Search

Direct separation of high purity ethylene (C2H4) from an ethane (C2H6)/ethylene mixture is a critical and challenging task owing to the very similar molecular size and physical properties of the two components. While some studies have attempted this separation, there is a lack of excellent porous materials with strong binding affinity for C2H6-selective adsorption via an energy-efficient adsorptive separation process. Herein, we report a titanium metal-organic framework with strong binding affinity and excellent stability for the highly efficient removal of C2H6 from C2H6/C2H4 mixtures. Single component adsorption isotherms demonstrated a larger amount of adsorbed ethane (1.16 mmol·g−1 under 1 kPa) and high C2H6/C2H4 selectivity (2.7) for equimolar C2H6/C2H4 mixtures, especially in the low-pressure range, which is further confirmed by the results of grand canonical Monte Carlo simulations for C2H6 adsorption in this framework. The experimental breakthrough curves showed that C2H4 with a high purity was collected directly from both 1:9 and 1:15 C2H6/C2H4 (volume ratio) mixtures at 298 K and 100 kPa. Moreover, the unchanged adsorption and separation performance after cycling experiments confirmed the promising applicability of this material in future.

The work presented in this article aims to develop reliable and predictive QSAR models to identify key molecular factors explaining the interaction effect (electronic / penetration), and establish reliable explanatory QSAR (quantitative relationship structure–activity) models for anticancer agents of the quinolin by using the theory of DFT. We studied the chemical structures of 29 9-chloro-11H-indeno [1,2-c] quinolin-11-one derivatives employing electronic and physicochemical descriptors. The present etude was introduce using: Principal Component Analysis (PCA), Multiple Linear Regression (MLR) and Multiple Nonlinear Regression (RNLM). The statistical quality of the RLM and RNLM models has proven to be effective in predicting cancer activity, but the RLM model is the best and most relevant because it has provided statistically significant results and has shown good internal stability and high predictability of new compounds. The squared correlation coefficients were 0.81 and 0.85 for MLR and MNLR models respectively. We deducted that the predicts obtained by the latest are more effective and widely better than the other models. Molecular docking studies revealed strong binding patterns of the synthesized quinolin with active site of cyclin-dependent kinase CK2. A good correlation is observed between anticancer activity and in molecular docking study.

Strained aromatic macrocycles based on cycloparaphenylenes (CPPs) are the shortest repeating units of armchair single-walled carbon nanotubes. Since the development of several new synthetic methodologies for accessing these structures, their properties have been extensively studied. Besides the fundamental interest in these novel molecular scaffolds, their application in the field of materials science is an ongoing topic of research. Most of the reported CPP-type macrocycles display strong binding toward fullerenes, due to the perfect match between the convex and concave π-surfaces of fullerenes and CPPs, respectively. Highly functionalized CPP derivatives capable of supramolecular binding with other molecules are rarely reported. The synthesis of highly functionalized [n]cyclo-2,7-pyrenylenes leads to CPP-type macrocycles with a defined cavity capable of binding non-fullerene guests with high association constants.

In this short Perspective, we discuss how recent dynamic live-cell imaging experiments have challenged our understanding of mechanisms driving functional molecular interactions in vivo. While we have generally considered the formation of functional biomolecular complexes as resulting from the stable assembly of two or more partner molecules, here we entertain the possibility that function may actually be maintained while molecules are rapidly exchanged within a complex. We postulate that at high effective concentrations, even very weak interactions can lead to strong binding site occupancy and thereby mediate function in a highly dynamic fashion. This new perspective in our definition of what represents a functional complex in living cells and in vivo could significantly alter how we define the nature of molecular transactions critical for mediating regulation in the cellular context. These less conventional principles also allow a broadening of the mechanistic options we should explore when interpreting essential biological processes such as gene regulation.

The C1-C3 receptors were synthesized by using coumarin and amines viz., 1-butylpiperazine (1), cis-myrtanylamine (2), and 3-methyldiphenyl amine (3) at room temperature without using harsh conditions. All the probes show beautiful and strong binding with Pb2+ ions among all the tested essential elements of human body. The binding is clearly seen and confirmed in UV-visible, NMR and HPLC studies. Also, all the substituted amines (1-3) are well known bioactives viz., piperazine as anthelmintic, cis-myrtanyl use for cannabinoid receptor (CB2) antagonists, 3-methyldiphenyl is used in probes for selective detection of explosive nitroaromatic compounds further increases their sensitivity for use as Pb2+ sensor. As they are already well in use for research on human body metabolomics their future introduction as sensors in the human body for lead toxicity is highly favourable.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal loss to human health and lives and has deeply impacted socio-economic growth. Remarkable efforts have been made by the scientific community in containing the virus by successful development of vaccines and diagnostic kits. Initiatives towards drug repurposing and discovery have also been undertaken. In this study, we compiled the known natural anti-viral compounds using text mining of the literature and examined them against four major structural proteins of SARS-CoV-2, namely, spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein. Following computational approaches, we identified fangchinoline and versicolactone C as the compounds to exhibit strong binding to the target proteins and causing structural deformation of three structural proteins (N, S and M). We recommend the inhibitory effects of these compounds from our study should be experimentally validated against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

As sugars form complexes with boronic acids, some sugars are used as additives for boron-containing pharmaceuticals. The binding constants of the rare sugar d-allulose with boronic acids were measu...

