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Organic thermoelectric materials are promising for wearable heating and cooling devices, as well as near-room-temperature energy generation, due to their nontoxicity, abundance, low cost, and flexibility. However, their primary challenge preventing widespread use is their reduced figure of merit (zT) caused by low electrical conductivity. This study presents a method to enhance the thermoelectric performance of solution-processable organic materials through confined crystallization using the lithographically controlled wetting (LCW) technique. Using PEDOT as a benchmark, we demonstrate that controlled crystallization at the nanoscale improves electrical conductivity by optimizing chain packing and grain morphology. Structural characterizations reveal the formation of a highly compact PEDOT arrangement, achieved through a combination of confined crystallization and DMSO post-treatment, leading to a 4-fold increase in the power factor compared to spin-coated films. This approach also reduces the thermal conductivity dependence on electrical conductivity, improving the zT by up to 260%. The LCW technique, compatible with large-area and flexible substrates, offers a simple, green, and low-cost method to boost the performance of organic thermoelectrics, advancing the potential for sustainable energy solutions and advanced organic electronic devices.

Improving the use of platinum in propane dehydrogenation catalysts is a crucial aspect to increasing the efficiency and sustainability of propylene production. A known and practiced strategy involves incorporating more abundant metals in supported platinum catalysts, increasing its activity and stability while decreasing the overall loading. Here, using colloidal techniques to control the size and composition of the active phase, we show that Pt/Cu alloy nanoparticles supported on alumina (Pt/Cu/Al 2 O 3 ) displayed elevated rates for propane dehydrogenation at low temperature compared to a monometallic Pt/Al 2 O 3 catalyst. We demonstrate that the enhanced catalytic activity is correlated with a higher surface Cu content and formation of a Pt-rich core and Cu-rich shell that isolates Pt sites and increases their intrinsic activity. However, rates declined on stream because of dynamic metal diffusion processes that led to a more uniform alloy structure. This transformation was only partially inhibited by adding excess hydrogen to the feed stream. Instead, cobalt was introduced to provide trimetallic Pt/Cu/Co catalysts with stabilized surface structure and stable activity and higher rates than the original Pt/Cu system. The structure-activity relationship insights in this work offer improved knowledge of propane dehydrogenation catalyst development featuring reduced Pt loadings and notable thermal stability for propylene production.

A multiscale model based on the coupling of the multiconfigurational self-consistent field (MCSCF) method and the classical atomistic polarizable fluctuating charges (FQ) force field is presented. The resulting MCSCF/FQ approach is validated by exploiting the CASSCF scheme through application to compute vertical excitation energies of formaldehyde and para -nitroaniline in aqueous solution. The procedure is integrated with molecular dynamics simulations to capture the solute's conformational changes and the dynamic aspects of solvation. Comparative analysis with alternative solvent models, gas-phase calculations, and experimental data provides insights into the model's accuracy in reproducing solute-solvent molecular interactions and spectral signals.

Multicellular cable bacteria display an exceptional form of biological conduction, channeling electric currents across centimeter distances through a regular network of protein fibers embedded in the cell envelope. The fiber conductivity is among the highest recorded for biomaterials, but the underlying mechanism of electron transport remains elusive. Here, we performed detailed characterization of the conductance from room temperature down to liquid helium temperature to attain insight into the mechanism of long-range conduction. A consistent behavior is seen within and across individual filaments. The conductance near room temperature reveals thermally activated behavior, yet with a low activation energy. At cryogenic temperatures, the conductance at moderate electric fields becomes virtually independent of temperature, suggesting that quantum vibrations couple to the charge transport through nuclear tunneling. Our data support an incoherent multistep hopping model within parallel conduction channels with a low activation energy and high transfer efficiency between hopping sites. This model explains the capacity of cable bacteria to transport electrons across centimeter-scale distances, thus illustrating how electric currents can be guided through extremely long supramolecular protein structures.

Composite biomaterials with excellent biocompatibility and biodegradability are crucial in tissue engineering. In this work, a composite protein and polysaccharide photo-cross-linkable hydrogel was prepared using silk fibroin methacrylate (SFMA) and hyaluronic acid methacrylate (HAMA). SFMA was obtained by the methacrylation of degummed SF with glycidyl methacrylate (GMA), while HA was methacrylated by 2-aminoethyl methacrylate hydrochloride (AEMA). We investigated the effect of the addition of 1 wt % HAMA to 5, 10, and 20 wt % SFMA, which resulted in an increase in both static and cycling mechanical strengths. All composite hydrogels gelled under UV light in <30 s, allowing for rapid stabilization and stiffness increases. The biocompatibility of the hydrogels was confirmed by direct and indirect contact methods and by evaluation against the NIH3T3 and MC3T3 cell lines with a live-dead assay by confocal imaging. The range of obtained mechanical properties from developed composite and UV-cross-linkable hydrogels sets the basis as possible future biomaterials for various biomedical applications.

Aerolysin is a bacterial toxin that forms transmembrane pores at the host plasma membrane and has a narrow internal diameter and great stability. These assets make it a highly promising nanopore for detecting biopolymers such as nucleic acids and peptides. Although much is known about aerolysin from a microbiological and structural perspective, its membrane association and pore-formation mechanism are not yet fully understood. Here, we used angle-resolved second harmonic scattering (AR-SHS) and single-channel current measurements to investigate how wild-type (wt) aerolysin and its mutants interact with liposomes in aqueous solutions at femtomolar concentrations. Our AR-SHS experiments were sensitive enough to detect changes in the electrostatic properties of membrane-bound aerolysin, which were induced by variations in pH levels. We reported for the first time the membrane binding affinity of aerolysin at different stages of the pore formation mechanism: while wt aerolysin has a binding affinity as high as 20 fM, the quasi-pore and the prepore states show gradually decreasing membrane affinities, incomplete insertion, and a pore opening signature. Moreover, we quantitatively characterized the membrane affinity of mutants relevant for applications to nanopore sensing. Our study provides a label-free method for efficiently screening biological pores suitable for conducting molecular sensing and sequencing measurements as well as for probing pore-forming processes.

