Chemical Reviews最新文献

The electron density determines all properties of a system of nuclei and electrons. It is both computable and observable. Its topology allows gaining insight into the mechanisms of bonding and other phenomena in a way that is complementary to and beyond that available from the molecular orbital picture and the formal oxidation state (FOS) formalism. The ability to derive mechanistic insight from electron density is also important with methods where orbitals are not available, such as orbital-free density functional theory (OF-DFT). While density topology-based analyses such as QTAIM (quantum theory of atoms-in-molecules) have been widely used, novel, vector-based techniques recently emerged such as next-generation (NG) QTAIM. Density-dependent quantities are also actively used in machine learning (ML)-based methods, in particular, for ML DFT functional development, including machine-learnt kinetic energy functionals. We review QTAIM and its recent extensions such as NG-QTAIM and localization-delocalization matrices (LDM) and their uses in the analysis of bonding, conformations, mechanisms of redox reactions excitations, as well as ultrafast phenomena. We review recent research showing that direct density analysis can circumvent certain pitfalls of the FOS formalism, in particular in the description of anionic redox, and of the widely used (spherically) projected density of states analysis. We discuss uses of density-based quantities for the construction of DFT functionals and prospects of applications of analyses of density topology to get mechanistic insight with OF-DFT and recently developed time-dependent OF-DFT.

The development of potent, specific, and pharmacologically viable chemical probes and therapeutics is a central focus of chemical biology and therapeutic development. However, a significant portion of predicted disease-causal proteins have proven resistant to targeting by traditional small molecule and biologic modalities. Many of these so-called “undruggable” targets feature extended, dynamic protein–protein and protein–nucleic acid interfaces that are central to their roles in normal and diseased signaling pathways. Here, we discuss the development of synthetically stabilized peptide and protein mimetics as an ever-expanding and powerful region of chemical space to tackle undruggable targets. These molecules aim to combine the synthetic tunability and pharmacologic properties typically associated with small molecules with the binding footprints, affinities and specificities of biologics. In this review, we discuss the historical and emerging platforms and approaches to design, screen, select and optimize synthetic “designer” peptidomimetics and synthetic biologics. We examine the inspiration and design of different classes of designer peptidomimetics: (i) macrocyclic peptides, (ii) side chain stabilized peptides, (iii) non-natural peptidomimetics, and (iv) synthetic proteomimetics, and notable examples of their application to challenging biomolecules. Finally, we summarize key learnings and remaining challenges for these molecules to become useful chemical probes and therapeutics for historically undruggable targets.

Noncanonical amino acids (ncAAs) are synthetic building blocks that, when incorporated into proteins, confer novel functions and enable precise control over biological processes. These small yet powerful tools offer unprecedented opportunities to investigate and manipulate various complex life forms. In particular, ncAA incorporation technology has garnered significant attention in the study of animals and their constituent cells, which serve as invaluable model organisms for gaining insights into human physiology, genetics, and diseases. This review will provide a comprehensive discussion on the applications of ncAA incorporation technology in animals and animal cells, covering past achievements, current developments, and future perspectives.

Anthropogenic activities related to population growth, economic development, technological advances, and changes in lifestyle and climate patterns result in a continuous increase in energy consumption. At the same time, the rare metal elements frequently deployed as catalysts in energy related processes are not only costly in view of their low natural abundance, but their availability is often further limited due to geopolitical reasons. Thus, electrochemical energy storage and conversion with earth-abundant metals, mainly in the form of single-atom catalysts (SACs), are highly relevant and timely technologies. In this review the application of earth-abundant SACs in electrochemical energy storage and electrocatalytic conversion of chemicals to fuels or products with high energy content is discussed. The oxygen reduction reaction is also appraised, which is primarily harnessed in fuel cell technologies and metal-air batteries. The coordination, active sites, and mechanistic aspects of transition metal SACs are analyzed for two-electron and four-electron reaction pathways. Further, the electrochemical water splitting with SACs toward green hydrogen fuel is discussed in terms of not only hydrogen evolution reaction but also oxygen evolution reaction. Similarly, the production of ammonia as a clean fuel via electrocatalytic nitrogen reduction reaction is portrayed, highlighting the potential of earth-abundant single metal species.

Cellular function is controlled through intricate networks of signals, which lead to the myriad pathways governing cell fate. Fluorescent biosensors have enabled the study of these signaling pathways in living systems across temporal and spatial scales. Over the years there has been an explosion in the number of fluorescent biosensors, as they have become available for numerous targets, utilized across spectral space, and suited for various imaging techniques. To guide users through this extensive biosensor landscape, we discuss critical aspects of fluorescent proteins for consideration in biosensor development, smart tagging strategies, and the historical and recent biosensors of various types, grouped by target, and with a focus on the design and recent applications of these sensors in living systems.