Structure-based nanocarrier design for protein delivery remains challenging and has rarely been documented in the literature. We herein present a facile computer-aided approach for rational and customized design of a unique linear–dendritic telodendrimer that self-assembles into a nanocarrier for therapeutic protein delivery, e.g., insulin. Virtual screening of a small-molecule library was performed to identify optimal protein binding moieties, which were conjugated precisely in the telodendrimer backbone preinstalled with charged moieties. We systematically tested our hypothesis and obtained significant correlations between the computational predictions and experimental results. The d-α-tocopherol (vitamin E)-containing nanocarrier showed strong binding affinity for insulin in both computational prediction and experiments, which led to improved blood glucose control. This study affirms the concept and validates the approach of structure-based nanocarrier design for protein delivery.

Salt-inducible kinases (SIKs) are calcium/calmodulin-dependent protein kinase (CAMK)-like (CAMKL) family members implicated in insulin signal transduction, metabolic regulation, inflammatory response, and other processes. Here, we focused on SIK2, which is a target of the Food and Drug Administration (FDA)-approved pan inhibitor N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (dasatinib), and constructed four representative SIK2 structures by homology modeling. We investigated the interactions between dasatinib and SIK2 via molecular docking, molecular dynamics simulation, and binding free energy calculation and found that dasatinib showed strong binding affinity for SIK2. Binding free energy calculations suggested that the modification of various dasatinib regions may provide useful information for drug design and to guide the discovery of novel dasatinib-based SIK2 inhibitors.

Selective separation of CO2/CH4 and C2H2/CH4 are promising for their high-purity industrial demand and scientific research on account of the similar molecular radius and physical properties. In this work, a unique 3D microporous MOF material [Cu(SiF6)(sdi)2]·solvents (1, sdi = 1,1′-sulfonyldiimidazole) was successfully constructed by cross-linking 1D coordination polymer chains. The dense functional active sites on the inner walls of the channel of 1a can provide strong binding affinities to CO2, C2H2, and thus effectively improve the gas separation performance of CO2/CH4 and C2H2/CH4.

Noncoding RNAs regulate gene expression in every domain of life. In bacteria, small RNAs (sRNAs) regulate gene expression in response to stress and are often assisted by RNA–chaperone proteins, such as Hfq. We have recently developed a bacterial three-hybrid (B3H) assay that detects the strong binding interactions of certain E. coli sRNAs with proteins Hfq and ProQ. Despite the promise of this system, the signal-to-noise has made it challenging to detect weaker interactions. In this work, we use Hfq–sRNA interactions as a model system to optimize the B3H assay, so that weaker RNA–protein interactions can be more reliably detected. We find that the concentration of the RNA–DNA adapter is an important parameter in determining the signal in the system and have modified the plasmid expressing this component to tune its concentration to optimal levels. In addition, we have systematically perturbed the binding affinity of Hfq–RNA interactions to define, for the first time, the relationship between B3H signal and in vitro binding energetics. The new pAdapter construct presented here substantially expands the range of detectable interactions in the B3H assay, broadening its utility. This improved assay will increase the likelihood of identifying novel protein–RNA interactions with the B3H system and will facilitate exploration of the binding mechanisms of these interactions.

Two colorimetric and ratiometric fluoride ion probes SHJ-1 and SHJ-2 based on the acylhydrazone skeleton have been developed. Among the eight anions (F−, Cl−, Br−, I−, ClO4−, H2PO4−, HSO4−, CH3COO−), the present probes showed high selectivity and sensitivity toward fluoride ion detection with obvious color change. Notably, the probe SHJ-1 exhibited a red shift of 145 nm upon fluoride sensing, which is the largest value among fluoride ion probes based on acylhydrazone derivates to date. 1HNMR titration study and theoretical calculations suggested that the strong binding of the probe SHJ-1 to fluoride as well as the further deprotonation may facilitate the intramolecular charge transfer transition. These two probes are 1 : 1 complexed with fluoride ions, and the detection limits were calculated to be 1.24 μM for SHJ-1 and 15.73 μM for SHJ-2.

Herein, we report a new bioprobe with aggregation-induced emission (AIE) characteristics by conjugation of a far-red/near-infrared emissive AIE luminogen and two polymyxinB peptides. Due to the strong binding effect between polymyxin B and the lipopolysaccharide in the cell wall of Gram-negative bacteria, the bioprobe can selectively visualize Gram-negative bacteria and effectively kill them via photodynamic treatment.

N‐heterocyclic carbenes (NHCs) have received significant attention as gold nanoparticle stabilizers due to their strong binding affinity towards gold. However, their tunability is limited by the difficulty in obtaining nonsymmetric NHCs. In this regard, N‐acyclic carbenes (NACs) are attractive alternatives due to their high synthetic versatility, allowing easy tuning of their steric and electronic properties towards specific applications. This work reports the first series of stable and monodisperse NAC‐functionalized gold nanoparticles. These particles with sizes ranging 3.8 to 11.6 nm were characterized using NMR, UV/Vis and TEM. The nanoparticles display good stability at elevated temperatures and for extended periods both dried or dispersed in a medium, as well as in the presence of exogenous thiols. Importantly, these NAC‐stabilized gold nanoparticles offer a promising and versatile alternative to NHC‐stabilized gold nanoparticles., Gold: N‐acyclic carbenes (NACs) have been shown to function as versatile ligand alternatives to N‐heterocyclic carbenes in the synthesis of a new series of stable plasmonic gold nanoparticles. The ease of preparing nonsymmetric NAC ligands and their synthetic tunability renders them especially attractive as gold nanoparticle stabilizers and opens up new possibilities in the design of gold nanoparticles for user‐specified functions (see figure).