Next-generation data networks need to support Tb/s rates. In-phase and quadrature (IQ) modulation combine phase and intensity information to increase the density of encoded data, reduce overall power consumption by minimizing the number of channels, and increase noise tolerance. To reduce errors when decoding the received signal, intersymbol interference must be minimized. This is achieved with pure phase modulation, where the phase of the optical signal is controlled without changing its intensity. Phase modulators are characterized by the voltage required to achieve a π phase shift, V π , the device length, L , and their product, V π L . To reduce power consumption, IQ modulators are needed with <1 V drive voltages and compact (sub-cm) dimensions, which translate in V π L < 1Vcm. Si and LiNbO 3 (LN) IQ modulators do not currently meet these requirements because V π L > 1Vcm. Here, we report a double single-layer graphene (SLG) Mach-Zehnder modulator (MZM) with pure phase modulation in the transparency regime, where optical losses are minimized and remain constant with increasing voltage. Our device has V π L ∼ 0.3Vcm, matching state-of-the-art SLG-based MZMs and plasmonic LN MZMs, but with pure phase modulation and low insertion loss (∼5 dB), essential for IQ modulation. Our V π L is ∼5 times lower than the lowest thin-film LN MZMs and ∼3 times lower than the lowest Si MZMs. This enables devices with complementary metal-oxide semiconductor compatible V π L (<1Vcm) and smaller footprint than LN or Si MZMs, improving circuit density and reducing power consumption by 1 order of magnitude.

Bacteria are a treasure trove of metabolic reactions, but most industrial biotechnology applications rely on a limited set of established host organisms. In contrast, adopting nonmodel bacteria for the production of various chemicals of interest is often hampered by their limited genetic amenability coupled with their low transformation efficiency. In this study, we propose a series of steps that can be taken to increase electroporation efficiency in nonmodel bacteria. As a test strain, we use Cupriavidus necator H16, a lithoautotrophic bacterium that has been engineered to produce a wide range of products from CO 2 and hydrogen. However, its low electroporation efficiency hampers the high-throughput genetic engineering required to develop C. necator into an industrially relevant host organism. Thus, conjugation has often been the method of choice for introducing exogenous DNA, especially when introducing large plasmids or suicide plasmids. We first propose a species-independent technique based on natively methylated DNA and Golden Gate assembly to increase one-pot cloning and electroporation efficiency by 70-fold. Second, bioinformatic tools were used to predict defense systems and develop a restriction avoidance strategy that was used to introduce suicide plasmids by electroporation to obtain a domesticated strain. The results are discussed in the context of metabolic engineering of nonmodel bacteria.

Studying ionic liquids (ILs) through computational methods is one of the ways to accelerate progress in the design of novel and potentially green materials optimized for task-specific applications. Therefore, it is essential to develop simple and cost-effective computational procedures that are able to replicate and predict experimental data. Among these, spectroscopic measurements are of particular relevance since they are often implicated in structure-property relationships, especially in the infrared spectral region, where characteristic absorption and scattering processes due to molecular vibrations are ultimately influenced by the surrounding environment in the condensed phase. In this frame, we validate, vis-à-vis experimental data, an efficient theoretical method to compute the Raman spectra in the liquid phase of four especially synthesized dicationic ionic liquids and to assess the conformational cation/anion contributions to the experimental bands. The computational procedure is based on the assessment of the most probable conformations as evaluated by a computational protocol involving both molecular dynamics and ab initio methods.

Shedding light on the interaction between inorganic nanoparticles (NPs) and living microorganisms is at the basis of the development of biohybrid technologies with improved performance. Au NPs have been shown to be able to improve the extracellular electron transfer (EET) in intact bacterial cells interfaced with an electrode; however, detailed information on the role of NP-surface properties in their interaction with bacterial membranes is still lacking. Herein, we unveil how the surface functionalization of Au NPs influences their interaction with photosynthetic bacteria, focusing on cell morphology, growth kinetics, NPs localization, and electrocatalytic performance. We show that functionalization of Au NPs with cysteine in the zwitterionic form results in a uniform NPs distribution in purple bacteria, specifically locating the NPs within the outer-membrane/periplasmic space of bacterial cells. These biohybrid cells, when coupled with an electrode, exhibit enhanced EET and increased (photo)current generation, paving the way for the future development of rationally designed biohybrid electrochemical systems.

A novel oxygen evolution reaction (OER) electrocatalyst was prepared by a synthesis strategy consisting of the solvothermal growth of Ni 3 S 2 nanostructures on Ni foam, followed by hydrothermal incorporation of Fe species (Fe-Ni 3 S 2 /Ni foam). This electrocatalyst displayed a low OER overpotential of 230 mV at 100 mA·cm -2 , a low Tafel slope of 43 mV·dec -1 , and constant performance at an industrially relevant current density (500 mA·cm -2 ) over 100 h in a 1.0 M KOH electrolyte, despite a minor loss of Fe in the process. Based on a detailed characterization by (in situ) Raman spectroscopy, (quasi-in situ) XPS, SEM, TEM, XRD, ICP-AES, EIS, and C dl analysis, the high OER activity and stability of Fe-Ni 3 S 2 /Ni foam were attributed to the nanostructuring of the surface in the form of stable nanosheets and to the combination of Ni 3 S 2 granting suitable electrical conductivity with newly formed NiFe-based (oxy)hydroxides at the surface of the material providing the active sites for OER.

