Articles

Chemical variational autoencoder (VAE) is a deep learning method for constructing chemical latent spaces, however, the current chemical VAE variants are limited in their ability to handle complex compound structures like natural products. Here, the authors develop a variational autoencoder that can handle natural products and demonstrate its utility as an in silico drug discovery tool.

The bio-hybrid fuel 4,5-dimethyl-1,3-dioxolane can be produced from glucose via 2,3-butanediol (2,3-BDO), however, the separation of microbially produced 2,3-BDO remains costly. Here, the authors develop an alternative process route to 4,5-dimethyl-1,3-dioxolane via the enzymatic production of 2,3-BDO.

Gadolinium-based contrast agents are the gold standard for magnetic resonance imaging (MRI), however, their poor stability causes safety problems in clinical applications. Here, the authors develop two chiral Gd(III) DOTA-based complexes with a macrocyclic backbone that show higher relaxivities and stabilities than benchmark complexes.

Cu(I)-thioether complexes have been widely studied as metalloprotein mimics, but limited structural geometries have been reported to date. Here, the authors demonstrate that a chiral cyclic β-amino acid ligand affords Cu(I)-thioether complexes with chiral conformations and the capacity for hydrogen bonding, offering unusual geometric structures and metal-to-ligand ratios.

Achieving kinetic control over reversible self-assembly processes remains challenging. Here, the authors assemble Rh₄L₄ coordination squares consisting of cis-protected Rh(II) corner sites and linear ditopic ligands under kinetic control, preventing the formation of triangles by modulating the energy landscape with use of a leaving ligand.

Supramolecular networks deposited on surfaces are of interest for a range of applications, but expanding monolayers to well-ordered multilayers remains a significant challenge, not least because analytical tools capable of probing such assemblies are limited. Here, the authors demonstrate that combining AFM-IR with STM enables an assessment of the differences in molecular conformations between 2D and 3D supramolecular networks adsorbed onto a HOPG surface.

Benzil and its derivatives have been widely studied for their luminescence properties, but the effects of ortho- and meta-substituents on photophysical properties have yet to be explored. Here, ortho-, meta- and para-substituted benzil derivatives are accessed via an organocatalytic pinacol coupling of substituted benzaldehydes, and ortho- and meta-substituents are shown to significantly influence the electronic state and luminescence properties of benzil.

The endeavor to harness machine learning to improve antibody-antigen interaction is not only significant but also fraught with challenges due to the limitations of the publicly available datasets. Here, the authors introduce an Antibody Random Forest Classifier that classifies mutations as either deleterious or non-deleterious based on physicochemical features, which enabled the identification of affinity-enhancing mutations in SARS-CoV-2 antibodies with an up to 1000-fold increased binding affinity.

Therapeutic proteins have great potential for the treatment of various diseases, however, achieving high delivery efficiency remains challenging. Here, the authors develop a complex coacervate system formed via the phase separation of anionic metabolite NADPH with a short arginine-rich peptide, and apply it to the redox-responsive drug delivery of therapeutic proteins.

The binding interaction between the Shelterin complex protein TPP1 and the human telomerase enzyme can trigger telomerase maintenance, however, the conformational change of TPP1 functional for binding remains underexplored. Here, the authors characterize the structural properties of a group of amino acids named the TEL-patch within TPP1’s oligosaccharide/oligonucleotide-domain by molecular dynamics simulation, time-series analyses, and graph-based networks, revealing their conformational plasticity and allosteric communication networks.

Copalyl diphosphate synthases (CPSs) catalyze the crucial cyclization step in labdane diterpene biosynthesis to generate stereochemically distinct copalyl diphosphates (CPPs), however, the stereoselectivity within CPSs remains underexplored. Here, the authors report the 3D structure and oligomeric properties of syn-CPS from Oryza sativa, which originally produces syn-CPP but also ent-CPP after mutagenesis.

PUFA-plasmalogens show neuroprotective properties via the stimulation of CREB activation, however, their efficiency is limited by low bioavailabilities. Here, the authors develop PUFA-plasmalogen-loaded liquid crystalline lipid-peptide nanoparticles to achieve sustained CREB activation in an in vitro neurodegeneration model.

Polyurethanes find versatile applications in our daily lives, e.g., as coatings, foams and adhesives, but non-hazardous synthesis routes with renewable feedstocks are urgently needed. Here, the authors report an organocatalytic synthesis route towards non-isocyanate polyurethanes using terpenes as renewable starting materials.

Cathepsin D (CatD) is an aspartic acid protease involved in the immune response of macrophages to bacterial infection, and the development of pH insensitive CatD probes is vital in order to detect its activity across multiple cellular components. Here, the authors develop a water soluble and pH insensitive FRET-based fluorescent probe for the sensitive detection of CatD.

Single-atom catalysts (SACs) are highly promising materials for applications such as electrocatalytic water splitting, but coordination geometries around catalyst centers remain the subject of debate. Here, the authors use spin-polarized ab initio molecular dynamics simulations to compare the aqueous reactivities of iron porphyrin and iron pyridine SACs embedded in graphene, and predict the interfacial water dissociative adsorption mechanism under a moderate electric field for an iron porphyrin SAC.

Modelling the structural transitions of flexible metal-organic frameworks provides key insight into their breathing behaviours, but molecular dynamics simulations performed to date do not typically account for finite size and surface effects affecting the phase transition mechanism. Here, the authors present an approach that allows for the analysis and control of the volume of finite-size structures during molecular dynamics simulations, using a tetrahedral tessellation of nanocrystallite volume.

PAPP-A and PAPP-A2 are two isoforms of pregnancy-associated plasma protein A that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate insulin-like growth factor signaling, however the structure and function of PAPP-A2 remain underexplored. Here, the authors report the cryo-EM structure of PAPP-A2, computational modeling of the PAPP-A2/IGFBP5 complex, and biochemical studies that reveal unique structural features and a lower IGFBP5 cleaving efficiency compared with PAPP-A.

To meet the rising demand for sustainable and simple polymer syntheses, organocatalytic polymerizations are a powerful tool. Here, the authors report the quasi-alternating polymerization of oxirane monomers at room temperature and in solvent-free conditions catalyzed by potassium acetate complexed by 18-crown-6 ether, leading to well-defined polyethers with varied comonomer content and low dispersity values.

Traditional peptide synthesis iteratively elongates the chain from the C-terminus to the N-terminus (C-to-N), however, this process requires excess N-carbamate-protected amino acids and condensation reagents to minimize epimerization. Here, the authors report an alternative N-to-C elongation strategy by catalytic peptide thioacid formation and oxidative peptide bond formation without requiring condensation reagents and excessive protecting group manipulations.

Iron(III) molybdate is a commercial catalyst for selective oxidations such as oxidative dehydrogenation of methanol, but our understanding of the involved (sub)surface and bulk conversion processes remains limited. Here, the authors use modulation excitation IR, operando impedance, and multiwavelength Raman spectroscopy to show the mode of operation of this important catalyst.