Molecules In Terms Research Articles

Cannabinoids, their cellular receptors, and effects on the invasive phenotype of carcinoma and metastasis.

BackgroundThe morbidity and mortality of cancer are significantly impacted by the invasive and metastatic potential of particular subgroups of malignant cells within a tumor. The particular pre‐metastatic properties of cancerous cells are thus a critical target for novel therapeutics in the oncology field. Cannabinoid molecules have been investigated in recent years in the context of invasion and metastasis of various malignancies, with varying effects reported in the literature.Recent FindingsThere was substantial variability in the findings reported by the literature of the effects of cannabinoid molecules on cancer cell invasion and metastasis. These effects varied depending on which ligand and which of the CB1, CB2, or GPR55 receptors were investigated. These findings suggest a role for the phenomenon of biased signaling in explaining the diversity of effects of cannabinoid molecules on cancer cell invasion.ConclusionWhile substantially more investigation is required into the effects of cannabinoid molecules on cancer cell invasion and metastasis, we describe in this review the significant diversity in the responses of cancer cells to cannabinoid molecules in terms of their invasive and metastatic capacities.

Exploring the Concept of Dimerization-Induced Intersystem Crossing: At the Origins of Spin-Orbit Coupling Selection Rules.

Singlet-triplet interconversions (intersystem crossing, ISC) in organic molecules are at the basis of many important processes in cutting-edge photonic applications (organic light-emitting devices, photodynamic therapy, etc.). Selection rules for these transitions are mainly governed by the spin-orbit coupling (SOC) phenomenon. Although the SOC relies on complex relativistic phenomena, theoreticians have, with time, developed increasingly sophisticated and efficient approaches to gain access to a satisfactory evaluation of its magnitude. However, recent works have highlighted the remarkable and somehow unexpected efficiency of dimers of small conjugated molecules in terms of ISC quantum yields, whose origin has not been completely investigated. In this work, we bring a coupled experimental and theoretical analysis of the origin of the unusually large ISC efficiency on a series of such dimers that differ by their nature (covalent or supramolecular). We show that considering the dynamical nature of the SOC, and especially its dependence on angular orientations between the dimer subunits sometimes overlooked in the literature, it is necessary to rationalize some counterintuitive experimental observations. This combined experimental and theoretical work paves the way for new molecular engineering rules for SOC control.

The importance of sPD-1, sOX40L and sGITR in terms of clinicopathology and histopathology in gastric cancer

Abstract Objectives Immunoregulatory GITR, OX40L and PD-1 molecules play an active role in the regulation of tumor microenvironment and have been shown in many cancer types. However, there are limited studies of these molecules in terms of gastric cancer. In our study, we aimed to determine the histopathological significance of sPD-1, sOX40L and sGITR levels in gastric cancer cases. Methods Serum samples were obtained from peripheral blood samples of 20 gastric cancer and 34 healthy controls and candidate biomarker levels were determined by ELISA. Results sGITR level was found to be 48.28 ± 2.66 pg/mL in the gastric cancers and 39.19 ± 2.01 pg/mL in the controls (p=0.014). sOX40L level was 6.13 ± 0.64 pg/mL in the patients and 8.68 ± 0.99 pg/mL in the control, and the sOX40L level was found to be 1.41 times higher in the control group compared to the patients (p=0.033). sGITR levels of signet-ring cell carcinoma were found to be higher than other adenocarcinomas (p=0.04). There was no difference between groups in sPD-1 (p=0.490). Conclusions We suggest that sGITR, sOX40L and molecules may play a role in tumor microenvironment regulation and histological type in gastric cancer.

Electrostatic Potential Topology for Probing Molecular Structure, Bonding and Reactivity.