Biofilm formation in common public places and hospitals is of great concern. Active antimicrobial coatings can prevent the formation of bacterial biofilms and the spreading of primary and secondary infections caused by contagious bacteria and viruses. In the present work, we report a simple spray coating process using copper oxide (CuO) nanoparticles (NPs) dispersed in a titanium dioxide (TiO 2 ) sol, where CuONPs act as the active antimicrobial agent and TiO 2 as the inorganic binder. Homogeneous CuONPs/TiO 2 coating was obtained on polypropylene substrates by spraying the CuO/TiO 2 sol using a commercial air gun, followed by drying at 80 °C. The amount of CuONPs loading in the coating was adjusted by controlling the number of coated layers. CuONPs and CuONPs/TiO 2 coatings were characterized by XRD, BET, X-ray fluorescence spectroscopy, AFM, and field emission scanning electron microscopy techniques. All of the coated films showed dual activity, i.e., antimicrobial and superhydrophobicity. A high bactericidal effect against both Escherichia coli and Staphylococcus aureus was observed for the coated substrates. Coatings with higher CuONPs showed greater antibacterial activity, reaching R value >6, and no bacterial colonies were detected after 24 h of incubation. An increasing trend of water contact angle was observed with the increasing amount of CuONP loading., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

With nearly 700 structures solved and a growing number of customized structure prediction algorithms being developed at a fast pace, G protein-coupled receptors (GPCRs) are an optimal test case for validating new approaches for the prediction of receptor active state and ligand bioactive conformation complexes. In this study, we leveraged the availability of hundreds of peptide GPCRs in the active state and both classical homology and artificial intelligence (AI) based protein modeling combined with docking and AI-based peptide structure prediction approaches to predict the nociceptin/orphanin FQ-NOP receptor active state complex (N/OFQ-NOPa). The In Silico generated hypotheses were validated via the design, synthesis, and pharmacological characterization of novel linear N/OFQ(1-13)-NH 2 analogues, leading to the discovery of a novel antagonist ( 3B ; p K B = 6.63) bearing a single ring-constrained residue in place of the Gly 2 -Gly 3 motif of the N/OFQ message sequence (FGGF). While the experimental validation was ongoing, the availability of the Cryo-EM structure of the predicted complex enabled us to unambiguously validate the generated hypotheses. To the best of our knowledge, this is the first example of a peptide-GPCR complex predicted with atomistic accuracy (full complex Cα RMSD < 1.0 Å) and of the N/OFQ message moiety being successfully modified with a rigid scaffold.

The reductive catalytic fractionation (RCF) of second generation lignocellulosic biomass is an elegant one-pot process to obtain a highly delignified cellulose pulp, sugar-derived polyols, and depolymerized and stabilized lignin oils. However, the need of noble metal catalysts to prompt the reactions may impact the economic sustainability of the overall "lignin-first" biorefinery if the catalyst recovery and recyclability are not guaranteed. Herein, the use of a novel catalyst based on supported ruthenium over maghemite for the RCF of poplar sawdust is reported for the first time. This material allows us to obtain a pure cellulose pulp with a quantitative magnetic recovery efficiency after the first cycle. The obtained lignin oil is composed by a 12% yield in phenolic monomers (i.e., benzyl alcohol, 4- n -propylguaiacol, and 4- n -propylsyringol), together with dimers and trimers as confirmed by GPC analyses. The catalytic material was found to be stable and recyclable for three reaction cycles with only minor loss of RCF efficiency. On the other hand, the straightforward, lab-scale, magnetic recovery procedure needs to be further improved in the future to ensure quantitative recovery of the catalyst also after several RCF cycles., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

ALK5 inhibitors represent an attractive therapeutic approach for the treatment of a variety of pathologies, including cancer and fibrosis. Herein, we report the design and in vitro characterization of a novel series of ALK5 modulators featuring a 4,6-disubstituted pyridazine core. A knowledge-based scaffold-hopping exploration was initially conducted on a restricted set of heteroaromatic cores using available ligand- and structure-based information. The most potent structurally novel hit compound 2A was subsequently subjected to a preliminary optimization for the inhaled delivery, applying physicochemical criteria aimed at minimizing systemic exposure to limit the risk of adverse side effects. The resulting inhibitors showed a marked boost in potency against ALK5 and in vitro ADME properties, potentially favoring lung retention. The optimized hits 20 and 23 might thus be considered promising starting points for the development of novel inhaled ALK5 inhibitors., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Light-induced ordered states can emerge in materials after irradiation with ultrafast laser pulses. However, their prediction is challenging because the inverted band occupation confounds our chemical intuition. Hence, we use a recently developed constrained density functional perturbation theory approach to systematically screen single-layer transition metal dichalcogenides (TMDs) for light-induced ordered states. We demonstrate that all examined single-layer TMDs reveal similar light-induced charge orderings. The corresponding reconstructions are periodic arrangements of polarons (polaronic crystals), characterized by triangular metal clusters and having no equivalent at equilibrium conditions. The polarons are accompanied by localized midgap states in the electronic band structure, detectable by experimental methods. We assess the selenides as the most promising candidates for potential photoexcitation experiments because they transition at low critical fluences, have low transition barriers, and maintain an open band gap under photoexcitation. Our work paves the way for innovative material design approaches targeting light-induced phases.