Suitanes are a class of mechanically interlocked molecules (MIMs) that consist of two components: a body with limbs protruding outward and a suit that fits appropriately around it, so that there is no easy way for the suit to be removed from the body. Herein, we report the synthesis and characterization of a suit[3]ane, which contains a benzotrithiophene derivative (THBTT) with three protruding hexyl chains as the body and a 3-fold symmetric, extended pyridinium-based cage, namely, HexaCage6+, as the suit. Central to its realization is effective templation, provided by THBTT during cage formation, an observation that has been supported by the strong binding constant between benzotrithiophene (BTT) and the empty cage. The solid-state structure of the suit[3]ane reveals that the body is confined within the suit's cavity with its alkyl chains protruding outward through the orifices in the cage. Notably, such a seemingly unstable molecule, having three flexible alkyl chains as its only protruding limbs, does not dissociate after prolonged heating in CD3CN at 100 °C under pressure for 7 days. No evidence for guest exchange with the host was observed at this temperature in a 2:1 mixture of THBTT and HexaCage6+ in CD3CN. The results indicate that flexible protruding limbs are sufficient for a suit[3]ane to remain mechanically stable even at high temperatures in solution.

Cu/SSZ-13 has considered being a good candidate for NH3-SCR catalysts. However, in real world, Cu/SSZ-13 inevitably expose to alkali metals deposit and hydrothermal aging, and hence, the role of alkali ions (Na+ and K+) poisoning on the hydrothermal stability of Cu/SSZ-13 was investigated in this work. The Cu/SSZ-13 catalyst was treated with different loadings of alkali content at 600 °C or different hydrothermal temperatures at low alkali metal loading. Different from non-poisoned Cu/SSZ-13 catalysts under hydrothermal aging, the introduced alkali ions weaken the hydrothermal stability of Cu/SSZ-13 and make poisoned catalysts have inferior SCR performance. H2-TPR results demonstrate the presence of alkali ions lead to more copper ions transform to copper oxides species and the extents of transformation increase as the alkali contents and aging temperature increasing. Moreover, XRD results prove that the CHA framework collapse and, simultaneously, SiO2 and CuAlOx species form under high contents of alkali ions or high aging temperature. Besides, potassium invariably shows the severe deactivation because of a small hydrated diameter and strong binding ability. Our study reveals that diesel should pay attention to control the contents of alkali ions, especially for K+, in automotive products and the operating temperature in after-treatment applications.

espanolEsta investigacion se realizo para determinar el efecto de la temperatura sobre el contenido quimico y la estructura cristalina del clinker de cemento con un 10% de sustitucion de basalto sobre la masa de piedra caliza. El clinker de cemento esta hecho de la composicion de piedra caliza, piedra de basalto, arcilla, piedra de silice y arena de hierro. La piedra de basalto utilizada vino del area de East Lampung. La piedra de basalto ha cumplido el estandar ASTM C618 con un compuesto total de SiO2 + Al2O3 + Fe2O3 del 79,2%. La materia prima se mezclo, se molio, se formo en granulos con un tamano de 0,8 a 1,4 cm y se continuo con la combustion a temperaturas de calcinacion de 1000 ℃, 1100 ℃ y 1200 con un tiempo de retencion de 2 horas. Segun los resultados de la prueba XRF (fluorescencia de rayos X) de las tres muestras de clinker de cemento con variaciones de temperatura utilizadas, la muestra esta mas cerca del estandar a una temperatura de 1000 ℃. Para los resultados de la prueba de XRD (difraccion de rayos X), las tres muestras tienen estructuras cristalinas tetragonales, monoclinicas, romboedricas y ortorrombicas. En cuanto a los resultados de la prueba de MO, hubo una fuerte union entre arena de hierro, piedra caliza, arcilla y arena de silice caracterizada por una superficie lisa, mientras que las piedras de basalto que parecen agujeros negros no estaban completamente unidas. EnglishThis research was conducted to determine the effect of temperature on the chemical content and crystal structure of the cement clinker with 10% substitution of basalt on the mass of limestone. The cement clinker is made from the composition of limestone, basalt stone, clay, silica stone and iron sand. Basalt stone used came from the East Lampung area. The basalt stone has fulfilled ASTM C618 standard with a total compound of SiO2 + Al2O3 + Fe2O3 of 79.2%. The raw material was then mixed, milled, formed into pellets with a size of 0.8 - 1.4 cm and continued with combustion at calcination temperatures of 1000 ℃, 1100 ℃ and 1200 with a holding time of 2 hours. Based on the results of the XRF test (X-Ray Fluorecence) of the three cement clinker samples with variations in temperature used, the sample is closer to the standard at a temperature of 1000 ℃. For the XRD (X-Ray Diffraction) test results, the three samples have tetragonal, monoclinic, rhombohedral, and orthorhombic crystal structures. As for the MO test results, there was a strong binding between iron sand, limestone, clay, and silica sand characterized by a smooth surface while basalt stones that look like black holes were not completely bound.

