Minimal Structural Modifications Research Articles

Tetraethylenepentamine-modified Cu2(OH)PO4 for efficient CO2 capture

This study focused on creating tetraethylenepentamine (TEPA) modified copper hydroxyl phosphate (Cu2(OH)PO4) adsorbents via physical impregnation. The TEPA-modified Cu2(OH)PO4 adsorbents were analyzed for structure and characteristics through SEM, XPS, TGA, N2 adsorption–desorption studies. The effects of different parameters (TEPA contents, temperatures, flow rates and CO2 concentrations) and cyclic stability were evaluated. Kinetics, thermodynamics and density functional theory (DFT) calculations were employed to understand the impact of TEPA modification on Cu2(OH)PO4 for CO2 adsorption. Experimental results showed that a 50 wt% loading yielded optimal results, with a maximum surface area of 65.12 m2/g, a pore volume of 0.29 cm3/g, and a maximum adsorption capacity of 6.54 mmol/g. The amine efficiency is extraordinary which reached 67 %. The best performance occurred at 60 °C, 30 ml/min gas flow, and 15 vol% CO2 concentration. The pseudo-second-order kinetic model better described the CO2 adsorption process. The adsorption process was found to be exothermic at 20–60 °C and endothermic at 60–80 °C, suggesting physical–chemical co-adsorption and chemical adsorption, respectively. The adsorption activation energy is 34.322 kJ/mol. The DFT shows the adsorption energy ranged from −0.565 eV to −5.584 eV, indicating coexistence of physical and chemical adsorption. The d-band theoretical calculation shows that TEPA doping is beneficial to the adsorption of CO2 by Cu2(OH)PO4. Minimal structural modification of the adsorbate was observed, with bond lengths changing by less than 1 %. The density of states (DOS) curve shifted toward lower-energy states after adsorption, suggesting a more stable structural configuration post-adsorption. We have proved that TEPA-Cu2(OH)PO4 has good adsorption for CO2 and is an efficient green adsorption material.

Fluorine and chlorine substituted adamantyl-urea as molecular tools for inhibition of human soluble epoxide hydrolase with picomolar efficacy

Series of 1,3-disubstituted ureas and diadamantyl disubstituted diureas with fluorinated and chlorinated adamantane residues were shown to inhibit human soluble epoxide hydrolase (sEH) with inhibition potency ranging from 40 pM to 9.2 nM. The measured IC50 values for some molecules were below the accuracy limit of the existing in vitro assays. Such an increase in activity was achieved by minimal structural modifications to the molecules of known inhibitors, including 4-[trans-4-(1-adamantylcarbamoylamino)cyclohexyl]oxybenzoic acid. For the chlorinated homologue of the latter the sharp jump in inhibitory activity can be (according to molecular dynamics data) the result of interactions – Cl-π interaction. Considering the extremely high inhibitory activity, acceptable solubility and partial blockage of metabolically sensitive centres in their structures, some compounds are of interest for further in vivo biotesting.

Flavin based supramolecular gel displaying multi-stimuli triggered sol-gel transition.

Herein, we report the design and synthesis of an amphiphilic flavin analogue as a robust low molecular weight gelator involving minimal structural modification. Four flavin analogues were evaluated for their gelation capabilities and the flavin analogue with antipodal positioning of the carboxyl and octyl functionalities was found to be the most efficient gelator with the minimum gelation concentration being as low as 0.03 M. A wide range of solvents were used for gelation studies suggesting its widespread applicability. Morphological, photophysical and rheological characterization studies were performed to fully characterize the nature of the gel. Interestingly, reversible multiple stimuli responsive sol-gel transition was observed with changing pH and redox activity, while metal screening showed specific transition in the presence of ferric ions. The gel was able to differentiate between ferric and ferrous species with well-defined sol-gel transition. The current results potentially offer a redox-active flavin-based material as a low molecular weight gelator for the development of next-generation materials.