Gamma aminobutyric acid type A receptors (GABA A Rs) play a key role in the mammalian central nervous system (CNS) as drivers of neuroinhibitory circuits, which are commonly targeted for therapeutic purposes with potentiator drugs. However, due to their widespread expression and strong inhibitory action, systemic pharmaceutical potentiation of GABA A Rs inevitably causes adverse effects regardless of the drug selectivity. Therefore, therapeutic guidelines must often limit or exclude clinically available GABA A R potentiators, despite their high efficacy, good biodistribution, and favorable molecular properties. One solution to this problem is to use drugs with light-dependent activity (photopharmacology) in combination with on-demand, localized illumination. However, a suitable light-activated potentiator of GABA A Rs has been elusive so far for use in wildtype mammals. We have met this need by developing azocarnil, a diffusible GABAergic agonist-potentiator based on the anxiolytic drug abecarnil that is inactive in the dark and activated by visible violet light. Azocarnil can be rapidly deactivated with green light and by thermal relaxation in the dark. We demonstrate that it selectively inhibits neuronal currents in hippocampal neurons in vitro and in the dorsal horns of the spinal cord of mice, decreasing the mechanical sensitivity as a function of illumination without displaying systemic adverse effects. Azocarnil expands the in vivo photopharmacological toolkit with a novel chemical scaffold and achieves a milestone toward future phototherapeutic applications to safely treat muscle spasms, pain, anxiety, sleep disorders, and epilepsy.

A comprehensive understanding of electron-photon correlation is essential for describing the reshaping of molecular orbitals in quantum electrodynamics (QED) environments. The strong coupling QED Hartree-Fock (SC-QED-HF) theory tackles these aspects by providing consistent molecular orbitals in the strong coupling regime. The previous implementation, however, has significant convergence issues that limit the applicability. In this work, we introduce two second-order algorithms that significantly reduce the computational requirements, thereby enhancing the modeling of large molecular systems in QED environments. Furthermore, the implementation will enable the development of correlated methods based on a reliable molecular orbital framework as well as multi-level methodologies able to model the inclusion of solvent effects in this kind of complex systems.

Metalloporphyrins based on open-shell transition metals, such as Ni(II), exhibit typically fast excited-state relaxation. In this work, we shed light into the nonradiative relaxation mechanism in a nanographene-Ni(II) porphyrin conjugate. Variable temperature transient absorption and global fit analysis are combined to produce a picture of the relaxation pathways. At room temperature, photoexcitation of the lowest π-π* transition is followed by vibrational cooling in 1.6 ps, setting a short 20 ps temporal window wherein a small fraction of relaxed singlets radiatively decay to the ground state before intersystem crossing proceeds. Following intersystem crossing, triplets relax rapidly to the ground state (S 0 ) in a few tens of picoseconds. By performing measurements at low temperature, we provide evidence for a competition between two terminal relaxation pathways from the lowest (metal-centered) triplet to the ground state: a slow ground state relaxation process proceeding in time scales beyond 1.6 ns and a faster pathway dictated by a sloped conical intersection, which is thermally accessible at room temperature from the triplet state. The overall triplet decay at a given temperature is dictated by the interplay of these two contributions. This observation bears significance in understanding the underlying fast relaxation processes in Ni-based molecules and related transition metal complexes, opening avenues for potential applications for energy harvesting and optoelectronics.

The discovery of singlet-triplet (ST) inversion in some π-conjugated triangle-shaped boron carbon nitrides is a remarkable breakthrough that defies Hund's first rule. Deeply rooted in strong electron-electron interactions, ST inversion has garnered significant interest due to its potential to revolutionize triplet harvesting in organic LEDs. Using the well-established Pariser-Parr-Pople model for correlated electrons in π-conjugated systems, we employ a combination of CISDT and restricted active space configuration interaction calculations to investigate the photophysics of several triangular boron carbon nitrides. Our findings reveal that ST inversion in these systems is primarily driven by a network of alternating electron-donor and electron-acceptor groups in the molecular rim, rather than by the triangular molecular structure itself.

We present the first microscopic model for the chirality-induced spin selectivity effect in electron-transfer, in which the internal degrees of freedom of the chiral bridge are explicitly included. By exactly solving this model on short chiral chains we demonstrate that a sizable spin polarization on the acceptor arises from the interplay of coherent and incoherent dynamics, with strong electron-electron correlations yielding many-body states on the bridge as crucial ingredients. Moreover, we include the coherent and incoherent dynamics induced by interactions with vibrational modes and show that they can play an important role in determining the long-time polarized state probed in experiments.

Emerging drug candidates more often fall in the beyond-rule-of-five chemical space. Among them, proteolysis targeting chimeras (PROTACs) have gained great attention in the past decade. Although physicochemical properties of small molecules accomplishing Lipinski's rule-of-five can now be easily predicted through models generated by large data collections, for PROTACs the knowledge is still limited and heterogeneous, hampering their prediction. Here, the kinetic solubility and the coefficient of distribution at pH 7.4 (LogD 7.4 ) of 44 PROTACs, designed and synthesized to cover a wide chemical space, were measured. Their generally low solubility and high lipophilicity required an optimization of the experimental methods. Concerning the LogD 7.4 , several in silico prediction tools were tested, which were quite accurate for classical small molecules but provided dissimilar outcomes for PROTACs. Finally, in silico models for the prediction of PROTACs' kinetic solubility and LogD 7.4 were proposed by combining in-house generated experimental data with 3D description of PROTACs' structures.