Intrinsically disordered proteins (IDPs) are highly flexible molecules that undergo disorder to order transition through their interaction with other molecules. IDPs play a vital role in several biological processes ranging from molecular recognition to several human diseases through the protein-protein interaction. The dynamic flexibility of IDPs and their implications in several human diseases enable these molecules to serve as novel therapeutic targets. However, the challenging task is to develop novel drugs against IDPs because of their lack of stable structures and the nature of high conformational flexibility. In this study, we have calculated the dynamic binding effect of the supramolecular tweezer CLR01 against the intrinsically disordered HIV-1 Nef by employing molecular docking and dynamics simulation approaches. From docking results, we predicted the strong binding affinity of the tweezer with the target residues of Nef. The docking results were further validated from the molecular dynamics simulation studies confirming the conformational stability of Nef upon tweezer binding. These findings provide useful insights into the development of potent inhibitors for targeting Nef protein functions.

Nickel-catalyzed decarbonylation of acylsilanes is developed. In sharp contrast to cross-coupling reactions of acylsilanes, in which the silyl group serves as a leaving group, the silyl group is retained in the product in this decarbonylation reaction. Although the strong binding of the dissociated CO to the nickel center frequently hinders catalyst turnover in nickel-mediated decarbonylative reactions, this reaction can be catalyzed by nickel complexes bearing a CO ligand.

Photocatalytic conversion of nitrogen (N2) to ammonia (NH3) requires strong binding of N2 onto the catalyst surface and the generation of photoexcited electrons to activate the N≡N bond. In this st...

Although synthetic mimics of lectins can be extremely useful in biological and biomedical research, molecular recognition of carbohydrates has been hampered by their strong solvation in water and subtle structural differences among analogues. Molecularly imprinted nanoparticle receptors were prepared with glycans directly cleaved from glycoproteins. Functionalized with boroxole groups in the binding sites, these water-soluble synthetic lectins bound the parent glycoproteins selectively in water with an association constant of K(a) = 10(4)–10(5) M(−1). The strong binding enabled the receptors to protect the targeted glycans from enzymatic cleavage. When clicked onto magnetic nanoparticles, the receptors enabled facile isolation of glycoproteins from a mixture.

Catalysts with single-atom dispersions can not only minimize material usage but also exhibit fascinating activity. However, their superior catalytic properties can hardly be manipulated without a suitable substrate. Here, based on first principles calculations, we predicted that ferroelectric monolayer In2Se3 could be used as an appropriate substrate for Pt single-atom catalysts with strong binding energy and negative clustering energy. The Pt/In2Se3 catalyst showed extremely high activity for CO oxidation. Moreover, the catalytic performance can be well regulated by ferroelectric switch of monolayer In2Se3.

Tuberculosis (TB) is an airborne transmissible disease caused by Mycobacterium tuberculosis (Mtb), responsible for 1.3 million deaths per year. Due to increased cases of drug resistance to Mtb, a new treatment regime for TB needs to be discovered. ClpC1 plays a crucial role in the protein homeostasis of Mtb thus, presents as a promising target in controlling TB infection. The present study aimed to identify potential inhibitors for the ClpC1 N-terminal domain (ClpC1-NTD) by applying the relaxed complex scheme in virtual screening that accounts for the target and ligand flexibility. A filtered library of natural product compounds was virtually screened against each of the selected ClpC1-NTD dominant conformations from the ensemble generated using molecular dynamics simulation. The promising compounds with the strong binding affinity to ClpC1 protein were then further analysed for their molecular interactions. The stability of the most potent compound was examined through a complex MD simulation while the pharmacokinetics properties were gathered using SwissADME and pkCSM. The results showed that ligand NP132 formed a strong and stable complex with good pharmacokinetics and toxicological profile.

Synthesis and purification of metal clusters without strong binding agents by wet chemical methods are very attractive for their potential applications in many research areas. However, especially challenging is the separation of uncharged clusters with only a few number of atoms, which renders the usual techniques very difficult to apply. Herein, we report the first efficient separation of Ag2 and Ag3 clusters using the different entropic driving forces when such clusters interact with DNA, into which Ag3 selectively intercalates. After sequential dialysis of the samples and denaturalizing the DNA‐Ag3 complex, pure Ag2 can be found in the dialysate after extensive dialysis. Free Ag3 is recovered after DNA denaturation., Uncharged Ag2 and Ag3 clusters synthesized by a wet chemical procedure based on kinetics control, without using strong binding ligands, are separated by a simple procedure due to their very different chemical properties, namely, the different interaction with DNA. Using the specific intercalation ability of Ag3 with DNA, and the corresponding large entropy created in the surrounding water, we report a sequential dialysis/washing procedure allowing the complete separation of both type of clusters.

