Two-dimensional hexagonal materials such as transition metal dichalcogenides exhibit valley degrees of freedom, offering fascinating potential for valley-based quantum computing and optoelectronics. In nonlinear optics, the K and K' valleys provide excitation resonances that can be used for ultrafast control of excitons, Bloch oscillations, and Floquet physics. Under intense laser fields, however, the role of coherent carrier dynamics away from the K/K' valleys is largely unexplored. In this study, we observe quantum interferences in high harmonic generation from monolayer $WS_2$ as laser fields drive electrons from the valleys across the full Brillouin zone. In the perturbative regime, interband resonances at the valleys enhance high harmonic generation through multi-photon excitations. In the strong-field regime, the high harmonic spectrum is sensitively controlled by light-driven quantum interferences between the interband valley resonances and intraband currents originating from electrons occupying various points in the Brillouin zone, also away from K/K' valleys such as $\Gamma$ and M. Our experimental observations are in strong agreement with quantum simulations, validating their interpretation. This work proposes new routes for harnessing laser-driven quantum interference in two-dimensional hexagonal systems and all-optical techniques to occupy and read-out electronic structures in the full Brillouin zone via strong-field nonlinear optics, advancing quantum technologies.

A library of eight new fluoroquinolone-nuclease conjugates containing a guanidinoethyl or aminoethyl auxiliary pendant on the 1,4,7-triazacyclononane (TACN) moiety was designed and synthesized to investigate their potential as catalytic antibiotics. The Cu(II) complexes of the designer structures showed significant in vitro hydrolytic and oxidative DNA cleaving activity and good antibacterial activity against both Gram-negative and Gram-positive bacteria. The observed activity of all the Cu(II)-TACN-ciprofloxacin complexes was strongly inhibited in the presence of Cu(II)-chelating agents, thereby demonstrating the “vulnerability” under physiological conditions. However, selected TACN-ciprofloxacin conjugates in their metal-free form efficiently cleaved plasmid DNA under physiological conditions. The lead compound 1 showed good DNase activity which was retained in the presence of strong metal chelators and exhibited excellent antibacterial activity against both Gram-negative and Gram-positive bacteria. Density functional theory calculations combined with quantum mechanics/molecular mechanics simulations suggest a general base-general acid mechanism for the hydrolytic DNA cleavage mechanism by compound 1.

Proton transfer (PT) is at the heart of fundamental natural biochemical reactions, e.g. in bioenergetics, where proteins are the main proton mediators. PT between two specific points requires a change in the proton motive force via alteration of acid-base properties. Nature solved this problem primarily by modulating the protein structure during the PT process. Here, we introduce a light-triggered proton donor-bridge-acceptor approach for inducing and visualizing directional PT in biosystems, specifically peptides. To do so, we synthesize unnatural amino acids containing a light-triggered proton donor and acceptor and place them at the ends of peptide bridges that differ in their amino acid composition while creating a giant ΔpKa* gradient between them upon photoexcitation. Ultrafast optical spectroscopies allow for visualization of the PT process across the donor-bridge-acceptor system and extraction of the PT kinetics. Our results reveal the importance of side chains, peptide structure, and environment in promoting PT. We show that helical structures can promote PT even with hydrophobic side chains, whereas titratable oxo-amino-acids can promote PT via their side chains even in an aprotic environment. Our strategy for inducing and visualizing the PT process across any desired pathway can be extended to various peptide systems and into proteins, thus opening a new field of research.

Gathering information about a system enables greater control over it. This principle lies at the core of information engines, which use measurement-based feedback to rectify thermal noise and convert information into work. Originating from Maxwell's and Szilárd's thought experiments, the thermodynamics of information engines has steadily advanced, with recent experimental realizations pushing the field forward. Coupled with technological advances and developments in nonequilibrium thermodynamics, novel implementations of information engines continue to challenge theoretical understanding. In this perspective, we discuss recent progress and highlight new opportunities, such as applying information engines to active, many-body, and inertial systems and leveraging tools like optimal control to design their driving protocols.

We report a fully stereocontrolled synthesis of previously unknown unsaturated polyacetals through an iteration of two steps: (1) Pd-catalyzed hydroalkoxylation of alkoxyallenes; and (2) base-mediated isomerization of propargyl ethers into alkoxyallenes. Site- and stereoselective alkene isomerization of the capping allyl group initiates a domino-Coates–Claisen rearrangement, which completely rearranges the iteratively assembled backbone with the stereochemistry of the newly formed stereocentres controlled by the configuration of the acetal centres in the starting materials. The resulting products feature multiple stereocentres in a 1,3-relationship, which map onto a broad range of bioactive natural products, including deoxypropionates.