Acidic Shift of Optimum pH of Bovine Serum Amine Oxidase upon Immobilization onto Nanostructured Ferric Tannates

Protein–nanoparticle hybrids represent entities characterized by emerging biological properties that can significantly differ from those of the parent components. Herein, bovine serum amine oxidase (i.e., BSAO) was immobilized onto a magnetic nanomaterial constituted of surface active maghemite nanoparticles (i.e., SAMNs, the core), surface-modified with tannic acid (i.e., TA, the shell), to produce a biologically active ternary hybrid (i.e., SAMN@TA@BSAO). In comparison with the native enzyme, the secondary structure of the immobilized BSAO responded to pH variations sensitively, resulting in a shift of its optimum activity from pH 7.2 to 5.0. Conversely, the native enzyme structure was not influenced by pH and its activity was affected at pH 5.0, i.e., in correspondence with the best performances of SAMN@TA@BSAO. Thus, an extensive NMR study was dedicated to the structure–function relationship of native BSAO, confirming that its low activity below pH 6.0 was ascribable to minimal structural modifications not detected by circular dichroism. The generation of cytotoxic products, such as aldehydes and H2O2, by the catalytic activity of SAMN@TA@BSAO on polyamine oxidation is envisaged as smart nanotherapy for tumor cells. The present study supports protein–nanoparticle conjugation as a key for the modulation of biological functions.

Inhibition of β-Amyloid Aggregation in Alzheimer's Disease: The Key Role of (Pro)electrophilic Warheads.

Catechols have been largely investigated as antiaggregating agents toward β-amyloid peptide. Herein, as a follow up of a previous series of hydroxycinnamic derivatives, we synthesized a small set of dihydroxy isomers for exploring the role of the reciprocal position of the two hydroxyl functions at a molecular level. Para- and ortho-derivatives effectively reduced amyloid fibrillization, while the meta-analogue was devoid of any activity in this respect. Electrochemical analyses showed that the antiaggregating potency correlates with the oxidation potential, hence indicating the proelectrophilic character as a prerequisite for activity. Interestingly, mass spectrometry studies and quantum mechanical calculations revealed different modes of action for active para- and ortho-derivatives, involving covalent or noncovalent interactions with β-amyloid. The distinctive mode of action is also translated into a different cytotoxicity profile. This work clearly shows how apparently minimal structural modifications can completely change the compound behavior and generate alternative mechanisms of action of proelectrophilic chemical probes.

Structural Modification of Polymers Functionalized with Mango Leaf Extract by Supercritical Impregnation: Approaching of Further Food and Biomedical Applications.

Identifying new polymers from natural resources that can be effectively functionalized can have a substantial impact on biomedical devices and food preservation fields. Some of these polymers would be made of biodegradable, renewable and compostable materials, and present the kind of porosity required to effectively carry active compounds that confer on them the desired properties for their intended applications. Some natural extracts, such as mango leaf extract, have been proven to have high levels of antioxidant, antimicrobial or anti-inflammatory properties, making them good candidates for controlled-release applications. This work intends to investigate the supercritical impregnation of different types of polymers (ABS, PETG, TPU, PC and PCL) with mango leaf extract. The influence of temperature and pressure on the polymers’ structure (swelling and foaming processes) and their different behaviors have been analyzed. Thus, TPU and PC experience minimal structural modifications, while PETG, PCL and ABS, on the other hand, suffer quite significant structural changes. TPU and PETG were selected as the representative polymers for each one of these behaviors to delve into mango leaf extract impregnation processes. The bioactive capacity of the extract is present in either impregnated polymer, with 25.7% antioxidant activity by TPU processed at 35 °C and 100 bar and 32.9% antioxidant activity by PETG impregnated at 75 °C and 400 bar.

Systematic Exploration of Furoindolizine-Based Molecular Frameworks towards a Versatile Fluorescent Platform.