New chemical entities (NCEs) such as small molecules and antibody-drug conjugates have strong binding affinity for biological targets, which provide deep insights into structure-specific interactions for the design of future drugs. As structures of drugs increase in complexity, the importance of computational predictions comes into sharp focus. Knowledge of various computational tools enables us to predict the molecular properties, toxicity, and biological efficacy of the drugs and help the medicinal chemists to discover new drugs more efficiently. Newly approved drugs have higher affinities for proteins and nucleic acids and are applied for the treatment of human diseases. We have carried out the computational studies of 21 such NCEs, specifically small molecules and antibody-drug conjugates, and studied the biological efficacy of these drugs. Their bioactivity score and molecular and pharmacokinetic properties were evaluated using online computer software programs, viz., Molinspiration and Osiris Property Explorer. The SwissTargetPrediction tool was used for the efficient prediction of protein targets for the NCEs. The results indicated higher stability for the drug complexes due to a larger HOMO-LUMO gap. A high electrophilicity index reflects good electrophilic behavior and high reactivity of the drugs. Lipinski's ''rule of five'' indicated that most of the drug complexes are likely to be orally active. These drugs also showed non-mutagenic, non-tumorigenic, non-irritant, and non-effective reproductive behavior. We hope that these studies will provide an insight into molecular recognition and definitely help the medicinal chemists to design new drugs in future.

Food safety monitoring assays based on synthetic recognition structures such as aptamers are receiving considerable attention due to their remarkable advantages in terms of their ability to bind to a wide range of target analytes, strong binding affinity, facile manufacturing, and cost-effectiveness. Although aptasensors for food monitoring are still in the development stage, the use of an electrochemical detection route, combined with the wide range of materials available as transducers and the proper immobilization strategy of the aptamer at the transducer surface, can lead to powerful analytical tools. In such a context, employing aryldiazonium salts for the surface derivatization of transducer electrodes serves as a simple, versatile and robust strategy to fine-tune the interface properties and to facilitate the convenient anchoring and stability of the aptamer. By summarizing the most important results disclosed in the last years, this article provides a comprehensive review that emphasizes the contribution of aryldiazonium chemistry in developing electrochemical aptasensors for food safety monitoring.

To investigate the active ingredients and mechanism of Poria cocos (Schw.) wolf (PCW) against stroke based on network pharmacology. TCMSP database was used to obtain active ingredients of PCW, and targets of ingredients were retrieved from the SwissTargetPrediction database. The targets of stroke were searched from Genecards and PALM-IST database, Venny 2.1 was used to screen the common targets between drugs and disease, and the protein-protein interaction network of the targets was constructed by String 11.0. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of targets were based on Metascape database. The molecular docking verification was carried out by SwissDock. 6 chemical active components were screened from PCW, and acts on 35 stroke targets. Go enrichment analysis showed that the biological process mainly involved in blood circulation, etc. KEGG pathway enrichment analysis showed that PCW played a therapeutic role in stroke by regulating neuroactive ligand-receptor interaction, etc. The molecular docking results showed that the trametenolic acid and 3beta-Hydroxy-24-methylene-8-lanostene-21-oic acid had the strong binding effect with TNF, etc. PCW against stroke may be related to its multiple targets and multiple signaling pathways, provide theoretical basis for further experimental and clinical research.

The nine-amino-acid activation domain (9aaTAD) is defined by a short amino acid pattern including two hydrophobic regions (positions p3-4 and p6-7). The KIX domain of mediator transcription CBP interacts with the 9aaTAD domains of transcription factors MLL, E2A, NF-kB, and p53. In this study, we analyzed the 9aaTADs-KIX interactions by nuclear magnetic resonance. The positions of three KIX helixes α1-α2-α3 are influenced by sterically-associated hydrophobic I611, L628, and I660 residues that are exposed to solvent. The positions of two rigid KIX helixes α1 and α2 generate conditions for structural folding in the flexible KIX-L12-G2 regions localized between them. The three KIX I611, L628, and I660 residues interact with two 9aaTAD hydrophobic residues in positions p3 and p4 and together build a hydrophobic core of five residues (5R). Numerous residues in 9aaTAD position p3 and p4 could provide this interaction. Following binding of the 9aaTAD to KIX, the hydrophobic I611, L628, and I660 residues are no longer exposed to solvent and their position changes inside the hydrophobic core together with position of KIX α1-α2-α3 helixes. The new positions of the KIX helixes α1 and α2 allow the KIX-L12-G2 enhanced formation. The second hydrophobic region of the 9aaTAD (positions p6 and p7) provides strong binding with the KIX-L12-G2 region. Similarly, multiple residues in 9aaTAD position p6 and p7 could provide this interaction. In conclusion, both 9aaTAD regions p3, p4 and p6, p7 provide co-operative and highly universal binding to mediator KIX. The hydrophobic core 5R formation allows new positions of the rigid KIX α-helixes and enables the enhanced formation of the KIX-L12-G2 region. This contributes to free energy and is the key for the KIX-9aaTAD binding. Therefore, the 9aaTAD-KIX interactions do not operate under the rigid key-and-lock mechanism what explains the 9aaTAD natural variability.