Following the pioneering investigations of Bader on the topology of molecular electron density, the topology analysis of its sister field viz. molecular electrostatic potential (MESP) was taken up by the authors’ groups. Through these studies, MESP topology emerged as a powerful tool for exploring molecular bonding and reactivity patterns. The MESP topology features are mapped in terms of its critical points (CPs), such as bond critical points (BCPs), while the minima identify electron-rich locations, such as lone pairs and π-bonds. The gradient paths of MESP vividly bring out the atoms-in-molecule picture of neutral molecules and anions. The MESP-based characterization of a molecule in terms of electron-rich and -deficient regions provides a robust prediction about its interaction with other molecules. This leads to a clear picture of molecular aggregation, hydrogen bonding, lone pair–π interactions, π-conjugation, aromaticity and reaction mechanisms. This review summarizes the contributions of the authors’ groups over the last three decades and those of the other active groups towards understanding chemical bonding, molecular recognition, and reactivity through topology analysis of MESP.

Template-Free Construction of Tin Oxide Porous Hollow Microspheres for Room-Temperature Gas Sensors.

Porous hollow microsphere (PHM) materials represent ideal building blocks for realizing diverse functional applications such as catalysis, energy storage, drug delivery, and chemical sensing. This has stimulated intense efforts to construct metal oxide PHMs for achieving highly sensitive and low-power-consumption semiconductor gas sensors. Conventional methods for constructing PHMs rely on delicate reprogramming of templates and may suffer from the structural collapse issue during the removal of templates. Here, we propose a template-free method for the construction of tin oxide (SnO2) PHMs via the competition between the solvent evaporation rate and the phase separation dynamics of colloidal SnO2 quantum wires. The SnO2 PHMs (typically 3 ± 0.5 μm diameter and approximately 200 nm shell thickness) exhibit desirable structural stability with desirable processing compatibility with various substrates. This enables the realization of NO2 gas sensors having a superior response and recovery process at room temperature. The superior NO2-sensing characteristic is attributed to the effective gas adsorption competition on solid surfaces benefiting from efficient diffusion channels, enhancing the interaction of metal oxide solids with gas molecules in terms of the receptor function, transducer function, and utility factor. In addition, the one-step deposition of SnO2 PHMs directly onto device substrates simplifies the fabrication conditions for semiconductor gas sensors. The desirable structural stability of PHMs combined with the functional diversity of metal oxides may open new opportunities for the design of functional materials and devices.

Investigation of the interactions of cationic guar with human hair by electrokinetic analysis.

ObjectiveCationic guar is an important polysaccharide used as a hair conditioning agent in personal care products. In this article, we report streaming potential data demonstrating its behaviour as it interacts electrostatically with hair. Several cationic guar variants with different molecular weights (MWs) and charge densities (CDs) were examined.MethodsAll experiments were carried out with a custom‐designed streaming potential instrument so that in situ, real‐time data were monitored during the treatment of a hair plug with aqueous solutions of cationic guar and subsequent treatment with anionic surfactants—sodium laureth sulfate (SLES) and cocamidopropyl betaine (CAPB)—commonly found in contemporary shampoo formulations.ResultsThe MW of the cationic guar variants plays an integral role in determining the thickness of the adsorbed polymer layer on the hair surface while CD influences the zeta potential. Data were also generated for the treatment of hair with a cationic flexible polymer (polyquaternium‐28) and cationic conditioning surfactant (behentrimonium chloride) to provide a frame of reference. The deposition behaviour on hair of high MW cationic guar variants is distinct from these conventional molecules in terms of its electrokinetic properties. We also examined the electrokinetic behaviour of cationic guar on hair types from different racial backgrounds. While the cationic guar treatment yielded similar results for the different hair types, anionic surfactant treatment resulted in quicker sorption and desorption from African, European 65% grey, and Mulatto hair as compared to Chinese, European dark brown, and Indian hair.ConclusionWe introduce an in situ technique for measuring the dynamic sorption/desorption of charged molecules on the surface of human hair. Evaluation of a series of cationic guar species revealed varying behaviour depending on the MW and CD of the polysaccharide. Our data also demonstrate differences in the desorption properties of typical shampoo surfactants for hair from diverse racial backgrounds.

