Articles

Fragment-based drug design is an effective approach to identifying potential binders for a given target protein, but accurately capturing changes in affinity associated with a given set of chemical modifications remains challenging. Here, the authors evaluate the use of absolute binding free energy calculations in guiding fragment optimisation decisions, finding that such calculations can usefully guide fragment elaborations to maximise affinity.

Bottom-up nanomaterial fabrication enables control over nano building-block structure and structure-property relationships, affording opportunities to engineer devices and materials with desirable electronic and optoelectronic behaviors. Here, the authors produce stable oligophenylene dithiol cross-linked gold nanoparticle nanosheets via interfacial self-assembly and show the emergent effects of the cross-linkers on the material’s electronic, optical and photoconducting properties.

Enhancing the hydrophilicity of hydrophobic molecular scaffolds allows to increase their aqueous solubility and therefore their usability for a range of applications. Here, N/O heteroatom doping of polycyclic aromatic hydrocarbons is shown to switch the skeleton from hydrophobic to hydrophilic, enhancing aqueous solubility and facilitating self-assembly in water.

Time-resolved single-crystal X-ray diffraction experiments largely focus on timescales shorter than microseconds, whereby slower population dynamics are missed. Here, the authors resolve the 3D structures of photoexcited solid-state species with millisecond-to-minute lifetimes using pump-multiprobe SCXRD.

Cyclodipeptide synthases (CDPSs) generate a wide range of cyclic dipeptides using aminoacylated tRNAs as substrates, however the substrate selection mechanism is not yet known. Here, the authors investigate the substrate promiscuity of two histidine-incorporating CDPSs to generate an extensive library of products which complement the chemical realm of histidine-containing cyclic dipeptides.

Pemigatinib is an FDA-approved drug for the treatment of cholangiocarcinoma, but while it is known to target fibroblast growth factor receptors, its mechanism of action is still not fully understood. Here, biochemical and structural analyses reveal that pemigatinib is a potent and selective FGFR1–3 inhibitor, and has excellent potency against the Val-to-Ile gatekeeper mutation.

Understanding the roles of oxygen species at reducible metal oxide surfaces is key to improving catalyst performance. Here, a combination of operando diffuse reflectance infrared Fourier transform spectroscopy and mass spectrometry are employed to explore the behaviours of oxygen species during H₂ oxidation at β-MnO₂ surfaces.

Biosourced and biodegradable organic electrode materials are investigated for environmentally benign energy storage, but their performance at higher current density is often poor. Here, the authors construct electrodes with quinone-based species from Sepia melanin and tannins on treated carbon paper and observe electrode capacitance as high as 1355 mF cm⁻² at current densities up to 10 A g⁻¹.

The installation of difluoromethylene groups into bio-relevant molecules allows access to important scaffolds, but existing methods to do so often rely on oxidative chemical species that can hamper reactivity. Here, radical hydrodifluoromethylation with a wide range of unsaturated C–C bonds is achieved via an electroreductive two-pronged approach, granting access to a variety of difluoromethylated organic molecules.

Piezoelectric fields can be exploited in photocatalysis to decrease the rate of photogenerated electron and hole recombination. Here, the authors demonstrate that a BaTiO₃/WS₂ composite is a highly effective piezo-photocatalyst for the degradation of water pollutant ofloxacin.

Efficient electron-hole separation and carrier utilization are key factors in photosynthetic systems. Here, the authors achieve efficient charge separation following a photogenerated hole-transfer band-trap pathway in the ternary composite Pt@NH₂-UiO-66/CdS, resulting in photocatalytic hydrogen evolution with good stability and a quantum efficiency of 40.3% at 400 nm irradiation.

Photoinduced conjugation has been broadly used for functionalization of molecules but is limited by possible photodegradation. Here, the authors report a robust amide bond formation method based on the photoreaction of 3-acylindolizines with amines triggered via red-light irradiation in nearly quantitative yields within less than 5 min.

Photo-mediated radical dearomatization involving 5-exo-trig cyclizations has proven to be an important route to accessing spirocyclic compounds, whereas 6-exo-trig spirocyclization has been much less explored. Here, a dearomative annulation cascade is realized through a photoredox-mediated C–O bond activation of aromatic carboxylic acids to produce two kinds of spirocyclic frameworks, whereby the spirocyclizations are triggered by acyl radical formation from benzoic acids leading to spiro-chromanones via a direct intramolecular 6-exo-trig cyclization or spirocyclic lactams via an intermolecular addition/5-exo-trig cyclization cascade.

In situ illumination of liquid-state NMR samples allows to characterise light-dependent chemical and biological phenomena, but, in practice, the position of an NMR sample deep within the bore of a spectrometer magnet renders such illumination challenging. Here, the authors demonstrate the working principles of a sample illumination device, with an LED array positioned directly at the top of special sample tube, which is inserted into the NMR spectrometer.

Methoxy polyethylene glycol (mPEG) is widely attached to drug molecules to improve their therapeutic efficacy, however mPEG can induce anti-PEG antibodies that negatively impact their therapeutic effects. Here, the authors determine the co-crystal structure of the humanized 15-2b anti-mPEG antibody with mPEG, providing insights into understanding mPEG-binding specificity and antigenicity of anti-mPEG antibodies.

The RquA protein is required for rhodoquinone biosynthesis; however, its exact function is not yet known. Here, the authors demonstrate that RquA is homologous to SAM-dependent methyltransferases but functions as an aminotransferase using Mn²⁺ as cofactor to convert ubiquinone to rhodoquinone.

Caprazamycin is a nucleoside antibiotic that can interrupt bacterial peptidoglycan biosynthesis, but the biosynthesis of caprazamycin is not fully understood yet. Here, the authors characterize five key enzymes from caprazamycin/muraymycin gene cluster, particularly nonheme αKG-dependent enzyme Cpz10 as a β-hydroxylase that recruits two iron atoms and leads to caprazamycin formation.

Current crystal structure prediction methods for anticipating polymorphism are lacking in their ability to provide information on the depth of each energy minimum and the possible transition paths and energy barriers between polymorph structures. Here, a Monte Carlo threshold algorithm is applied to four polymorphic organic systems to estimate the energy barriers that separate the different polymorph structures and characterise the global structure of the energy landscapes of their molecular crystal structures.

Adiabatic state preparation (ASP) can generate correlated wave functions for quantum chemical calculations, but is inherently unsuitable for studying strongly correlated systems. Here, the authors perform numerical simulations of ASP for the ground state wave functions of molecules with strongly correlated electrons and propose practical conditions for preparation of close-to-exact correlated wave functions.

Understanding the mechanisms of virus-induced cell modifications is critical for the development of diagnostics and antiviral treatments. Here, confocal Raman microspectroscopy is demonstrated to be a useful tool to study biochemical modifications in cells caused by SARS-CoV-2 infection.