The photophysical behaviors of fluorescent molecules largely determine their major utility in biological studies. Despite their well-defined characteristics, classical fluorophores have often been challenged by their limited synthetic methodology and tunability in adjusting intrinsic optical properties. A novel heterocyclic core equipped with modular functional groups could offer the flexibility to control its photophysical properties with a minimum synthetic effort. By conducting a systematic analysis guided by quantum calculations, we proposed the furoindolizine-based molecular framework as a unique fluorescent platform capable of providing versatile photophysical properties with minimal structural modification. A broad tunability of furoindolizine derivatives' photophysical properties such as emission wavelength, Stokes shift, fluorescent brightness, and charge transfer characteristics was achieved through synergistic interaction between two functional moieties. Furthermore, this modular platform led to live-cell imaging probes with two distinct optical features simply by reorganizing a pair of functional moieties.

Area-Type Electronic Bipolar Switching Al/TiO1.7/TiO2/Al Memory with Linear Potentiation and Depression Characteristics.

In electronic bipolar resistive switching (eBRS), the electron trapping and detrapping at the defect sites within the switching layer, such as the highly defective TiO1.7 in this study, constitute the switching mechanism. It is an appealing candidate solution to the nonuniformity issue of resistive switching memory. However, TiO1.7-based eBRS has suffered from a lack of endurance and retention. In this study, a 7 nm-thick stoichiometric TiO2 layer is interposed between an Al bottom electrode and a 50 nm-thick TiO1.7 layer, which is in contact with an Al top electrode. Despite the minimal structural modification, improvements in the electrical performance were substantial. The off-to-on state resistance ratio of 20 and the resistance values could be retained up to 30 000 direct current sweep cycles and 106 alternating current pulse switching cycles. Data retention also significantly improves. Moreover, the device is electroforming-free and shows fully area-type switching characteristics. Such notable improvements are attributed to the favorable energy band structure of the Al/TiO1.7/TiO2/Al structure. The device shows almost linear potentiation and depression characteristics after the repeated pulse voltage applications, which significantly improves the accuracy of the neural network, the synapses of which are composed of the Al/TiO1.7/TiO2/Al memory cells.

Validation of a Bioanalytical Method for the Determination of Synthetic and Natural Cannabinoids (New Psychoactive Substances) in Oral Fluid Samples by Means of HPLC-MS/MS.

New psychoactive substances (NPS) represent an important focus nowadays and are continually produced with minimal structural modifications in order to circumvent the law and increase the difficulty of identifying them. Moreover, since there are a high number of different compounds, it is arduous to develop analytical screening and/or confirmation methods that allow the identification and quantification of these compounds. The aim of this work is to develop and validate a bioanalytical method for detecting new synthetic drugs in biological samples, specifically oral fluid, using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) with minimal sample pretreatment. Oral fluid samples were simply centrifuged and denaturized with different rapid procedures before injection into the LC-MS/MS system. Calibration curves covered a linear concentration range from LOQ to 100 ng/mL. Validation parameters such as linearity, precision, accuracy, selectivity, matrix effect and thermal stability were evaluated and showed satisfactory results, in accordance with US Food & Drug Administration guidelines. The inter-day analytical bias and imprecision at two levels of quality control (QC) were within ±15% for most compounds. This method was able to identify and calculate the concentration of 10 NPS validated in this biological sample, even in the presence of matrix effect.

Aromatic Stacking Facilitated Self-Assembly of Ultrashort Ionic Complementary Peptide Sequence: β-Sheet Nanofibers with Remarkable Gelation and Interfacial Properties.