Estimation of ground and excited-state dipole moments of three symmetric carbocyanine dyes via the analysis of luminescence properties

The solvatochromic effect of solvents on the absorption and fluorescence spectra of three carbocyanine dyes, namely 1,1′,3,3,3′,3′-hexamethylindocarbocyanine chloride (HIC); 1,1′,3,3,3′,3′-hexamethylindodicarbocyanine iodide (HIDC); and 3,3′-diethyloxadicarbocyanine iodide (DODC), have been investigated. The experimental ground and excited-state dipole moments of the dyes have been estimated via the well-known models by Lippert-Mataga, Bakhshiev, Kawski-Chamma-Viallet, and the Dimroth-Reichardt’s empirical model. The influence of the solvation effect on the luminescence quantum yields was also examined and a strong correlation between the luminescence quantum yield values and the solvent viscosity was established. The fluorescence signal enhancement sensitivities between dyes were compared based on the Förster-Hoffmann equation. DFT and TDDFT calculations at the CAM-B3LYP/6-31G(d,p) level of theory were performed for the analysis of the nature of the electron transitions in absorption and excitation processes. Six phases different in polarity were considered during these computations, namely the gas, toluene, chloroform, acetone, methanol, and water. Transition electron density plots, Mulliken atomic partial charges, and Mayer bond orders were used for the analysis of the redistribution of electron density upon excitation. The specific behavior of the dyes in the glycerol medium was interpreted via the analysis of non-covalent interactions between the dye and glycerol molecules in terms of the reduced density gradient method.

G4 Matters-The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides.

G-quadruplexes (G4s) are non-canonical structures formed by guanine-rich sequences of DNA or RNA that have attracted increased attention as anticancer agents. This systematic study aimed to investigate the anticancer potential of five G4-forming, sequence-related DNA molecules in terms of their thermodynamic and structural properties, biostability and cellular uptake. The antiproliferative studies revealed that less thermodynamically stable G4s with three G-tetrads in the core and longer loops are more predisposed to effectively inhibit cancer cell growth. By contrast, highly structured G4s with an extended core containing four G-tetrads and longer loops are characterized by more efficient cellular uptake and improved biostability. Various analyses have indicated that the G4 structural elements are intrinsic to the biological activity of these molecules. Importantly, the structural requirements are different for efficient cancer cell line inhibition and favorable G4 cellular uptake. Thus, the ultimate antiproliferative potential of G4s is a net result of the specific balance among the structural features that are favorable for efficient uptake and those that increase the inhibitory activity of the studied molecules. Understanding the G4 structural features and their role in the biological activity of G-rich molecules might facilitate the development of novel, more potent G4-based therapeutics with unprecedented anticancer properties.

Hydroxytyrosol as anti-parkinsonian molecule: Assessment using in-silico and MPTP-induced Parkinson’s disease model

3-Hydroxytyrosol (HXT) is a natural polyphenol present in extra virgin olive oil. It is a key component of Mediterranean diet and is known for its strong antioxidant activity. The present study evaluated the potential of HXT as an anti-parkinsonian molecule in terms of its ability to inhibit MAO-B and thereby maintaining dopamine (DA) levels in Parkinson’s disease (PD). In-silico molecular docking study followed by MMGBSA binding free energy calculation revealed that HXT has a strong binding affinity for MAO-B in comparison to MAO-A. Moreover, rasagiline and HXT interacted with the similar binding sites and modes of interactions. Additionally, molecular dynamics simulation studies revealed stable nature of HXT-MAO-B interaction and also provided information about the amino acid residues involved in binding. Moreover, in vitro studies revealed that HXT inhibited MAO-B in human platelets with IC50 value of 7.78 μM. In vivo studies using MPTP-induced mouse model of PD revealed increase in DA levels with concomitant decrease in DA metabolites (DOPAC and HVA) on HXT treatment. Furthermore, MAO-B activity was also inhibited on HXT administration to PD mice. In addition, HXT treatment prevented MPTP-induced loss of DA neurons in substantia nigra and their nerve terminals in the striatum. HXT also attenuated motor impairments in PD mice assessed by catalepsy bar, narrow beam walk and open field tests. Thus, the present findings reveal HXT as a potential inhibitor of MAO-B, which may be used as a lead molecule for the development of therapeutics for PD.

