Nearby Molecules Research Articles

Multiomic characterization of RNA microenvironments by oligonucleotide-mediated proximity-interactome mapping.

RNA molecules form complex networks of molecular interactions that are central to their function and to cellular architecture. But these interaction networks are difficult to probe in situ. Here, we introduce Oligonucleotide-mediated proximity-interactome MAPping (O-MAP), a method for elucidating the biomolecules near an RNA of interest, within its native context. O-MAP uses RNA-fluorescence in situ hybridization-like oligonucleotide probes to deliver proximity-biotinylating enzymes to a target RNA in situ, enabling nearby molecules to be enriched by streptavidin pulldown. This induces exceptionally precise biotinylation that can be easily optimized and ported to new targets or sample types. Using the noncoding RNAs 47S, 7SK and Xist as models, we develop O-MAP workflows for discovering RNA-proximal proteins, transcripts and genomic loci, yielding a multiomic characterization of these RNAs' subcellular compartments and new regulatory interactions. O-MAP requires no genetic manipulation, uses exclusively off-the-shelf parts and requires orders of magnitude fewer cells than established methods, making it accessible to most laboratories.

Stabilizing zinc anodes by a solvation sheath modification with toluenesulfonate additive

As an advanced electrochemical energy storage device, aqueous zinc-ion batteries offer high theoretical capacity and energy density, employing water-based electrolytes to reduce fire and explosion risks. However, zinc tends to form dendrites during charge-discharge processes, leading to reduced electrode surface area and shortened cycling lifespan. In this study, we propose the use of a commonly used and cost-effective additive, sodium p-toluenesulfonate (OTM), to stabilize zinc anodes. Experimental and theoretical simulations demonstrate that OTM can enter the solvation sheath of Zn2+, reduce the activity of nearby H2O molecules, facilitate uniform Zn2+ deposition, and suppress zinc dendrite formation. Therefore, Zn//Zn symmetric batteries utilizing ZnSO4 (ZSO) electrolytes containing OTM achieved outstanding long-term performance exceeding 1700 h at 1 mA cm−2, significantly surpassing those employing ZSO electrolytes. Additionally, Zn//VO2 full batteries with OTM additives exhibited enhanced cycling stability and an initial discharge capacity of 180 mAh g−1 at 3 A g−1, demonstrating its superior application potential.

Strong coupling induced ultrasensitive chiral detection by metal-dielectric hybrid metasurface

Circular dichroism (CD) spectroscopy struggles to detect weak signals from small, chiral molecules due to limitations in light absorption. This study introduces a method for significantly enhancing CD signals using a metal-dielectric hybrid metasurface. The metasurface creates a superchiral hotspot that amplifies the chirality of nearby molecules. Two techniques are proposed to overcome signal cancellation between the intrinsic and induced signals to achieve an overall enhancement of the CD signal by up to 23,630 times. This approach has the potential for ultrasensitive detection of chiral molecules at the nanoscale, with applications in pharmacology, toxicology, and life sciences.

A Review on Recent Trends in Photo-Drug Efficiency of Advanced Biomaterials in Photodynamic Therapy of Cancer.

Photodynamic Therapy (PDT) has emerged as a highly efficient and non-invasive cancer treatment, which is crucial considering the significant global mortality rates associated with cancer. The effectiveness of PDT primarily relies on the quality of the photosensitizers employed. When exposed to appropriate light irradiation, these photosensitizers absorb energy and transition to an excited state, eventually transferring energy to nearby molecules and generating Reactive Oxygen Species (ROS), including singlet oxygen [1O2]. The ability to absorb light in visible and nearinfrared wavelengths makes porphyrins and derivatives useful photosensitizers for PDT. Chemically, Porphyrins, composed of tetra-pyrrole structures connected by four methylene groups, represent the typical photosensitizers. The limited water solubility and bio-stability of porphyrin photosensitizers and their non-specific tumor-targeting properties hinder PDT effectiveness and clinical applications. Therefore, a wide range of modification and functionalization techniques have been used to maximize PDT efficiency and develop multidimensional porphyrin-based functional materials. Recent progress in porphyrin-based functional materials has been investigated in this review paper, focusing on two main aspects including the development of porphyrinic amphiphiles that improve water solubility and biocompatibility, and the design of porphyrin-based polymers, including block copolymers with covalent bonds and supramolecular polymers with noncovalent bonds, which provide versatile platforms for PDT applications. The development of porphyrin-based functional materials will allow researchers to significantly expand PDT applications for cancer therapy by opening up new opportunities. With these innovations, porphyrins will overcome their limitations and push PDT to the forefront of cancer treatment options.