Pyridine nucleotide-disulfide oxidoreductases are underexplored as drug targets, and thioredoxin reductases (TrxRs) stand out as compelling pharmacological targets. Selective TrxR inhibition is challenging primarily due to the reliance on covalent inhibition strategies. Recent studies identified a regulatory and druggable pocket in Schistosoma mansoni thioredoxin glutathione reductase (TGR), a TrxR-like enzyme, and an established drug target for schistosomiasis. This site is termed the "doorstop pocket" because compounds that bind there impede the movement of an aromatic side-chain necessary for the entry and exit of NADPH and NADP + during enzymatic turnover. This discovery spearheaded the development of new TGR inhibitors with efficacies surpassing those of current schistosomiasis treatment. Targeting the "doorstop pocket" is a promising strategy, as the pocket is present in all members of the pyridine nucleotide-disulfide oxidoreductase family, opening new avenues for exploring therapeutic approaches in diseases where the importance of these enzymes is established, including cancer and inflammatory and infectious diseases.

Deep eutectic solvents (DESs) have attracted increasing attention in recent years due to their broad applicability in different fields, but their computer-aided discovery, which avoids a time-consuming trial-and-error investigation, is still lagging. In this paper, a set of nine DESs, composed of choline chloride as a hydrogen-bond acceptor and nine functionalized phenols as hydrogen bond donors, is simulated by using classical molecular dynamics to investigate the possible formation of a DES. The tool of the Voronoi tessellation analysis is employed for producing an intuitive and straightforward representation of the degree of mixing between the different components of the solutions, therefore permitting the definition of a metric quantifying the propensity of the components to produce a uniform solution. The computational findings agree with the experimental results, thus confirming that the Voronoi tessellation analysis can act as a lightweight yet powerful approach for the high-throughput screening of mixtures in the optics of the new DES design.

Alkyne-functionalized oxetanes are presented as versatile substrates that in combination with amine reagents can be transformed into structurally diverse, chiral γ-amino alcohols featuring a tetrasubstituted tertiary stereocenter under Cu catalysis. Control experiments demonstrate the privileged nature of these oxetane precursors in terms of yield and asymmetric induction levels in the developed protocol, and postsynthetic modifications offer an easy way to access more advanced synthons.

Aqueous ionic solutions are pivotal in various scientific domains due to their natural prevalence and vital roles in biological and chemical processes. Molecular dynamics has emerged as an effective methodology for studying the dynamic behavior of these systems. While all-atomistic models have made significant strides in accurately representing and simulating these ions, the challenge persists in achieving precise models for coarse-grained (CG) simulations. Our study introduces two optimized models for sodium and chloride ions within the nonpolarizable surface property fitting coarse-grained force field (SPICA-FF) framework. The two models represent solvated ions, such as the original FF model, and unsolvated or bare ions. The nonbonded Lennard-Jones interactions were reparameterized to faithfully reproduce bulk properties, including density and surface tension, in sodium chloride solutions at varying concentrations. Notably, these optimized models replicate experimental surface tensions at high ionic strengths, a property not well-captured by the ions of the original model in the SPICA-FF. The optimized unsolvated model also proved successful in reproducing experimental osmotic pressure. Additionally, the newly reparameterized ion models capture hydrophobic interactions within sodium chloride solutions and show qualitative agreement when modeling structural changes in phospholipid bilayers, aligning with experimental observations. For aqueous solutions, these optimized models promise a more precise representation of the ion behavior.

In the realm of nanoscience, the dynamic behaviors of liquids at scales beyond the conventional structural relaxation time, τ, unfold a fascinating blend of solid-like characteristics, including the propagation of collective shear waves and the emergence of elasticity. However, in classical bulk liquids, where τ is typically of the order of 1 ps or less, this solid-like behavior remains elusive in the low-frequency region of the density of states ( DOS ). Here, we provide evidence for the emergent solid-like nature of liquids at short distances through inelastic neutron scattering measurements of the low-frequency DOS in liquid water and glycerol confined within graphene oxide membranes. In particular, upon increasing the strength of confinement, we observe a transition from a liquid-like DOS (linear in the frequency ω) to a solid-like behavior (Debye law, ∼ω 2 ) in the range of 1-4 meV. Molecular dynamics simulations confirm these findings and reveal additional solid-like features, including propagating collective shear waves and a reduction in the self-diffusion constant. Finally, we show that the onset of solid-like dynamics is pushed toward low frequency along with the slowing-down of the relaxation processes upon confinement. This nanoconfinement-induced transition, aligning with k-gap theory, underscores the potential of leveraging liquid nanoconfinement in advancing nanoscale science and technology, building more connections between fluid dynamics and materials engineering.

Ullmann coupling is a widely used reaction for the on-surface growth of low-dimensional carbon nanomaterials. The irreversible nature of this reaction prevents the "self-healing" of defects, and a detailed knowledge of its mechanism is therefore essential to enable the growth of extended ordered structures. However, the dynamics of the Ullmann polymerization remain largely unexplored, as coupling events occur on a timescale faster than conventional scanning probe microscopy imaging frequencies. Here, we reveal the dynamics of these surface events using high-speed variable-temperature scanning tunneling microscopy (STM) (10 frames per second). Performing the measurements at the onset reaction temperatures provides an unprecedented description of the evolution of organometallic (OM) and covalent surface species during the Ullmann polymerization of para -dibromobenzene on Cu(110). Our results demonstrate the existence of an intermediate OM phase with Cu adatoms that inhibits the polymerization. These observations now complete the picture of the pathways of on-surface Ullmann polymerization, which includes the complex interplay of the phenylene moieties and metal atoms. Our work demonstrates the unique capability of high-speed STM to capture the dynamics of molecular self-assembly and coupling.