DOM chemodiversity pierced performance of each tandem unit along a full-scale “MBR+NF” process for mature landfill leachate treatment

Mature landfill leachate contains a substantial fraction of recalcitrant dissolved organic matters (DOM) that is a challenging for conventional wastewater treatment that is typically focused on the removal of biodegradable organic matter. “Biological treatment + membrane treatment” has been widely employed to treat complex leachate. However, the performance of each unit based on both conventional bulk indicators and molecular information has not been well understood. Therefore, the fate of DOM chemodiversity along the full-scale treatment process across ten sampling points over three different seasons were analyzed to determine the efficiency of every unit process with the assistance of ultra-performance liquid chromatography coupled with hybrid quadrupole Orbitrap mass spectrometry. Results showed that the process performance, visualized through the molecular signals, were relatively stable in the temporal dimension. The process removed 83.2%-92.2% of DOM molecules in terms of richness, where lignin/carboxyl-rich alicyclic compounds (CRAM)-likes with relatively high saturation was preferentially removed, while newly generated bio-derived N-containing compounds (N/Cwa 0.15-0.17) became resistant. The relationship between conventional bulk physicochemical indicators and molecular indexes suggested that soluble chemical oxygen demand (sCOD) and dissolved organic carbon (DOC) were contributed by the refractory DOM with high weighted average double bond equivalents (DBEwa), which was distributed in the region of O/C 0.2-0.5 and H/C 1.2-1.8. This refractory DOM required ultrafiltration and nanofiltration for removal. DOM molecules were positively correlated with five-day biochemical oxygen demand (BOD5) and revealed that approximately 96.9%-98.4% of the DOM could be removed or transformed in the primary anoxic zone. In addition, the bio-derived aliphatic/proteins, lipids and lignin/CRAM-likes (O/C > 0.2) with condensed aromatization were the sources of dissolved organic nitrogen (DON) and still remained in the final effluent. The present study suggests that the design and operation of the combination process with biological and membrane treatment could be specifically optimized based on the DOM molecular characteristics of the wastewater.

Virtual vibrational spectrometer for sp2 carbon clusters. 1. Polycyclic benzenoid-fused hydrocarbons

A virtual vibrational spectrometer HF-Spectrodyn, based on efficient computational codes and exploring both restricted and unrestricted Hartree-Fock approximations, is proposed to perform computational vibrational spectroscopy of large sp2 carbon clusters. The computational device allows obtaining one-quantum harmonic spectra of IR absorption and Raman scattering of closed-shell and open-shell molecules. The spectrometer facilities are manifested for the sp2 hydrocarbons on the example of polyacenes (naphthalene and pentacene) and polycyclic benzenoid-fused compounds (coronene as well as (5,5) and (9,9) periacenes). The observed trends disclose a new spectrometric approach for the consideration of vibrational spectra of the molecules in terms of standard valence bonds subjected to particular structural and atomic-content affects.

LncRNAs and Available Databases.

Long noncoding RNAs (lncRNAs) are involved in many regulatory mechanisms in practically every step of the RNA cycle, from transcription to RNA stability and translation. They are a highly heterogeneous class of molecules in terms of site of production, interaction networks, and functions. More and more databases are available on the web with the aim to make public information about lncRNA accessible to the scientific community. Here we review the most interesting resources with the purpose to organize a compendium of useful tools to interrogate before studying a lncRNA of interest.

Development of a small-molecule-based activatable photoacoustic probe.