Unfractionated heparin (UFH), a naturally occurring anionic polysaccharide, is widely used as an anticoagulant agent in clinical practice. When overdosed or used in sensitive patients, UFH may cause various risks and a UFH neutralizer needs to be administered immediately to reverse heparinization. However, the most common UFH neutralizer, protamine sulfate, often causes various adverse effects, some of which are life-threatening. Herein, we designed a highly biocompatible, oligoethylene glycol functionalized guanidinocalixarene (GC4AOEG) as an antidote against UFH. GC4AOEG and UFH exhibited a strong binding affinity, ensuring specific recognition and neutralization of UFH by GC4AOEG in vitro and in vivo. As a consequence, UFH-induced excessive bleeding was significantly alleviated by GC4AOEG in different mouse bleeding models. Additionally, no adverse effects were observed during these treatments in vivo. Taken together, GC4AOEG, as a strategically designed, biocompatible artificial receptor with strong recognition affinity towards UFH, may have significant clinical potential as an alternative UFH reversal agent., An oligoethylene glycol functionalized guanidinocalix[4]arene was developed as a safe antidote against heparin, via specific recognition and neutralization of heparin in vitro and in vivo.

The strong binding between CsPbBr3 nanocrystals and methyl viologen induces a long-lived charge-separated state following band gap excitation with important implications in photocatalytic processes...

Currently the development of technologies for labeling somatostatin with technetium-99m for diagnosing radionuclide neuroendocrine tumors is under way. Somatostatin analogues are binded with technetium99m only by the preliminary addition of a chelating agent. Therefore, it is important to develop a method for preparation of an octreotide derivative by modifying octreotide with precursors: ligands with high chelating ability for its tight binding with technetium-99m. ω-Bis(pyridin-2-ylmethyl)amino)aliphatic acids can be used successfully as such precursors.The purpose of the study was to develop a method for obtaining a new octreotide derivative for diagnosing neuroendocrine tumors.Materials and methods. The somatostatin octreotide analogue was used as the object of the study; succinimid-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used as a chelating agent. Methods of high performance liquid chromatography and mass spectrometry were used to separate and analyze the synthesized compounds.Results. A method to produce an original octreotide derivative using a succinimid-1-yl 6-(bis(pyridin2-ylmethyl)amino)hexanoate as a chelating agent was proposed. The conditions of analytical and semipreparative HPLC for the analysis and purification of the active octreotide derivative (a monosubstituted derivative of the amino acid residue of D-phenylalanine) were suggested.Conclusion. The synthesized derivative of octreotide has a chelating center for strong binding to technetium-99m in its structure, which can be useful for diagnosing neuroendocrine tumors.

Ebola virus (EBOV), a member of the filovirus family, is an enveloped negative-sense RNA virus that causes lethal infections in humans and primates. Thousands of people have died from the Ebola virus disease (EVD) in West Africa, and no specific antiviral medication and treatment have been approved for EVD. Although the development of an EBOV vaccine is promising, immunity to any vaccine is not immediate. Here, we computationally analysed the structure of EBOV glycoprotein GP2 (GP2EBOV) and designed RNA aptamers that recognize and inhibit it. The aptamers specifically bind to conserved arginine residues (Arg587 and Arg596) located in the C-terminal coiled-coil region of GP2EBOV. Molecular docking of the synthetic RNA aptamers with the ectodomain of GP2EBOV revealed that the optimized orthogonal RNA aptamers have strong binding affinities with the coiled-coil region of GP2EBOV. The characterized RNA aptamers may facilitate strategies to block replication of EBOV and related Filoviruses, and thus may serve as important antivirals to reduce mortality associated with these infections.

We present a detailed investigation of the effect of the crystallographic structure of the HIV-1 protease (PR) on the binding energy of different classes of inhibitors obtained from docking simulations. The crystal structures of 222 HIV-1 proteases (in wild-type and mutant forms) and 202 inhibitors were downloaded from appropriate databases. A cross-docking approach (docking of all 202 inhibitors to all 222 PR structures) using Autodock Vina was implemented. The protease structures were clustered using a Kohonen self-organization map analysis of the data matrix of docking energies. The obtained clusters of PRs were correlated with the x-y-z coordinates of the PR structures to identify structural segments underlying this clustering. The PR structures were clustered into 4 classes. One of these classes exhibits rather strong binding with almost all inhibitors, while another class exhibits rather weak binding. The remaining two classes are intermediate in binding strength. The selectivity ratio indices for the carbon-alpha atoms of the PR structures indicate that conformational motion of residues outside the binding pocket contributes significantly to the discrimination of the 4 classes.

To design a new therapeutic agent for Spleen Tyrosine Kinase (Syk), analysis of ligand-based pharmacophore modeling, 3D QSAR and molecular docking studies were performed. A consortium of 99 molecules with different molecular scaffolds (9.36 > pIC50>5.49) were gathered. Generated models were anatomized and essential properties required for the inhibition of Syk were assimilated. Comparative analyses of highly active, moderately active and inactive molecules helped in explaining the interactions necessary for ligand receptor binding. Further, model validation by collating the crystal structures of Syk also proved its applicability. Based on the analysis, imidazopyrazine based ligands show a strong binding affinity towards Syk active site along with good ADME properties. Going forward this study may pave a new way for designing and synthesising Syk inhibitors with better biological activities.