Exceptional points are remarkable features of open quantum systems, such as photo-ionizing or photo-dissociating molecules, amplified or dissipated light states in photonic structures, and many others. These points mark spectral degeneracies in a system's parameter space where the eigenstates become non-orthogonal, enabling precise control over decay rates, topological transitions in parity-time (PT)-symmetric systems, or boosting the system's sensitivity to external stimuli. Here we show that exceptional points can be enantiosenstive, enabling a new type of control over topological and chiral properties of non-Hermitian open chiral systems. We apply the concept of enantio-sensitive exceptional points to demonstrate a broad range of phenomena, from enantiosensitive topological population transfer, to lifetime branching in resonant photo-decay of chiral molecules, to enhanced chiral sensing in optical fibers. Our results combine high enantiosensitivity with topological robustness in chiral discrimination and separation, paving the way for new approaches in the control of non-Hermitian and chiral phenomena.

The synthesis of the first isolable geminal 1,1-dilithiostannane is reported. In the solid state, the novel 1,1- dilithiostannane has three different structural motifs, depending on the reaction conditions used for its synthesis: (1) an unsolvated co-aggregate consisting of two 1,1-dilithiostannane molecules and two silyllithium molecules, {[(tBu2MeSi)2SnLi2]2∙[tBu2MeSiLi]2}; (2) a solvated trimeric stannyllithium dianion {[(tBu2MeSi)2Sn]3Li4}2- associated with two fully dissociated THF-solvated Li+ cations; (3) a THF-solvated contact-ion pair dimer of 1,1-dilithiostannane, [(tBu2MeSi)2SnLi2]2∙(THF)4.

A dinuclear Cu-peptoid, Cu₂(BDiE)₂, having a diol side chain was developed as a homogeneous electrocatalyst for oxygen evolution reaction (OER) at neutral pH. The molecular structure of Cu₂(BDiE)₂ was characterized and concluded by ESI-MS, UV–vis, and single-crystal X-ray diffraction. Electrochemical, spectroscopic, and mechanistic studies revealed that borate buffer (the solution medium) has a minor effect during electrocatalysis; however, the diol side chain promotes a second coordination sphere effect via multiple hydrogen bonds which highly stabilize the complex, leading to an OER. Based on these observations and the collected data, we also suggest two different and unique mechanism pathways: a major one, which involves interactions of radical intermediates, which is buffer independent, and a minor one that resembles water nucleophilic attack (WNA) and is assisted by the borate buffer.

Crossing the blood–brain barrier (BBB) and reaching intracranial tumours is a clinical challenge for current targeted interventions including antibody-based therapies, contributing to poor patient outcomes. Increased cell surface density of human epidermal growth factor receptor 3 (HER3) is associated with a growing number of metastatic tumour types and is observed on tumour cells that acquire resistance to a growing number of clinical targeted therapies. Here we describe the evaluation of HER3-homing nanobiological particles (nanobioparticles (NBPs)) on such tumours in preclinical models and our discovery that systemic NBPs could be found in the brain even in the absence of such tumours. Our subsequent studies described here show that HER3 is prominently associated with both mouse and human brain endothelium and with extravasation of systemic NBPs in mice and in human-derived BBB chips in contrast to non-targeted agents. In mice, systemically delivered NBPs carrying tumoricidal agents reduced the growth of intracranial triple-negative breast cancer cells, which also express HER3, with improved therapeutic profile compared to current therapies and compared to agents using traditional BBB transport routes. As HER3 associates with a growing number of metastatic tumours, the NBPs described here may offer targeted efficacy especially when such tumours localize to the brain.

The Michael addition of unactivated nitriles to α,β-unsaturated ketones is a challenging yet desirable strategy for installing alkyl cyano-groups (R-CN) in organic molecules. However, despite formidable efforts, using acetonitrile as a Michael donor in these reactions has remained a significant challenge. Herein, we report a highly active manganese(I) complex [(PCNHCP)Mn(CO)2H] (1), which chemoselectively catalyzes the 1,4-addition of unactivated nitriles (incl. acetonitrile) to α,β-unsaturated ketones. The developed methodology operates under mild conditions, does not require any additives or bases, features low catalyst loadings (1 mol %), fast reaction times (2-8 hours), and is compatible with a wide variety of functional groups, including halides, trifluoromethyl, alkenyl, alkynyl, and (hetero)aryl groups. Extensive mechanistic studies revealed that after base-free activation of the nitrile, either the N-bound manganese-ketenimine (propionitrile or benzyl cyanide) or the C-bound manganese-cyanoalkyl (acetonitrile) complex is formed. The difference in stability of these two species explains why more sterically hindered and presumably less activated nitriles (i.e., propionitrile, and butyronitrile) show higher reactivity than their corresponding more activated congeners (i.e., acetonitrile). Finally, the practicality of our approach was demonstrated through a gram-scale reaction and subsequent derivatizations of the obtained product into important organic motifs such as ene-lactams and tetrahydropyridines