Understanding peptide self-assembly mechanisms and stability of the formed assemblies is crucial for the development of functional nanomaterials. Herein, we have adopted a rational design approach to demonstrate how a minimal structural modification to a nonassembling ultrashort ionic self-complementary tetrapeptide FEFK (Phe4) remarkably enhanced the stability of self-assembly into β-sheet nanofibers and induced hydrogelation. This was achieved by replacing flexible phenylalanine residue (F) by the rigid phenylglycine (Phg), resulting in a constrained analogue PhgEPhgK (Phg4), which positioned aromatic rings in an orientation favorable for aromatic stacking. Phg4 self-assembly into stable β-sheet ladders was facilitated by π-staking of aromatic side chains alongside hydrogen bonding between backbone amides along the nanofiber axis. The contribution of these noncovalent interactions in stabilizing self-assembly was predicted by in silico modeling using molecular dynamics simulations and semiempirical quantum mechanics calculations. In aqueous medium, Phg4 β-sheet nanofibers entangled at a critical gelation concentration ≥20 mg/mL forming a network of nanofibrous hydrogels. Phg4 also demonstrated a unique surface activity in the presence of immiscible oils and was superior to commercial emulsifiers in stabilizing oil-in-water (O/W) emulsions. This was attributed to interfacial adsorption of amphiphilic nanofibrils forming nanofibrilized microspheres. To our knowledge, Phg4 is the shortest ionic self-complementary peptide rationally designed to self-assemble into stable β-sheet nanofibers capable of gelation and emulsification. Our results suggest that ultrashort ionic-complementary constrained peptides or UICPs have significant potential for the development of cost-effective, sustainable, and multifunctional soft bionanomaterials.

ChemInform Abstract: A Review of Whole Cell Wall NMR by the Direct‐Dissolution of Biomass

AbstractReview: 89 refs.

Approaches to polyunsaturated sphingolipids: new conformationally restrained analogs with minimal structural modifications

Conformationally restrained sphingolipids 1–4, arising from the introduction of a polyene or a polyenyne moiety as part of the sphingoid backbone, have been synthesized. While addition of polyene acetylides 6 and 7 to Garner's aldehyde afforded the corresponding Felkin-Anh anti-addition adducts, addition of alkenylzirconocenes showed no diastereoselectivity. This behaviour was also observed from protected serinal 14, which allowed the synthesis of the acid-sensitive pentaene sphingosine backbone present in ceramide 4. Despite the inherent limitations of the synthetic approaches here reported, their application to such highly conjugated polyene sphingoid analogs is unprecedented.

Transmission expansion planning model considering conductor thermal dynamics and high temperature low sag conductors

The means for transporting more power through an existing transmission corridor have been given considerable attention in recent studies. Reconductoring a path with a conductor that has a higher thermal capacity, such as a high temperature low sag (HTLS) conductor, is one possible option with minimal structural modification and out-of-service time. Parallel line additions or HTLS parallel line additions are other options that can increase transfer capabilities and reduce operating costs. Thermal constraint relaxation is another option, which is an operational based method that allows the line flow to exceed the steady-state line rating for a certain penalty price. Since such operation may deteriorate the expected service time of the conductor, the penalty price should be determined properly. In this study, the above options are captured to create the proposed transmission expansion planning model. In addition, a conductor degradation model is introduced to capture the associated degradation costs due to operating conductors at elevated temperatures. Numerical simulations conducted on the IEEE-24 and IEEE-118 bus system indicate the effectiveness of the proposed approach to increase system capacity while preserving current right-of-ways (ROWs).

Tunable and reversible drug control of protein production via a self-excising degron.

An effective method for direct chemical control over the production of specific proteins would be widely useful. We describe Small Molecule-Assisted Shutoff (SMASh), a technique in which proteins are fused to a degron that removes itself in the absence of drug, leaving untagged protein. Clinically tested HCV protease inhibitors can then block degron removal, inducing rapid degradation of subsequently synthesized protein copies. SMASh allows reversible and dose-dependent shutoff of various proteins in multiple mammalian cell types and in yeast. We also used SMASh to confer drug responsiveness onto a RNA virus for which no licensed inhibitors exist. As SMASh does not require permanent fusion of a large domain, it should be useful when control over protein production with minimal structural modification is desired. Furthermore, as SMASh only involves a single genetic modification and does not rely on modulating protein-protein interactions, it should be easy to generalize to multiple biological contexts.