Inverted perovskite solar cells (PSCs) have stood out from the promising candidates for portable power source applications. Their advantageous features such as high efficiency, low cost, light weight and flexibility can be retained when a robust and compact hole transport layer (HTL) is fabricated using a low-temperature technology. To maximize the mechanical feature, the integration of graphene-derived nanomaterials is a method of choice owing to their superior physical and mechanical properties. Herein, we report an innovative method of fabricating efficient PSCs by means of inserting conjugated polyelectrolyte PTFTS interlayers between the perovskite and graphene oxide (GO) HTL. Results show that the amphiphilic polymer interlayer facilitates the growth of perovskite grains, passivates interfacial trap-states, forms better energetic alignment, and increases intermolecular interaction between PTFTS and perovskite. More importantly, strong binding force between GO and PTFTS enables uniform interlayer films obtained from a simple dip-coating method. The facile processability of the PTFTS-modified GO has been successfully extended to scalable fabrication of flexible device (1.08 cm2) with excellent device efficiency over 17.0%, the highest reported value so far for large-area flexible PSCs. This front-contact interfacial engineering offers an efficient strategy towards the widespread application of solution-processable graphene materials in practical perovskite devices.

Controllable protein adsorption on solids is of great importance in many modern technological applications. The role of the water phase in mediating the protein-surface interactions, however, still remains poorly understood. Herein, we employ free energy calculations to systematically explore the mechanisms of the surface adsorption/bioresistance correlating with the interfacial water layers. The studied peptide shows strong binding affinity with the hydrophobic surface, as illustrated by a monotonic decrease in the free energy profile with no energy barriers. However, the surface bioresistance could be triggered in two distinct ways, by not only an enhancement of the surface-water interactions, but also increased interactions between the water and adsorbates. The enhanced surface-water interactions decrease the tendency of the surface dehydration and the subsequent adsorbate penetration into the surface-bound water layers, thus leading to the surface bioresistance. On the other hand, the enhanced water-adsorbate interactions could promote water stabilization of the adsorbate in the bulk solution, effectively preventing the peptide adsorption. Our results further elucidate that the increase in the peptide size favors its adsorption on the hydrophobic surface, but go against the adsorption on the hydrophilic surface. The mechanisms revealed here may facilitate the design of novel proteins/peptides, materials, and solvents for a controllable adsorption at a solid-water interface.

The present study aims to investigate the effect of Longan Arillus extract (ELA) on oral absorption of bioactive peptides (cationic P1: VEGNLQVLRPR, anionic P2: HNLDTQTESDV) derived from defatted walnut meal hydrolysates (DWMH). Oral co-delivery of ELA with DWMH led to a significantly higher maximum blood concentration of P2 in rats than delivering DWMH alone. Endocytosis pathway of P2 in intestinal epithelia cells was altered by ELA, probably resulting from formation of uniform microparticles by mixing of P2 and ELA. Results of isothermal calorimetry proved strong binding between molecules of P2 and ELA at a molar ratio of 1:1. On the contrary, the absorption of cationic P1 remained unchanged after co-delivery of ELA, probably resulting from the complicated patterns of binding between ELA and P1 molecules. In conclusion, we found the enhancing effect of polysaccharides on absorption of peptides by formation of microparticles, which could be predicted by molecule binding.

Dinickel complexes promote stoichiometric Pauson–Khand reactions of enynes and CO (g). However, catalytic turnover is precluded by the strong binding of CO to the Ni2 active site. This article describes the use of M(CO)x reagents as stoichiometric CO precursors in Ni2-catalyzed carbonylation reactions. As part of these studies, well-defined heterotrinuclear Ni2Fe, Ni2Co, and Ni2Mn carbonyl clusters are synthesized using the [NDI]Ni2 platform as a template (NDI = naphthyridine–diimine).

The present research paper reports a convenient synthesis of novel 4-(benzylideneamino)-5-pentadecyl-2H-1,2,4-triazol-3(4H)-ones and their in vitro antioxidant assay. The synthesized azomethine-triazole hybrids are characterized using FT-IR, multi nuclear NMR and elemental analysis (CHN). Oxidative potential of the synthesized derivatives is assessed by performing various in vitro antioxidant and α-amylase assays. The best antioxidant potential was displayed by 4d followed by 4a, 4e and 4i. Molecular docking simulations revealed that the tested azomethine-triazole 4a showed strong binding inside the active-site gorges of the α-amylase. A striking agreement was obtained as the best-docked poses showed important binding features mostly based on interactions due to triazolone moiety of the azomethine linkage. The docking computations coupled with the experimental findings ascertained that the compound 4a can serve as a potential scaffold for the development of a novel class of α-amylase inhibitors.