Platinum exhibits desirable catalytic properties, but it is scarce and expensive. Optimizing its use in key applications such as emission control catalysis is important to reduce our reliance on such a rare element. Supported Pt nanoparticles (NPs) used in emission control systems deactivate over time because of particle growth in sintering processes. In this work, we shed light on the stability against sintering of Pt NPs supported on and encapsulated in Al 2 O 3 using a combination of nanocrystal catalysts and atomic layer deposition (ALD) techniques. We find that small amounts of alumina overlayers created by ALD on preformed Pt NPs can stabilize supported Pt catalysts, significantly reducing deactivation caused by sintering, as previously observed by others. Combining theoretical and experimental insights, we correlate this behavior to the decreased propensity of oxidized Pt species to undergo Ostwald ripening phenomena because of the physical barrier imposed by the alumina overlayers. Furthermore, we find that highly stable catalysts can present an abundance of under-coordinated Pt sites after restructuring of both Pt particles and alumina overlayers at a high temperature (800 °C) in C 3 H 6 oxidation conditions. The enhanced stability significantly improves the Pt utilization efficiency after accelerated aging treatments, with encapsulated Pt catalysts reaching reaction rates more than two times greater than those of a control supported Pt catalyst.

Black phosphorus (bP) is a crystalline material that can be seen as an ordered stacking of two-dimensional layers, which results in outstanding anisotropic physical properties. The knowledge of its pressure ( P )-temperature ( T ) phase diagram, and in particular, of its melting curve is fundamental for a better understanding of the synthesis and stability conditions of this element. Despite the numerous studies devoted to this subject, significant uncertainties remain regarding the determination of the position and slope of its melting curve. Here we measured the melting curve of bP in an extended P , T region from 0.10(3) to 5.05(40) GPa and from 914(25) to 1788(70) K, using in situ high-pressure and high-temperature synchrotron X-ray diffraction. We employed an original metrology based on the anisotropic thermoelastic properties of bP to accurately determine P and T . We observed a monotonic increase of the melting temperature with pressure and the existence of two distinct linear regimes below and above 1.35(15) GPa, with respective slopes of 348 ± 21 and of 105 ± 12 K·GPa -1 . These correspond to the melting of bP toward the low-density liquid and the high-density liquid, respectively. The triple point at which solid bP and the two liquids meet is located at 1.35(15) GPa and 1350(25) K. In addition, we have characterized the solid phases after crystallization of the two liquids and found that, while the high-density liquid transforms back to solid bP, the low-density liquid crystallizes into a more complex, partly crystalline and partly amorphous solid. The X-ray diffraction pattern of the crystalline component could be indexed as a mixture of red and violet P.

X-ray absorption near-edge structure (XANES) spectroscopy has been used, in conjunction with extended X-ray absorption fine structure (EXAFS), to determine the coordination structure of the Ag + ion in a dimethyl sulfoxide (DMSO) solution. From the EXAFS data analysis, the Ag-O first shell distance in DMSO was found to be 2.31(3) Å, with 4.1(5) oxygen atoms surrounding the Ag + ion, in fair agreement with previous results. This technique did not allow us to determine the geometry of the 4-fold coordination complex and a quantitative analysis of the XANES region was carried out to shed light on this issue. The XANES data analysis confirmed the presence of a four-coordinated complex, unambiguously showing that a regular tetrahedral [Ag(DMSO) 4 ] + complex is formed when silver triflate is dissolved in DMSO solution.

In this study, we synthesized novel Pd(II)-indenyl complexes using various N -heterocyclic carbene (NHC) ligands, including chelating NHC-picolyl, NHC-thioether, and diNHC ligands, and two monodentate NHCs. Transmetalation reactions between a Pd(II)-indenyl precursor and silver-NHC complexes were generally employed, except for chelating diNHC derivatives, which required direct reaction with bisimidazolium salts and potassium carbonate. Characterization included NMR, HRMS analysis, and single-crystal X-ray diffraction. In vitro on five ovarian cancer cell lines showed notable cytotoxicity, with IC 50 values in the micro- and submicromolar range. Some compounds exhibited intriguing selectivity for cancer cells due to higher tumor cell uptake. Mechanistic studies revealed that monodentate NHCs induced mitochondrial damage while chelating ligands caused DNA damage. One chelating NHC-picolyl ligand showed promising cytotoxicity and selectivity in high-grade serous ovarian cancer models, supporting its consideration for preclinical study.

G-Quadruplexes (G4s) are appealing targets for anticancer therapy because of their location in the genome and their role in regulating physiological and pathological processes. In this article, we report the characterization of the molecular interaction and selectivity of OAF89, a 9,10-disubstituted G4-binding anthracene derivative, with different DNA sequences. Advanced analytical methods, including mass spectrometry and nuclear magnetic resonance, were used to conduct the investigation, together with the use of in silico docking and molecular dynamics. Eventually, the compound was tested in vitro to assess its bioactivity against lung cancer cell lines., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Magnetic materials are widely used for many technologies in energy, health, transportation, computation, and data storage. For the latter, the readout of the magnetic state of a medium is crucial. Optical readout based on the magneto-optical Faraday effect was commercialized but soon abandoned because of the need for a complex circular polarization-sensitive readout. Combining chirality with magnetism can remove this obstacle, as chiral magnetic materials exhibit magneto-chiral dichroism, a differential absorption of unpolarized light dependent on their magnetic state. Molecular chemistry allows the rational introduction of chirality into single-molecule magnets (SMMs), ultimate nanoobjects capable of retaining magnetization. Here, we report the first experimental demonstration of optical detection of the magnetic state of an SMM using unpolarized light on a novel air-stable Dy-based chiral SMM featuring a strong single-ion magnetic anisotropy. These findings might represent a paradigm shift in the field of optical data readout technologies.