Bringing Molecules Together: Synergistic Coadsorption at Dopant Sites of Single Atom Alloys.

Bringing molecules together on a catalytic surface is a prerequisite for bimolecular and recombination reactions. However, in the absence of attractive interactions between reactants, such as hydrogen bonds, this poses a challenge. In contrast, based on density functional theory, we show that coadsorption at active sites of single-atom alloys (SAAs) is favored and that coadsorption is a general phenomenon observed for catalytically relevant adsorbates on a broad range of SAAs under temperature and pressure conditions commonly employed for catalysis. Dopants located in both terrace sites and in step edge defects exhibit a preference for coadsorption, displaying similar periodic trends. Using kinetic Monte Carlo simulations, we compare the reactivity of a model reaction on both a pure metal and an SAA and show that the preference for coadsorption significantly alters the overall reaction energy profile, even when the barriers for the rate-determining elementary step are identical. In our models, the coadsorption preference enhances the catalytic activity of the SAA surface by several orders of magnitude compared to the pure metal. We also report infrared (IR) spectroscopic signatures of coadsorption, which facilitate experimental detection. Analysis reveals that in these systems repulsive lateral interactions between nearby molecules are more than compensated for by the enhanced binding at dopant sites. Among the broad range of systems considered, SAAs containing early transition metals (TMs) exhibit the strongest coadsorption preference, which can be rationalized by assuming the existence of an optimal number of electrons involved in binding. The strong coadsorption preference, together with facile product desorption from early TMs, renders these systems attractive candidates for catalysis. Moreover, these SAAs could open new routes for reduction reactions because coadsorption with hydrogen is favored.

Controlling Plasmonic Catalysis via Strong Coupling with Electromagnetic Resonators.

Plasmonic excitations decay within femtoseconds, leaving nonthermal (often referred to as "hot") charge carriers behind that can be injected into molecular structures to trigger chemical reactions that are otherwise out of reach─a process known as plasmonic catalysis. In this Letter, we demonstrate that strong coupling between resonator structures and plasmonic nanoparticles can be used to control the spectral overlap between the plasmonic excitation energy and the charge injection energy into nearby molecules. Our atomistic description couples real-time density-functional theory self-consistently to an electromagnetic resonator structure via the radiation-reaction potential. Control over the resonator provides then an additional knob for nonintrusively enhancing plasmonic catalysis, here more than 6-fold, and dynamically reacting to deterioration of the catalyst─a new facet of modern catalysis.

Ab Initio Simulation of Liquid Water without Artificial High Temperature.

Comprehending the structure and dynamics of water is crucial in various fields, such as water desalination, ion separation, electrocatalysis, and biochemical processes. While reported works show that the ab initio molecular dynamics (AIMD) can accurately portray water's structure, the artificial high temperature (AHT) from 120 to 30 K is needed to mimic the quantum nature of hydrogen-bond network from GGA, metaGGA to hybrid functionals. The AHT proves to be an inadequate approach for systems involving aqueous multiphase mixtures, such as water-solid interfaces and aqueous solutions. This is due to the activation of additional phonons in other phases, which can lead to an overestimation of the dynamics of nearby water molecules. In this work, we find that the regularized SCAN (rSCAN) functional effectively captures both the structure and dynamics of liquid water at ambient conditions without AHT. Moreover, rSCAN closely matches experimental results for the hydration structures of alkali, alkali earth, and halide ions. We anticipate that the versatile and accurate rSCAN functional will emerge as a key tool based on ab initio simulation for investigating chemical processes in aqueous environments.