Cell‐Based Proteome Profiling Using an Affinity‐Based Probe (AfBP) Derived from 3‐Deazaneplanocin A (DzNep)

3-Deazaneplanocin A (DzNep), a global histone methylation inhibitor, has attracted significant interest in epigenetic research in recent years. The molecular mechanism of action and the cellular off-targets of DzNep, however, are still not well-understood. Our aim was to develop novel DzNep-derived small-molecule probes suitable to be used in live mammalian cells for identification of potential cellular targets of DzNep under physiologically relevant settings. In the current study, we have successfully designed, synthesized, and tested one such probe, called DZ-1. DZ-1 is a 'clickable' affinity-based probe (AfBP) derived from DzNep with minimal structural modifications. The probe was found to be highly cell-permeable, and possessed similar anti-apoptotic activities as DzNep in MCF-7 mammalian cells. Two additional control probes were made as negative labeling/pull-down probes in order to minimize false identification of background proteins due to unavoidable, intrinsic nonspecific photo-crosslinking reactions. All three probes were subsequently used for in-situ proteome profiling in live mammalian cells, followed by large-scale pull-down/LC-MS/MS analysis for identification of potential cellular protein targets that might interact with DzNep in native cellular environments. Our LC-MS/MS results revealed some highly enriched proteins that had not been reported as potential DzNep targets. These proteins might constitute unknown cellular off-targets of DzNep. Though further validation experiments are needed in order to unequivocally confirm these off-targets, our findings shed new light on the future use of DzNep as a validated chemical probe for epigenetic research and as a potential drug candidate for cancer therapy.

Deuterated clopidogrel analogues as a new generation of antiplatelet agents.

Clopidogrel (CPG) is an antithrombotic prodrug that needs hepatic cytochrome P450 (CYP) enzymes for its bioactivation. The clinical effects of CPG have been associated with high intersubject variability and a certain level of resistance. Recently, comprehensive biotransformation studies of CPG support that the observed clinical uncertainty stems from the low bioactivation efficiency, which is attributed to extensive attritional metabolism (e.g., hydrolysis of the methyl ester functionality and oxidation of the piperidine moiety). With the goal of potentiating the desired thiophene 2-oxidation through minimal structural modification, we have adopted the strategy of targeted metabolism shift and have designed and synthesized deuterated piperidine analogues of CPG. In vitro studies showed that the prodrug activation percentages have been significantly increased for the deuterated analogues as a result of stability enhancement of the piperidine moiety. In a pharmacological study with a rat model, oral administration of the deuterated analogues also demonstrated higher inhibitory activity than that of CPG against adenosine diphosphate (ADP) induced platelet aggregation. These deuterated analogues represent a new generation of antiplatelet agents with the potential to overcome the major clinical drawbacks of CPG.

Total synthesis, stereochemical elucidation and biological evaluation of Ac2SGL; a 1,3-methyl branched sulfoglycolipid from Mycobacterium tuberculosis

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), continues to represent a challenging pathogen causing many deaths. A reason for the persistence of this pathogen is the cell-envelope composition, which consists of long-tailed (glyco)lipids, involved in the modulation of the host immune response. Diacylated sulfoglycolipid Ac2SGL (1), found in the cell envelope, is a potent antigen that stimulates the immune response towards TB. This observation suggests the application of 1 as part of a vaccine. Here, we report the first asymmetric total synthesis of 1. Two approaches were developed for the synthesis of hydroxyphthioceranic acid (4), its polypropionate part, thereby establishing the absolute stereochemistry of the C17 hydroxyl function to be of (R)-configuration. Subsequently, 4 was regioselectively connected to the trehalose core and after selective sulfation and a final fourfold deprotection step, pure 1 was obtained. The identity of synthetic and natural 1 was confirmed by NMR and mass analysis, Furthermore, synthetic 1 shows identical biological function to 1 and activates CD1b-restricted and Ac2SGL-specific T cells that are highly sensitive to minimal structural modifications of 1 with the same potency. A modeling study is presented to point out the structural features of 1 that are important for binding to the antigen-presenting molecule CD1b and to the T-cell receptor.

