Enantiomer-dependent immunological response to chiral nanoparticles.

Chirality is a unifying structural metric of biological and abiological forms of matter. Over the past decade, considerable clarity has been achieved in understanding the chemistry and physics of chiral inorganic nanoparticles1-4; however, little is known about their effects on complex biochemical networks5,6. Intermolecular interactions of biological molecules and inorganic nanoparticles show some commonalities7-9, but these structures differ in scale, in geometry and in the dynamics of chiral shapes, which can both impede and strengthen their mirror-asymmetric complexes. Here we show that achiral and left- and right-handed gold biomimetic nanoparticles show different in vitro and in vivo immune responses. We use irradiation with circularly polarized light (CPL) to synthesize nanoparticles with controllable nanometre-scale chirality and optical anisotropy factors (g-factors) of up to 0.4. We find that binding of nanoparticles to two proteins from the family of adhesion G-protein-coupled receptors (AGPCRs)-namely cluster-of-differentiation 97 (CD97) and epidermal-growth-factor-like-module receptor 1 (EMR1)-results in the opening of mechanosensitive potassium-efflux channels, the production of immune signalling complexes known as inflammasomes, and the maturation of mouse bone-marrow-derived dendritic cells. Both in vivo and in vitro immune responses depend monotonically on the g-factors of the nanoparticles, indicating that nanoscale chirality can be used to regulate the maturation of immune cells. Finally, left-handed nanoparticles show substantially higher (1,258-fold) efficiency compared with their right-handed counterparts as adjuvants for vaccination against the H9N2 influenza virus, opening a path to the use of nanoscale chirality in immunology.

Mechanism of high-mannose N-glycan breakdown and metabolism by Bifidobacterium longum.

Bifidobacteria are early colonizers of the human gut and play central roles in human health and metabolism. To thrive in this competitive niche, these bacteria evolved the capacity to use complex carbohydrates, including mammalian N-glycans. Herein, we elucidated pivotal biochemical steps involved in high-mannose N-glycan utilization by Bifidobacterium longum. After N-glycan release by an endo-ß-N-acetylglucosaminidase, the mannosyl arms are trimmed by the cooperative action of three functionally distinct glycoside hydrolase 38 (GH38) α-mannosidases and a specific GH125 α-1,6-mannosidase. High-resolution cryo-electron microscopy structures revealed that bifidobacterial GH38 α-mannosidases form homotetramers, with the N-terminal jelly roll domain contributing to substrate selectivity. Additionally, an α-glucosidase enables the processing of monoglucosylated N-glycans. Notably, the main degradation product, mannose, is isomerized into fructose before phosphorylation, an unconventional metabolic route connecting it to the bifid shunt pathway. These findings shed light on key molecular mechanisms used by bifidobacteria to use high-mannose N-glycans, a perennial carbon and energy source in the intestinal lumen.

Experimental and Theoretical DFT Study of Cu(I)/N,N-Disubstituted-N'-acylthioureato Anticancer Complexes: Actin Cytoskeleton and Induction of Death by Apoptosis in Triple-Negative Breast Tumor Cells.

Six complexes with the general formula [Cu(acylthioureato)(PPh3)2] were synthesized and characterized using spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), mass spectrometry, elemental analysis, and X-ray diffraction. Interpretation of the in vitro cytotoxicity data of Cu(I) complexes took into account their stability in cell culture medium. DFT calculations showed that NMR properties, such as the shielding of carbon atoms, are affected by relativistic effects, supported by the ZORA Hamiltonian in the theoretical calculations. Additionally, the calculation of the energies of the frontier molecular orbitals predicted that the structural changes of the acylthiourea ligands did not cause marked changes in the reactivity descriptors. All complexes were cytotoxic to the evaluated tumor cell lines [MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast cancer), and A549 (lung cancer)]. In the MDA-MB-231 cell line, complex 1 significantly altered the cytoskeleton of the cells, reducing the density and promoting the condensation of F-actin filaments. In addition, the compound caused an increase in the percentage of cells in the fragmented DNA region (sub-G0) and induced cell death via the apoptotic pathway starting at the IC50 concentration. Taken together, the results show that complex 1 has cytotoxic and apoptotic effects on TNBC cells, which is a cell line originating from an aggressive, difficult-to-treat breast cancer.

Graphitic carbon nitrides as platforms for single-atom photocatalysis.