Mechanism for the synergistic gelation of konjac glucomannan and κ-carrageenan

The synergistic interaction gels (SIGs) can be created by blending konjac glucomannan (KGM) and κ-carrageenan, and have been applied to modify and improve the rheological and texture properties of food system. However, the assembly behaviors between them are still unclear. This work revealed that the presence of KGM promoted phase transition of nearby κ-carrageenan molecules probably by contributing to entropy increment. Subsequently, the rest of κ-carrageenan transformed into helical structure, assembled into a series of laterally arranged trigonal units and formed a three-dimensional network. In KGM/κ-carrageenan SIGs, the size of high density domains (Ξ) in aggregates and the distance of these high density domains (ξ) were narrowed firstly and then enlarged as increasing of KGM content. These nano-scale structure features were responsible for the relative higher gel strength for KGM/κ-carrageenan SIGs with proportion ratios of 1:9 (K1C9) and 3:7 (K3C7). This study serves to facilitate the design and production of SIGs with the requisite performance characteristics.

Transcriptome-Wide, Unbiased Profiling of Ribonuclease Targeting Chimeras.

Various approaches have been developed to target RNA and modulate its function with modes of action including binding and cleavage. Herein, we explored how small molecule binding is correlated with cleavage induced by heterobifunctional ribonuclease targeting chimeras (RiboTACs), where RNase L is recruited to cleave the bound RNA target, in a transcriptome-wide, unbiased fashion. Only a fraction of bound targets was cleaved by RNase L, induced by RiboTAC binding. Global analysis suggested that (i) cleaved targets generally form a region of stable structure that encompasses the small molecule binding site; (ii) cleaved targets have preferred RNase L cleavage sites nearby small molecule binding sites; (iii) RiboTACs facilitate a cellular interaction between cleaved targets and RNase L; and (iv) the expression level of the target influences the extent of cleavage observed. In one example, we converted a binder of LGALS1 (galectin-1) mRNA into a RiboTAC. In MDA-MB-231 cells, the binder had no effect on galectin-1 protein levels, while the RiboTAC cleaved LGALS1 mRNA, reduced galectin-1 protein abundance, and affected galectin-1-associated oncogenic cellular phenotypes. Using LGALS1, we further assessed additional factors including the length of the linker that tethers the two components of the RiboTAC, cellular uptake, and the RNase L-recruiting module on RiboTAC potency. Collectively, these studies may facilitate triangulation of factors to enable the design of RiboTACs.

The co-promoting mechanism of EMEA/DEEA/PZ ternary water-lean solvent on CO2 capture- a study based on 13C-qNMR and DFT calculations

Amine based CO2 absorption is currently the most promising means of capturing CO2 in industry, and the water-lean amine solvent has received widespread attentions. The reaction mechanism of the EMEA/DEEA/PZ ternary water-lean amine solvent (WLS) during the process of CO2 capture was investigated theoretically to understand the synergistic effect between the different amine components. The concentrations of intermediate products were analyzed by 13C-qNMR (quantitative Nuclear Magnetic Resonance) spectroscopy, while the reaction mechanisms were calculated using gaussian 16. The NMR results showed that carbamate (EMEACOO-), HCO3–/CO32– were the main products in the carbon capture process of EMEA WLS. The protonated amine concentration varies according to the change of carbon dioxide concentration. The balance between deprotonation (forming carbamates) and CO2 removal (regenerating EMEA) depends largely on how ampholytes interact with nearby water molecules. The DFT result showed that EMEA is the key component of CO2 capture, while DEEA and PZ primarily assist in transferring protons, catalyzing the conversion of H2CO3 into HCO3– to accelerate the process of CO2 capture. Furthermore, they assist in the redaction of EMEAH+ to EMEA, allowing it continue to participate in capture reactions. DEEA, PZ and water could promote activating the protonated EMEA and enhanced its capacity of CO2 capture. Furthermore, the desorption process confirmed the proton transfer from DEEAH+, ultimately leading to the regeneration of EMEA, thereby demonstrating the effective performance of regeneration.

A Molecular Dynamics Simulation Study of the Effects of βGln114 Mutation on the Dynamic Behavior of the Catalytic Site of the Tryptophan Synthase.