Patients with Human epidermal growth factor receptor type 2 (Her2) overexpression are associated with aggressive tumor growth and poor clinical outcomes. Bispecific antibodies targeting Her2 have recently exhibited potent effects on Her2 signal inhibition. In this study, a novel biparatopic anti-Her2 bispecific antibody (Bp-Bs) was constructed by linking a single anti-CD3 Fab with two different anti-Her2 single-domain antibodies targeting non-overlapping epitopes of Her2. The Bp-Bs demonstrated strong binding on Her2-positive cells and potent cytotoxicity on Her2-positive tumor cells, even Her2-low expression cells, suggesting that biparatopic bispecific antibodies may have improved therapeutic benefits on broad Her2 patient populations. Keywords: Her2, bispecific, biparatopic, bivalent, single domain, antibody, trastuzumab

This review was organized to describe the progress made in the integration of nanostructural materials into electrochemical analytical tools for the quantification of endocrine disrupting chemicals (EDCs) in diverse sample matrices (e.g., environmental and biological samples). Here, we focused mainly on seven major EDCs: alkylphenols/phenols, bisphenol A, parabens, triclosan, phthalates, pesticides, and natural/synthetic sex hormones. All of them are known to exhibit endocrine disruption by strong binding with estrogen receptors to pose serious health risks (e.g., cancerous tumors and disorders in various organs). To realize rapid, selective, and sensitive detection of EDCs, the use of nanostructured materials has become a fascinating option due to many merits (e.g., automation, fast response, good accuracy, and high selectivity/sensitivity). Here, the performance of sensing tools built using nanomaterials was assessed for the detection of EDCs in various sample matrices. Our discussion was extended further to cover the future prospects on this fascinating research field.

Ligand-targeting specific liposomal probes are increasingly used as imaging and delivery vehicles for in vivo diagnosis. Thereinto, the ligand variety and density profoundly affect the binding behaviors toward the target. The synergetic effect of different ligands could be achieved only when the optimized molecular-recognition configuration occurred. In this study, we construct a dual-peptides-targeting liposomal probe named BTLS that could synergistically bind two different sites of prominin-1, a cancer stem cell marker. At the distance of 11 Å between the two new peptides, ligands could insert into the hollow pocket of prominin-1 and BTLS could achieve the appropriate spatial structure, showing the strong binding affinity in both cellular and in vivo levels. It is indicated that the design of density-optimized peptide-targeted liposomes could be promising to maximize the multifunctional targeting effects on the cancer theranostics.

Many organic co-solutes are known to stabilize or to destabilize native structures of proteins or DNA. Most of these effects can be explained by co-solute binding or exclusion mechanisms. A beneficial approach to study the underlying principles relies on the computation of Kirkwood–Buff integrals, which can be also used to derive detailed expressions for transfer free energies and changes of the chemical equilibrium between the unfolded and the native states. In this article, we use the framework of Kirkwood–Buff theory in order to study the influence of ectoine on the stability of short DNA hairpins. Our results highlight a strong binding of ectoine, which reveals a pronounced destabilization of DNA in good agreement with experimental findings.

A porphyrinic metal-organic framework, PCN-222, was employed for the fast and sensitive determination of cysteine (Cys) based on its fluorescence (FL) property. A “turn-on” sensor was easily established based on the instant metalation of PCN-222 with Hg2+, and the sensing for Cys primarily derived from the strong binding between Hg and Cys, with the PCN-222 FL fast recovered via the rapid and efficient release of Hg. A more than two orders of magnitude in the linear dynamic range and a limit of detection as low as 60 nM were obtained by using the proposed method based on FL measurement. In particular, the sensing could also be accomplished in a visual manner, with the color change of Hg-metalated PCN-222 easily observed by naked eyes upon the addition of Cys as low as 100 nM. The proposed strategy for Cys sensing also showed advantages including facile preparation and cyclic usage of the probe, fast response (1 min) to Cys, high sensitivity for both FL and visual sensing, and no extra additives such as catalysts nor chromogenic substrates.

Owing to the rapid increase of Hg(II) ions in water resources, the design and development of new adsorbents for Hg(II) removal are becoming a significant challenge in environmental protection. Herein, a thiol-functionalized metal-organic framework (SH-MiL-68(In)) was successfully prepared through a post-synthesis modification procedure, and the framework intactness and porosity were well maintained after this process. SH-MiL-68(In) exhibited selective adsorption performance for Hg(II) ions in water. Meanwhile, SH-MiL-68(In) also shows a high adsorption capacity (450 mg g-1), large adsorption rate (rate constant k2 = 1.25 g mg-1 min-1), and good recycling of adsorption capacity toward Hg(II) ions. The excellent adsorption performance resulted from the strong binding interactions between -SH soft basic groups and Hg(II) soft acidic ions.

Marine mussels harness catechol-rich foot proteins with hierarchically assembled nanostructures to achieve robust adhesion in the dynamic underwater environment. Herein, mimicking the chemical composition and hierarchical nanostructure of mussel foot proteins, a silk-based sealant (named SFT) with superior wet adhesion and instant hemostasis was developed by introducing tannic acid (TA) into silk fibroin (SF). The presence of TA containing abundant phenolic moieties triggered the conformational transition of SF from random coil to β-sheet and the hierarchical assembly of nanofibrillar structures, imparting SFT with high intrinsic toughness (123.1 kJ m−3). The phenolic moiety, with strong binding affinity to nucleophiles in tissue biomolecules, also endowed SFT with tough adhesion to wet tissues (strength ≈134.1 kPa) even in the presence of blood and robust tissue motions (e.g., bleeding heart) and exhibited instant hemostatic capability (within 30 s). Given the unprecedented combination of tough adhesion and instant homeostasis, the engineered SFT can fulfil unmet challenges and serve as a promising surgical sealant for suturelessly sealing ruptured tissues in wet and dynamic biological environments.