Herein we demonstrate that adding single atoms of selected transition metals to graphitic carbon nitrides allows the tailoring of the electronic and chemical properties of these 2D nanomaterials, directly impacting their usage in photocatalysis. These single-atom photocatalysts were successfully prepared with Ni2+, Pt2+ or Ru3+ by cation exchange, using poly(heptazine imides) (PHI) as the 2D layered platform. Differences in photocatalytic performance for these metals were assessed using rhodamine-B (RhB) and methyl orange (MO) as model compounds for degradation. We have demonstrated that single atoms may either improve or impair the degradation of RhB and MO, depending on the proper matching of the net charge of these molecules and the surface potential of the catalyst, which in turn is responsive to the metal incorporated into the PHI nanostructures. Computer simulations demonstrated that even one transition metal cation caused dramatic changes in the electronic structure of PHI, especially regarding light absorption, which was extended all along the visible up to the near IR region. Besides introducing new quantum states, the metal atoms strongly polarized the molecular orbitals across the PHI and electrostatic fields arising from the electronic transitions became at least tenfold stronger. This simple proof of concept demonstrates that these new materials hold promise as tools for many important photocatalytic reactions that are strongly dependent on our ability to control surface charge and its polarization under illumination, such as H2 evolution, CO2 reduction and photooxidation in general.

How lignin sticks to cellulose-insights from atomic force microscopy enhanced by machine-learning analysis and molecular dynamics simulations.

Elucidating cellulose-lignin interactions at the molecular and nanometric scales is an important research topic with impacts on several pathways of biomass valorization. Here, the interaction forces between a cellulosic substrate and lignin are investigated. Atomic force microscopy with lignin-coated tips is employed to probe the site-specific adhesion to a cellulose film in liquid water. Over seven thousand force-curves are analyzed by a machine-learning approach to cluster the experimental data into types of cellulose-tip interactions. The molecular mechanisms for distinct types of cellulose-lignin interactions are revealed by molecular dynamics simulations of lignin globules interacting with different cellulose Iß crystal facets. This unique combination of experimental force-curves, data-driven analysis, and molecular simulations opens a new approach of investigation and updates the understanding of cellulose-lignin interactions at the nanoscale.

Emergence of complexity in hierarchically organized chiral particles.

The structural complexity of composite biomaterials and biomineralized particles arises from the hierarchical ordering of inorganic building blocks over multiple scales. Although empirical observations of complex nanoassemblies are abundant, the physicochemical mechanisms leading to their geometrical complexity are still puzzling, especially for nonuniformly sized components. We report the self-assembly of hierarchically organized particles (HOPs) from polydisperse gold thiolate nanoplatelets with cysteine surface ligands. Graph theory methods indicate that these HOPs, which feature twisted spikes and other morphologies, display higher complexity than their biological counterparts. Their intricate organization emerges from competing chirality-dependent assembly restrictions that render assembly pathways primarily dependent on nanoparticle symmetry rather than size. These findings and HOP phase diagrams open a pathway to a large family of colloids with complex architectures and unusual chiroptical and chemical properties.

Chiral recognition of liquid phase dimers from gamma-valerolactone racemic mixture.

Gamma-valerolactone (GVL) is a cyclic ester that can be considered a green alternative in chemical processes due to its environmentally friendly physical and chemical properties and low production cost from biomass. Although GVL is a chiral solvent, it is usually used as a racemic mixture, instead of its homochiral forms, which might improve its performance in enantioselective synthesis and chiral separation chromatographic techniques. This report presents the development and validation of an atomistic force field optimized to reproduce GVL liquid-phase properties via Monte Carlo (MC) and molecular dynamics (MD) simulation methods. The optimized force field improved the description of the interactions between pairs of molecules, which is a key aspect for a proper assessment of subtle interactions between the enantiomeric forms of GVL. Inspection of radial distribution functions (RDF) for correlations between RR, SS, and RS interactions found within GVL racemic mixture shows very subtle differences at the first solvation shell. Average interaction energies [Formula: see text], [Formula: see text] and [Formula: see text] for RR, SS, and RS dimer ensembles, respectively, were calculated with force field and also HF-3c and PBEh-3c quantum chemistry methods. For each methodology, resulting values obtained for [Formula: see text] and [Formula: see text] were almost the same and more negative than [Formula: see text]. Also, the average energy fluctuation obtained for RR and SS dimers were higher than the one obtained for RS.

Site-selective photoinduced cleavage and profiling of DNA by chiral semiconductor nanoparticles.

Gene editing is an important genetic engineering technique that enables gene manipulation at the molecular level. It mainly relies on engineered nucleases of biological origin, whose precise functions cannot be replicated in any currently known abiotic artificial material. Here, we show that chiral cysteine-modified CdTe nanoparticles can specifically recognize and, following photonic excitation, cut at the restriction site GAT'ATC (' indicates the cut site) in double-stranded DNA exceeding 90 base pairs, mimicking a restriction endonuclease. Although photoinduced reactive oxygen species are found to be responsible for the cleavage activity, the sequence selectivity arises from the affinity between cysteine and the conformation of the specific DNA sequence, as confirmed by quantum-chemical calculations. In addition, we demonstrate non-enzymatic sequence-specific DNA incision in living cells and in vivo using these CdTe nanoparticles, which may help in the design of abiotic materials for gene editing and other biological applications.