Photoacoustic (PA) imaging is an emerging imaging modality that combines the advantages of optical imaging and ultrasound imaging. In particular, activatable PA probes, which visualize the presence or the activity of target molecules in terms of a change of the PA signal, are useful tools for functional imaging. In this chapter, we describe the development of small-molecule-based activatable PA probes, focusing on the design and synthesis of PA-MMSiNQ, our recently developed activatable PA probe for HOCl. We also describe the protocols used for evaluation of PA-MMSiNQ with a UV-vis spectrometer and a PA imaging microscope.

Simple methods of modification of daunorubicin on the daunosamine nitrogen atom

Modification of daunorubicin on its NH2 moiety is a well-established synthetic approach to obtain novel derivatives of this compound. Moreover, the daunosamine moiety of this antibiotic is considered to be the most sensitive part of a molecule in terms of biological response to chemical transformations. Using simple and effective synthetic techniques, namely, alkylation under phase-transfer catalysis and an amine addition across an activated multiple bond, a series of daunorubicin derivatives retaining the amine functionality have been obtained, which could also be used as potential precursors for further transformations.

Study of graphite optode for characterization of solid heterocyclic nitrogen-rich imidazole, 1, 2, 4-triazole, tetrazole molecules using visible –NIR laser based time domain photoacoustic spectroscopy

The paper reports the role of graphite as an optode for recording of time domain photoacoustic (PA) spectra of some new solid heterocyclic groups nitrogen-rich imidazole, 1,2,4-triazole and tetrazole molecules using 532 nm and 1064 nm wavelengths. The fundamental and second harmonic of 30 ps pulse duration are obtained from Q-switched Nd: YAG laser at 10 Hz repetition rate. The used solid HEMs have very weak absorption in the visible and NIR region. Therefore, these compounds are physically mixed with graphite powder in equal proportion for enhancing the PA signal. The optode works as a receptor of incident visible-NIR radiation and releases thermal signal which is communicated to reporter explosive molecules in terms of phonon waves and helps to generate acoustic signature. The study also carried out to understand the behavior of acoustic waves with respect to data acquisition time and incident laser energy. These compounds have different non-radiative decay times and quality factors “Q” of PA cavity, which reveals the change in the structure and conjugate bonds of the molecules in the graphite matrix. The finding is also supported by the Raman spectra due to direct coupling of phonon wave’s momentum between graphite and HEMs in terms of shift in the G and D bands of graphite.

Computational evaluation on molecular stability, reactivity, and drug potential of frovatriptan from DFT and molecular docking approach

Molecular stability, fundamental chemical reactive sites, global reactivity descriptors in frovatriptan molecule have been investigated by using computational evaluation and molecular docking approach. The density functional theory has been employed with standard functional B3LYP/6–311++G(d,p). The possible minimum energy structure has been predicted by implementing one-dimensional potential energy surface (PES) scan. The charge delocalization for stability of the molecule with natural bond orbital (NBO) analysis and molecular electrostatic potential (MEP) surface analysis to observe the active region for further chemical reaction with surrounding species have been performed. The chemical reactivity and hardness of the molecule in terms of HOMO-LUMO energy gap (ΔEL-H) have been implemented in terms of reactivity parameters. The potential use of frovatriptan as non-linear optical (NLO) material and its thermodynamical studies have also been performed. Moreover, the molecular docking with a predicted target has been performed to check the binding interaction as well as sites of the molecule.

Unravelling molecular interactions in uracil clusters by XPS measurements assisted by ab initio and tight-binding simulations

The C, N and O 1s XPS spectra of uracil clusters in the gas phase have been measured. A new bottom-up approach, which relies on computational simulations starting from the crystallographic structure of uracil, has been adopted to interpret the measured spectra. This approach sheds light on the different molecular interactions (H-bond, π-stacking, dispersion interactions) at work in the cluster and provides a good understanding of the observed XPS chemical shifts with respect to the isolated molecule in terms of intramolecular and intermolecular screening occurring after the core–hole ionization. The proposed bottom-up approach, reasonably expensive in terms of computational resources, has been validated by finite-temperature molecular dynamics simulations of clusters composed of up to fifty molecules.

