrichment (SELEX) to bind to various molecular targets. The nanostructure of DNA aptamers can be easily transformed through hybridizing with complementary strands, and the aptamers can realize reproducible transformation of its nanostructure at a high temperature and high salt concentration. These features make DNA aptamers a powerful tool in the field of chemical and biological analysis. However, the limited chemical functionality of nucleobases can lead to the paucity of nanostructures and functions in a natural nucleic acid library. The chemical capability to synthesize artificial nucleotides can expand the chemical space of nucleic acid libraries and further increase the functional diversity of nucleic acids. In view of this situation, we developed an artificial-nucleotide-expanded cell SELEX method for modular expansion of the chemical space of nucleic acid libraries. Using this strategy, we have discovered a series of functional nucleic acid aptamers those can regulate the protein-protein interaction of target proteins and can be used in drug design. This chemical design assisted in vitro selection approach enable the generation of a new class of functional nucleic acids for elucidating the molecular basis of biological activities and uncovering new design of protein-inhibitor pharmaceuticals.

Even though the role of microbiome in cancer has only recently been discovered, it is evident that microbiome research holds a great promise for cancer treatment. While the immediate impact may be limited by the complexities of translating in vitro findings to clinical applications, the long-term implications suggest the potential for tailored microbiome-based therapies, thereby introducing more accurate and efficient strategies for individuals with cancer. In this presentation, we for the first time will demonstrate that despite the multifactorial nature of the microbiome, manipulating its composition can serve as a viable therapeutic avenue for drug development through screening and design strategies.

In recent years, metal-based nanoparticles based on metalloimmunology have attracted tremendous attentions in biomedical fields due to their excellent efficacy. Variety of metallic nanomaterials and different metal oxide/sulfide/nitride nanostructures can help realize targeted delivery of the metal ions and the synergistic theranostics. The activation of the stimulator of interferon gene (STING) pathway is considered as the most potent approach for reprogramming the immunosuppressive tumour-associated myeloid cells within the TME, inducing an antitumour adaptive immune response and increasing the immunogenicity of tumours. Various types of STING agonists, such as modified cyclic dinucleotides, polymers, synthetic small-molecule agonists and metal ions (Mn2+ and Zn2+), have been reported to efficiently activate STING. Recent studies have shown that Mn2+ ions have emerged as a STING agonist with clinical potential. The dynamics of intracellular release or exchange of metal ions from nanomaterials following their cellular internalization are also discussed. This talk also highlight the powerful performance of nanoadjuvants in vaccine development against virus infection.

Over the past few decades, research on the chemistry of gold has progressed rapidly, encompassing topics like catalysis, supramolecular chemistry, molecular recognition, etc. These chemical properties are of great value in developing therapeutics or orthogonal catalysts in biology. However, the presence of concentrated nucleophiles and reductants, particularly thiol-containing serum albumin in blood and glutathione (GSH) inside cells that can strongly bind and quench the active gold species, makes it difficult to translate the chemistry of gold from test tubes into living systems. In this regard, modulating the chemical reactivity of gold complexes to conquer nonspecific interactions with thiols and meanwhile to controllably activate their reactivity in a spatiotemporal manner is of pivotal importance to develop gold complexes for biomedical applications. In this talk, the concept of developing stimuli-activatable gold complexes will be highlighted, with several recently developed examples. These complexes display masked chemical properties, the bioactivity of which can be spatiotemporally activated at the target site by leveraging approaches from classic structure design to recently emerged photo- and bioorthogonal-activation. (References: Acc. Chem. Res. 2023, 56, 1043-1056; J. Am. Chem. Soc. 2024, 146, 8547-8556)