The effect of the hydrothermal carbonization process on palm oil empty fruit bunch

Investigations of biomass conversion technologies and processes have been carried out intensively for the past two decades due to the reduction in the availability of landfill, stricter regulations, and increasing awareness of the problem. In this study we have concentrated on a wet-base biomass, in particular a waste stream from the commercial production of palm oil, empty fruit bunch (EFB). This has been converted through a hydrothermal carbonization process (HTC), where lignocellulosic material was converted in a low temperature and pressure environment to a product of increased carbon content offering the prospect of a material with a higher commercial value from an abundant waste stream. A purpose built pressure vessel was used in the presence of excess water at relatively low temperatures (180–220 °C) and saturated water pressures (1–22 MPa). The chemical and physical characteristics of the products were confirmed using elemental analysis, calorific value, SEM, FTIR and GCMS. The carbon value recorded a decrease of the O/C ratio of raw EFB = 0.85 to a HTC processed EFB of 0.55. The surface morphology obtained from SEM showed minimal structural modification of the material although small pores (10–13 μm) were seen on the surface of the HTC processed material. This suggests a processing route that preserves the existing carbohydrate structure whilst increasing its carbon content, which offers a route to complex carbon-rich materials based upon naturally grown carbohydrate materials.

Moth Sex Pheromone Receptors and Deceitful Parapheromones

The insect's olfactory system is so selective that male moths, for example, can discriminate female-produced sex pheromones from compounds with minimal structural modifications. Yet, there is an exception for this “lock-and-key” tight selectivity. Formate analogs can be used as replacement for less chemically stable, long-chain aldehyde pheromones, because male moths respond physiologically and behaviorally to these parapheromones. However, it remained hitherto unknown how formate analogs interact with aldehyde-sensitive odorant receptors (ORs). Neuronal responses to semiochemicals were investigated with single sensillum recordings. Odorant receptors (ORs) were cloned using degenerate primers, and tested with the Xenopus oocyte expression system. Quality, relative quantity, and purity of samples were evaluated by gas chromatography and gas chromatography-mass spectrometry. We identified olfactory receptor neurons (ORNs) housed in trichoid sensilla on the antennae of male navel orangeworm that responded equally to the main constituent of the sex pheromone, (11Z,13Z)-hexadecadienal (Z11Z13-16Ald), and its formate analog, (9Z,11Z)-tetradecen-1-yl formate (Z9Z11-14OFor). We cloned an odorant receptor co-receptor (Orco) and aldehyde-sensitive ORs from the navel orangeworm, one of which (AtraOR1) was expressed specifically in male antennae. AtraOR1•AtraOrco-expressing oocytes responded mainly to Z11Z13-16Ald, with moderate sensitivity to another component of the sex pheromone, (11Z,13Z)-hexadecadien-1-ol. Surprisingly, this receptor was more sensitive to the related formate than to the natural sex pheromone. A pheromone receptor from Heliothis virescens, HR13 ( = HvirOR13) showed a similar profile, with stronger responses elicited by a formate analog than to the natural sex pheromone, (11Z)-hexadecenal thus suggesting this might be a common feature of moth pheromone receptors.

Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications

Sarcoglycanopathies (SGP) are a group of autosomal recessive muscle disorders caused by primary mutations in one of the four sarcoglycan genes. The sarcoglycans (α-, β-, γ-, and δ-sarcoglycan) form a tetrameric complex at the muscle membrane that is part of the dystrophin-glycoprotein complex and plays an essential role for membrane integrity during muscle contractions. We previously showed that the most frequent missense mutation in α-sarcoglycan (p.R77C) leads to the absence of the protein at the cell membrane due to its blockade by the endoplasmic reticulum (ER) quality control. Moreover, we demonstrated that inhibition of the ER α-mannosidase I activity using kifunensine could rescue the mutant protein localization at the cell membrane. Here, we investigate 25 additional disease-causing missense mutations in the sarcoglycan genes with respect to intracellular fate and localization rescue of the mutated proteins by kifunensine. Our studies demonstrate that, similarly to p.R77C, 22 of 25 of the selected mutations lead to defective intracellular trafficking of the SGs proteins. Six of these were saved from ER retention upon kifunensine treatment. The trafficking of SGs mutants rescued by kifunensine was associated with mutations that have moderate structural impact on the protein.