L-tryptophan (l-Trp), a vital amino acid for the survival of various organisms, is synthesized by the enzyme tryptophan synthase (TS) in organisms such as eubacteria, archaebacteria, protista, fungi, and plantae. TS, a pyridoxal 5'-phosphate (PLP)-dependent enzyme, comprises α and β subunits that typically form an α2β2 tetramer. The enzyme's activity is regulated by the conformational switching of its α and β subunits between the open (T state) and closed (R state) conformations. Many microorganisms rely on TS for growth and replication, making the enzyme and the l-Trp biosynthetic pathway potential drug targets. For instance, Mycobacterium tuberculosis, Chlamydiae bacteria, Streptococcus pneumoniae, Francisella tularensis, Salmonella bacteria, and Cryptosporidium parasitic protozoa depend on l-Trp synthesis. Antibiotic-resistant salmonella strains have emerged, underscoring the need for novel drugs targeting the l-Trp biosynthetic pathway, especially for salmonella-related infections. A single amino acid mutation can significantly impact enzyme function, affecting stability, conformational dynamics, and active or allosteric sites. These changes influence interactions, catalytic activity, and protein-ligand/protein-protein interactions. This study focuses on the impact of mutating the βGln114 residue on the catalytic and allosteric sites of TS. Extensive molecular dynamics simulations were conducted on E(PLP), E(AEX1), E(A-A), and E(C3) forms of TS using the WT, βQ114A, and βQ114N versions. The results show that both the βQ114A and βQ114N mutations increase protein backbone root mean square deviation fluctuations, destabilizing all TS forms. Conformational and hydrogen bond analyses suggest the significance of βGln114 drifting away from cofactor/intermediates and forming hydrogen bonds with water molecules necessary for l-Trp biosynthesis. The βQ114A mutation creates a gap between βAla114 and cofactor/intermediates, hindering hydrogen bond formation due to short side chains and disrupting β-sites. Conversely, the βQ114N mutation positions βAsn114 closer to cofactor/intermediates, forming hydrogen bonds with O3 of cofactors/intermediates and nearby water molecules, potentially disrupting the l-Trp biosynthetic mechanism.

Directed ultrafast conformational changes accompany electron transfer in a photolyase as resolved by serial crystallography

Charge-transfer reactions in proteins are important for life, such as in photolyases which repair DNA, but the role of structural dynamics remains unclear. Here, using femtosecond X-ray crystallography, we report the structural changes that take place while electrons transfer along a chain of four conserved tryptophans in the Drosophila melanogaster (6-4) photolyase. At femto- and picosecond delays, photoreduction of the flavin by the first tryptophan causes directed structural responses at a key asparagine, at a conserved salt bridge, and by rearrangements of nearby water molecules. We detect charge-induced structural changes close to the second tryptophan from 1 ps to 20 ps, identifying a nearby methionine as an active participant in the redox chain, and from 20 ps around the fourth tryptophan. The photolyase undergoes highly directed and carefully timed adaptations of its structure. This questions the validity of the linear solvent response approximation in Marcus theory and indicates that evolution has optimized fast protein fluctuations for optimal charge transfer.

Alignment transport between ultracold polar molecules.

We propose an array of ultracold polar molecules as a platform to study alignment transport between molecules. We envision a polar molecule being aligned with an intense off-resonant laser field whose alignment migrates to a nearby molecule due to dipole-dipole interactions. Our results show that the transport of the alignment is due to a complex interplay between electric field-driven excitations and dipole-dipole interactions. All mechanisms for alignment transfer are elucidated and analyzed. Using NaCs as a prototype molecule, we find that the time for alignment transfer is (10 μs), which makes the phenomena readily observable in the lab.