Gaining Insight into the Effect of Organic Interface Layer on Suppressing Ion Migration Induced Interfacial Degradation in Perovskite Solar Cells

AbstractIon migration induced interfacial degradation is a detrimental factor for the stability of perovskite solar cells (PSCs) and hence requires special attention to address this issue for the development of efficient PSCs with improved stability. Here, an “S‐shaped, hook‐like” organic small molecule, naphthalene diimide derivative (NDI‐BN), is employed as a cathode interface layer (CIL) to tailor the [6,6]‐phenylC61‐butyric acid methylester (PCBM)/Ag interface in inverted PSCs. By realizing enhanced electron extraction capability via the incorporation of NDI‐BN, a peak power conversion efficiency of 21.32% is achieved. Capacitance–voltage measurements and X‐ray photoelectron spectroscopy analysis confirmed an obvious role of this new organic CIL in successfully blocking ionic diffusion pathways toward the Ag cathode, thereby preventing interfacial degradation and improving device stability. The molecular packing motif of NDI‐BN further unveils its densely packed structure with π–π stacking force which has the ability to effectually hinder ion migration. Furthermore, theoretical calculations reveal that intercalation of decomposed perovskite species into the NDI clusters is considerably more difficult compared with the PCBM counterparts. This substantial contrast between NDI‐BN and PCBM molecules in terms of their structures and packing fashion determines the different tendencies of ion migration and unveils the superior potential of NDI‐BN in curtailing interfacial degradation.

Impact of PAH photodissociation on the formation of small hydrocarbons in the Orion Bar and the horsehead PDRs

ABSTRACT We study whether polycyclic aromatic hydrocarbons (PAHs) can be a weighty source of small hydrocarbons in photodissociation regions (PDRs). We modelled the evolution of 20 specific PAH molecules in terms of dehydrogenation and destruction of the carbon skeleton under the physical conditions of two well-studied PDRs, the Orion Bar, and the Horsehead nebula that represent prototypical examples of PDRs irradiated by ‘high’ and ‘low’ ultraviolet radiation field. PAHs are described as microcanonical systems. The acetylene molecule is considered as the main carbonaceous fragment of the PAH dissociation, as it follows from laboratory experiments and theory. We estimated the rates of acetylene production in gas phase chemical reactions and compared them with the rates of the acetylene production through the PAH dissociation. It is found that the latter rates can be higher than the former rates in the Orion Bar at AV < 1 and also at AV > 3.5. In the Horsehead nebula, the chemical reactions provide more acetylene than the PAH dissociation. The produced acetylene participate in the reactions of the formation of small hydrocarbons (C2H, C3H, C3H+, C3H2, C4H). Acetylene production via the PAH destruction may increase the abundances of small hydrocarbons produced in gas phase chemical reactions in the Orion Bar only at AV > 3.5. In the Horsehead nebula, the contribution of PAHs to the abundances of the small hydrocarbons is negligible. We conclude that the PAHs are not a major source of small hydrocarbons in both PDRs except some locations in the Orion Bar.

Optoplasmonic characterisation of reversible disulfide interactions at single thiol sites in the attomolar regime

Probing individual chemical reactions is key to mapping reaction pathways. Trace analysis of sub-kDa reactants and products is obfuscated by labels, however, as reaction kinetics are inevitably perturbed. The thiol-disulfide exchange reaction is of specific interest as it has many applications in nanotechnology and in nature. Redox cycling of single thiols and disulfides has been unresolvable due to a number of technological limitations, such as an inability to discriminate the leaving group. Here, we demonstrate detection of single-molecule thiol-disulfide exchange using a label-free optoplasmonic sensor. We quantify repeated reactions between sub-kDa thiolated species in real time and at concentrations down to 100’s of attomolar. A unique sensing modality is featured in our measurements, enabling the observation of single disulfide reaction kinetics and pathways on a plasmonic nanoparticle surface. Our technique paves the way towards characterising molecules in terms of their charge, oxidation state, and chirality via optoplasmonics.