We present a nonlinear spectroelectrochemical technique to investigate photosynthetic protein complexes. The PEC2DES setup combines photoelectrochemical detection (PEC) that selectively probes the protein photogenerated charges output with two-dimensional electronic spectroscopy (2DES) excitation that spreads the nonlinear optical response of the system in an excitation-detection map. PEC allows us to distinguish the contribution of charge separation (CS) from other de-excitation pathways, whereas 2DES allows us to disentangle congested spectral bands and evaluate the exciton dynamics (decays and coherences) of the photosystem complex. We have developed in operando phase-modulated 2DES by measuring the photoelectrochemical reaction rate in a biohybrid electrode functionalized with a plant photosystem complex I-light harvesting complex I (PSI-LHCI) layer. Optimizing the photoelectrochemical current signal yields reliable linear spectra unequivocally associated with PSI-LHCI. The 2DES signal is validated by nonlinear features like the characteristic vibrational coherence at 750 cm -1 . However, no energy transfer dynamics is observed within the 450 fs experimental window. These intriguing results are discussed in the context of incoherent mixing resulting in reduced nonlinear contrast for multichromophoric complexes, such as the 160 chlorophyll PSI. The presented PEC2DES method identifies generated charges unlike purely optical 2DES and opens the way to probe the CS channel in multichromophoric complexes.

The wide variation of nanomaterial (NM) characters (size, shape, and properties) and the related impacts on living organisms make it virtually impossible to assess their safety; the need for modeling has been urged for long. We here investigate the custom-designed 1-10% Fe-doped CuO NM library. Effects were assessed using the soil ecotoxicology model Enchytraeus crypticus (Oligochaeta) in the standard 21 days plus its extension (49 days). Results showed that 10%Fe-CuO was the most toxic (21 days reproduction EC50 = 650 mg NM/kg soil) and Fe 3 O 4 NM was the least toxic (no effects up to 3200 mg NM/kg soil). All other NMs caused similar effects to E. crypticus (21 days reproduction EC50 ranging from 875 to 1923 mg NM/kg soil, with overlapping confidence intervals). Aiming to identify the key NM characteristics responsible for the toxicity, machine learning (ML) modeling was used to analyze the large data set [9 NMs, 68 descriptors, 6 concentrations, 2 exposure times (21 and 49 days), 2 endpoints (survival and reproduction)]. ML allowed us to separate experimental related parameters (e.g., zeta potential) from particle-specific descriptors (e.g., force vectors) for the best identification of important descriptors. We observed that concentration-dependent descriptors (environmental parameters, e.g., zeta potential) were the most important under standard test duration (21 day) but not for longer exposure (closer representation of real-world conditions). In the longer exposure (49 days), the particle-specific descriptors were more important than the concentration-dependent parameters. The longer-term exposure showed that the steepness of the concentration-response decreased with an increased Fe content in the NMs. Longer-term exposure should be a requirement in the hazard assessment of NMs in addition to the standard in OECD guidelines for chemicals. The progress toward ML analysis is desirable given its need for such large data sets and significant power to link NM descriptors to effects in animals. This is beyond the current univariate and concentration-response modeling analysis.

Antibiotic resistance, particularly among Gram-negative bacteria, poses a significant healthcare challenge due to their ability to evade antibiotic action through various mechanisms. In this study, we explore the prediction of small molecule accumulation in Gram-negative bacteria by using machine learning techniques enhanced with statistical descriptors derived from molecular dynamics simulations. We begin by identifying a minimal set of molecular descriptors that maximize the model's predictive power while preserving human interpretability. We optimize model accuracy, precision, and the area under the receiver operating characteristic curve through an iterative process. We demonstrate that the inclusion of statistical descriptors significantly improves model performance across various prediction metrics. Particularly, the addition of statistical descriptors related to dipole moment and minimum projection radius enhances the model's predictive capabilities, shedding light on the physicochemical properties crucial for small molecule accumulation. Our findings highlight the importance of considering statistical moments beyond mean values in predictive modeling and suggest avenues for future research. Overall, our study provides insights into the complex dynamics of antibiotic accumulation in Escherichia coli bacterial cells, generalizable to other Gram-negative species, offering a promising approach for the discovery of effective antibacterial agents, identifying new hits, and improving them to define effective lead agents.

Polydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), to promote homotypic targeting toward cancer cells. The selective targeting ability and the combined photothermal and chemotherapeutic activity of the CM-SRF-PDA NPs following NIR irradiation have been evaluated on cell cultures in static and dynamic conditions, besides three-dimensional culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex ovo on HepG2 spheroid-grafted quail embryos. This comprehensive investigation, supported by proteomic analysis, showed the effectiveness of the proposed nanoplatform and strongly suggests further pre-clinical testing in the treatment of liver cancer.

Limonene undergoes a regioselective Pd(II)-catalyzed C(sp 2 )-H/C(sp 2 )-H coupling with acrylic acid esters and amides, α,β-unsaturated ketones, styrenes, and allyl acetate, affording novel 1,3-dienes. DFT computations gave results in accord with the experimental results and allowed for the formulation of a plausible mechanism. The postfunctionalization of one of the coupled products was achieved via a large-scale Sonogashira reaction conducted under micellar catalysis.