Interaction of Melatonin with Zwitterionic Model Lipid Membranes

Melatonin is a key hormone secreted by the pineal gland in the brain. It interacts strongly with cell membranes and plays a protective role in several diseases such as Alzheimer's disease, cardiovascular diseases, and cancer. Hence, studies on the interaction of melatonin with lipid bilayer membranes have gained importance. In this regard, the present study aims to analyze the influence of different concentrations (0 to 15 mol%) of melatonin on the thermal and structural properties of zwitterionic stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) lipid bilayer model systems by using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The DSC results have shown that melatonin interacts with the membrane in a concentration-dependent fashion, induces patch formation, and alters the phase behaviour by reducing the main phase transition temperature. FTIR data has shown that increasing the melatonin concentration caused a reduction in the wavenumber of C=O and PO$$_{2}^-$$ antisymmetric stretching vibrations corresponding to the ester carbonyl and phosphate groups of SOPC lipids. This indicates the possibility of strong hydrogen bonding of melatonin with the SOPC lipids and nearby water molecules in the environment, suggesting its preferential location near lipid heads at the interfacial region. These results help to understand the organization and interactions of melatonin with membranes and provide insights to develop safe melatonin-based formulations for pharmaceutical applications.

Novel and efficient Bi-doped CoTe nano-solar evaporators embedded on leno weave cotton gauze for efficient solar-driven desalination

Solar-driven desalination is considered an alternative to the conventional desalination due to its nearly zero carbon footprint and ease of operating in remote areas. Water can be purified wherever sunlight is available, providing a viable solution to water shortage. Metal chalcogenide-based materials are revolutionary for solar evaporators due to their excellent photothermal conversion efficiency, facile synthesis methods, stability, and low cost. Herein we present a prototype Bi-doped CoTe nano-solar evaporator embedded on leno weave cotton gauze (Bi/CoTe@CG) using the sonication process. The nano-solar evaporator was synthesized using a simple hydrothermal approach to provide an opportunity to scale up. The as designed solar evaporator consisting of 5 % Bi/CoTe@CG showed an excellent water flux of 2.38 kg m−2 h−1 upon one sun radiation (1 kW m−2), considered among the highest literature-reported values. The introduced solar evaporator showed excellent solar efficiency of 96.7 %, good stability, and reusability for five cycles of one hour. The best doping ratio of Bi in CoTe was obtained as Bi0.5Co9.5Te with a contact angle of 11.9° in powder form. The hydrophilic nature of the designed solar-evaporator increased the water interaction with the embedded nano-solar evaporator, which helps the transfer of the heat to nearby water molecules, break their hydrogen bonding and increase the evaporation rate. The ion concentration, of the desalinated pure water collected using Bi/CoTe@CG, decreased by many orders of magnitude and it is far below the limit of WHO standards for Na+ and K+. Thus, a self-floating Bi-doped CoTe nano-solar evaporator deposited on cotton gauze (CG) is an excellent solar evaporator for seawater desalination. The proposed solar evaporator is another step towards introducing environmentally friendly desalination methods.

Examining Energy Storage Potential in Weakly Polar Nematic Liquid Crystals Infused with Anthraquinone Dye: A Comprehensive Approach

The applications of liquid crystals in the field of renewable, clean and sustainable technologies of energy storage are of utmost importance at present. This paper delves into dielectric spectroscopic studies of a weakly polar nematic liquid crystal (NLC) enriched with an anthraquinone dye. The primary objective is to assess the impact of increasing dye concentrations on various properties. Anthraquinone dye has been found to increase the dielectric permittivity of weakly polar NLC, leading to a 4.7-fold increase in dielectric anisotropy. Simultaneously, a reduction of around 11% in threshold and operating voltages of the NLC has also been recorded after using dye as the guest material. The added dipolar contributions provided by dye molecules have been attributed to this surplus permittivity. The NLC has been found to have an approximately 54% faster response to the applied field. The intrinsic polarization field of dye molecules accelerates nearby LC molecule reorientation, leading to a 56.5% faster fall time and a 29.8% faster rise time in a 3.0 wt% dye-doped LC cell. These experimental results have been validated via computational studies as well. The simulation results about dipole moment and polarizability provide robust support for our experimental results. Such composites evince their potential for energy storage and 5G communication technologies with adjustable impedance and permittivity.

