Chimia最新文献

Cyclic natural products offer important, unique scaffolds and functionalities for the pharmaceutical industry. They are produced by enzymes catalyzing a wide range of cyclization reactions. This large family of enzymes creates distinctive cyclic structures via a variety of mechanisms naturally evolved for selectivity. In this review, we aim to present an overview of these natural catalysts, the therapeutic compounds for which they are involved in the production, as well as engineering efforts to tune them for anthropogenic needs in human medicine. Biochemical methodologies commonly used for the discovery and engineering of enzymes will also be highlighted, with an emphasis on enzymatic terpene cyclization and Pictet-Spengler-type cyclization.

Fluorescent biosensors are essential for probing analyte dynamics and enzyme activities with high spatial and temporal resolution in living cells by functional microscopy. Recently hybrid, or so called chemigenetic, biosensors have emerged, that integrate the strengths of synthetic fluorophores - such as spectral diversity, high brightness and photostability - with the specificity and sensitivity of genetically encoded sensing units. Beyond enhancing optical performance, synthetic chemistry can also expand the repertoire of sensing units themselves, creating opportunities for novel biosensor designs sensing previously inaccessible analytes. In this review, we summarize the protein-labeling strategies used in chemigenetic biosensor design with particular emphasis on self-labeling protein tags. We further discuss biosensor design principles, representative applications, and emerging advances that highlight the growing impact of chemigenetic biosensors in functional microscopy.

Amino acids are central to biology as signaling molecules and as the building blocks of peptides and proteins, which represent an expanding class of drugs with vast therapeutic potential. The precise modulation of individual residues in therapeutic peptides and proteins is crucial to enhance their pharmacological properties. Expanding beyond the twenty proteinogenic amino acids to include non-canonical amino acids (ncAAs) offers powerful strategies to optimize the stability, selectivity, and potency of peptides. Including ncAAs in the early discovery phase can significantly accelerate lead development and clinical translation. This review examines how diverse platforms integrate ncAAs in early discovery and compares the capabilities and limitations of these discovery technologies. Finally, key challenges are outlined that must be addressed to drive future innovations and explore new therapeutic avenues. Together, these approaches mark a shift towards peptide drug discovery where non-canonical chemistry is not an exception but a necessity.

At the microscale, robotic intelligence cannot rely on circuits or processors; instead, it must emerge directly from responsive materials. Chemistry provides the means: polymers, catalytic and magnetic materials enable single responsive mechanisms such as propulsion and sensing, forming the foundations of physical intelligence. Yet these functions remain limited in isolation. The next step is multiple responsiveness, where combined mechanisms create richer, autonomous behaviours. Conventional monolithic designs often suffer from interference and poor tunability, but modular assembly strategies now offer a solution by integrating discrete functional units without cross-talk. This review traces the progression from single to modular multi-responsive microrobots and highlights how such systems could achieve life-like adaptability for biomedical and environmental applications.

Because the biological activity of a molecule is directly linked to its three-dimensional configuration, the preparation of chiral compounds is a central discipline in synthetic organic chemistry. With the exploitation of photoredox catalysis that gives access to open-shell (radical) intermediates under mild and sustainable conditions, unprecedented molecular architectures can now be synthesized. However, the parent enantioselective transformations have been developed at a slower pace because suppressing non-catalyzed background reactivities has presented a major hurdle. Designer bifunctional photocatalysts containing a H-bonding motif for substrate recognition and a diaryl ketone as the photosensitizer embedded in a chiral scaffold are useful catalysts in asymmetric radical transformations. Herein, an overview of enantioselective transformations in which this class of catalysts has been successful and future directions are discussed.

This perspective discusses the application of multidimensional spectroscopies in the study of electron transfer, proton transfer, and proton-coupled electron transfer (PCET) processes in the excited state. By addressing vibrational modes intimately tied to the reaction coordinate, these techniques aim to probe, perturb, and ultimately steer photochemical reactions. Simultaneously, multidimensional spectroscopies will provide unparalleled insight into these processes, accessing observables not available to conventional ultrafast spectroscopy. Altogether, this approach allows us to move beyond simple observation towards active manipulation of fundamental chemical reactions in the excited state.

Asymmetric hydrogenation (AH) is one of the most important transformations in organic synthesis, enabling efficient access to enantioenriched molecular building blocks used in pharmaceuticals, agrochemicals, and fine chemicals. AH is largely dominated by catalysts based on precious transition-metals. However, concerns over cost, supply, and toxicity have intensified interest in developing metal-free alternatives. Frustrated Lewis pairs (FLPs) - combinations of sterically encumbered Lewis acids and bases - have emerged as a promising metal-free platform for AH, yet they face significant challenges that must be addressed to enable widespread adoption. Our group aims to contribute to this effort by developing new chiral FLP catalysts for AH and exploring FLP-mediated transformations beyond hydrogenation. In this perspective, we summarize the state-of-the-art, outline current challenges, and discuss opportunities to advance the field towards sustainable catalysis.

Enzymes are emerging as a central element of green chemistry due to their high selectivity, biodegradability, and biocompatibility. However, their application in biotechnology is often limited by their poor stability under non-native conditions. Such an instability eventually compromises their catalytic efficiency and economic viability. To date, no single solution exists to universally solve the challenge of enzyme stability. Herein, we summarized the main strategies that have been developed to address this challenge, including enzyme discovery, protein engineering, enzyme immobilization, and computational tools. Beyond stability, this account also highlights recent technologies to improve biocatalytic efficiency. All these approaches are illustrated by examples of our most recent research work. Ultimately, enhancing enzyme stability and activity will have a broad impact for biocatalytic processes in biomedicine, food processing, and chemical manufacturing, among other biotechnology areas.

Radiocarbon dating has long been a cornerstone of archaeological science, offering a reliable method to determine the age of organic materials. Yet when applied to cultural heritage objects, traditional bulk analysis methods often fall short. Our research, supported by an SNSF Ambizione program, seeks to overcome these limitations by shifting the focus from bulk materials to individual molecules. We aim to untangle the mixed carbon sources encountered in heritage materials through compound specific approaches and further target the color of an object, i.e. natural organic dyes and pigments. This perspective opens new avenues for understanding the chronology, provenance, and material history of cultural heritage objects. The implementation of compound specific radiocarbon analysis (CSRA) and compound specific isotopic analysis (CSIA) in heritage science demands not only analytical precision but also an uncompromising approach to exogenous carbon contamination control. Herein, we describe our current efforts in developing color specific carbon isotopic analyses that address this challenge.