Recently we investigated from first-principles screening properties in systems where small molecules, characterized by a finite electronic dipole moment, are encapsulated in different nanocages. The most relevant result was the observation of an antiscreening effect in alkali-halide nanocages characterized by ionic bonds: in fact, due to the relative displacement of positive and negative ions, induced by the dipole moment of the encapsulated molecule, these cages act as dipole-field amplifiers, different from what is observed in carbon fullerene nanocages, which exhibit instead a pronounced screening effect. Here we extend the study to another class of nanostructures: the nanotubes. Using first-principles techniques based on density functional theory, we studied the properties of endohedral nanotubes obtained by encapsulation of a water molecule or a linear HF molecule. A detailed analysis of the effective dipole moment of the complexes and of the electronic charge distribution suggests that screening effects crucially depend not only on the nature of the intramolecular bonds but also on the size and the shape of the nanotubes and on the specific encapsulated molecule. As observed in endohedral nanocages, screening is maximum in covalent-bond carbon nanotubes, while it is reduced in partially ionic nanotubes, and an antiscreening effect is observed in some ionic nanotubes. However, in this case, the scenario is more complex than in corresponding ionic nanocages. In fact the specific geometric structure of alkali-halide nanotubes turns out to be crucial for determining the screening/antiscreening behavior: while nanotubes with octagonal transversal section can exhibit an antiscreening effect, which quantitatively depends on the number of layers in the longitudinal direction, instead nanotubes with dodecagonal section are always characterized by a reduction of the total dipole moment so that a screening behavior is observed. Our results show that, even in nanotube structures, in principle one can tune the dipole moment and generate electrostatic fields at the nanoscale without the aid of external potentials.

In recent years, hydrogen has gained attention as a potential solution to replace fossil fuels, thus reducing greenhouse gas emissions. The development of ever improving hydrogen sensors is a topic that is constantly under study due to concerns about the inherent risk of leaks of this gas and potential explosions. In this work, a new, long-term, stable phosphorene-based sensor was developed for hydrogen detection. A simple functionalization of phosphorene using urea was employed to synthesize an air-stable material, subsequently used to prepare films for gas sensing applications, via the drop casting method. The material was deeply characterized by different techniques (scanning electron microscopy, X-ray diffraction, X-ray photoelectron, and Raman spectroscopy), and the stability of the material in a noninert atmosphere was evaluated. The phosphorene-based sensor exhibited high sensitivity (up to 700 ppm) and selectivity toward hydrogen at room temperature, as well as long-term stability over five months under ambient conditions. To gain further insight into the gas sensing mechanism over the surface, we employed a dedicated apparatus, namely operando diffuse reflectance infrared Fourier transform, by exposing the chemoresistive sensor to hydrogen gas under dry air conditions.

Fluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several agents have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become the standard of care in cancer surgeries. One of the key parameters to optimize in contrast agents is molecular size, which dictates much of the pharmacokinetic and pharmacodynamic properties of the agent. Here, we describe the development of a class of protease-activated quenched fluorescent probes in which a N -(2-hydroxypropyl)methacrylamide copolymer is used as the primary scaffold. This copolymer core provides a high degree of probe modularity to generate structures that cannot be achieved with small molecules and peptide probes. We used a previously validated cathepsin substrate and evaluated the effects of length and type of linker, as well as the positioning of the fluorophore/quencher pair on the polymer core. We found that the polymeric probes could be optimized to achieve increased overall signal and tumor-to-background ratios compared to the reference small molecule probe. Our results also revealed multiple structure-activity relationship trends that can be used to design and optimize future optical imaging probes. Furthermore, they confirm that a hydrophilic polymer is an ideal scaffold for use in optical imaging contrast probes, allowing a highly modular design that enables efficient optimization to maximize probe accumulation and overall biodistribution properties.

A 3 adenosine receptor (A 3 AR) positive allosteric modulators (PAMs) (2,4-disubstituted-1 H -imidazo[4,5- c ]quinolin-4-amines) allosterically increase the E max of A 3 AR agonists, but not potency, due to concurrent orthosteric antagonism. Following mutagenesis/homology modeling of the proposed lipid-exposed allosteric binding site on the cytosolic side, we functionalized the scaffold, including heteroatom substitutions and exocyclic phenylamine extensions, to increase allosteric binding. Strategically appended linear alkyl-alkynyl chains with terminal amino/guanidino groups improved allosteric effects at both human and mouse A 3 ARs. The chain length, functionality, and attachment position were varied to modulate A 3 AR PAM activity. For example, 26 (MRS8247, p -alkyne-linked 8 methylenes) and homologues increased agonist Cl-IB-MECA's E max and potency ([ 35 S]GTPγS binding). The putative mechanism involves a flexible, terminally cationic chain penetrating the lipid environment for stable electrostatic anchoring to cytosolic phospholipid head groups, suggesting "lipid trolling", supported by molecular dynamic simulation of the active-state model. Thus, we have improved A 3 AR PAM activity through rational design based on an extrahelical, lipidic binding site.

Bimetallic alloys made from immiscible elements are characterized by their tendency to segregate on the macroscopic scale, but their behavior is known to change at the nanoscale. Here, we demonstrate that in the Ru-In system, In atoms preferentially decorate the surface of 6 nm Ru nanoparticles, forming Ru-In superficial immiscible alloys. This surface decoration dramatically affects the catalytic performance of the system, even at small atomic fractions of In added to Ru. The interfaces between Ru and In enabled unexplored methanol productivity from CO 2 hydrogenation, which outperformed not only the individual constituents but also ordered RuIn 3 intermetallic alloys. Our work highlights that the formation of superficial immiscible alloys could offer new insights into the understanding and design of heterogeneous catalysts.