Vibrational Coupling to Quasi‐Bound States in the Continuum under Tailored Coupling Conditions

AbstractPhotonic resonance modes can be spectrally coupled to the vibrational modes of molecules in the mid‐infrared regime through interactions between localized electric fields and nearby molecules. According to recent studies, radiative loss engineering of coupled systems is a promising approach for tailoring coupling conditions and enhancing the molecular signals. However, this strategy has only been realized using the localized surface plasmon resonances of metal nanostructures, which suffer from increased ohmic loss in the mid‐infrared region and face serious limitations in achieving high quality (Q) factors. In this study, silicon‐based metasurfaces formed on silicon‐on‐insulator wafers are adopted to achieve high Q factors and tune the coupling conditions between the quasi‐bound states in the continuum (qBICs) and molecular vibrations. The coupling between the resonance mode and polymethyl methacrylate molecules is tailored from weak to strong coupling regimes by simply changing the structural asymmetry parameter and utilizing the intrinsically high Q factors of the qBIC modes. In addition, the optimal asymmetry parameter that maximizes the enhanced molecular signal is identified, opening a route toward realizing highly sensitive surface‐enhanced infrared spectroscopy using complementary metal–oxide–semiconductor compatible all‐dielectric materials.

Amide isomerization pathways: Electronic and structural background of protonation- and deprotonation-mediated cis-trans interconversions.

The cis-trans isomerization of amide bonds leads to wide range of structural and functional changes in proteins and can easily be the rate-limiting step in folding. The trans isomer is thermodynamically more stable than the cis, nevertheless the cis form can play a role in biopolymers' function. The molecular system of N-methylacetamide · 2H2O is complex enough to reveal energetics of the cis-trans isomerization at coupled cluster single-double and coupled cluster single-double and perturbative triple [CCSD(T)] levels of theory. The cis-trans isomerization cannot be oversimplified by a rotation along ω, since this rotation is coupled with the N-atom pyramidal inversion, requesting the introduction of a second dihedral angle "α." Full f(ω,α) potential energy surfaces of the different amide protonation states, critical points and isomerization reaction paths were determined, and the barriers of the neutral, O-protonated and N-deprotonated amides were found too high to allow cis-trans interconversion at room temperature: ∼85, ∼140, and ∼110 kJ mol-1, respectively. For the N-protonated amide bond, the cis form (ω = 0°) is a maximum rather than a minimum, and each ω state is accessible for less than ∼10 kJ mol-1. Here we outline a cis-trans isomerization pathway with a previously undescribed low energy transition state, which suggests that the proton is transferred from the more favorable O- to the N-protonation site with the aid of nearby water molecules, allowing the trans → cis transition to occur at an energy cost of ≤11.6 kJ mol-1. Our results help to explain why isomerase enzymes operate via protonated amide bonds and how N-protonation of the peptide bond occurs via O-protonation.

(Invited) Cations at a Solid-Liquid Interface: A Second Harmonic Generation Investigation

When an electrode contacts an electrolyte, an interfacial electric field forms. This interfacial field can polarize the electrode’s surface and nearby molecules, but its effect can be reversed by applying external potential. One method for quantifying this effect is the phase-sensitive second harmonic generation (PS-SHG) technique. We present our PS-SHG investigation of the Pt/water interface, where we examine the impact of the electrolyte chemistry on the electrical double layer (EDL). We will discuss how switching cations in alkaline electrolytes can affect the solid-liquid interface, in particular, the behavior of interfacial water. Our work provides a tool for quantifying the interfacial electric field at an electrode-electrolyte interface and shows the possibility of how cations can modify the EDL.

Mapping Atomic-Scale Metal-Molecule Interactions: Salient Feature Extraction through Autoencoding of Vibrational Spectroscopy Data.

Atomic-scale features, such as step edges and adatoms, play key roles in metal-molecule interactions and are critically important in heterogeneous catalysis, molecular electronics, and sensing applications. However, the small size and often transient nature of atomic-scale structures make studying such interactions challenging. Here, by combining single-molecule surface-enhanced Raman spectroscopy with machine learning, spectra are extracted of perturbed molecules, revealing the formation dynamics of adatoms in gold and palladium metal surfaces. This provides unique insight into atomic-scale processes, allowing us to resolve where such metallic protrusions form and how they interact with nearby molecules. Our technique paves the way to tailor metal-molecule interactions on an atomic level and assists in rational heterogeneous catalyst design.