Complementary Functional Groups Research Articles

In Situ Eutectic Formation in a Polymeric Matrix via Hot-Melt Reactive Extrusion and the Use of Partial Least Squares Regression Modeling for Reaction Yield Determination.

There has been a significant volume of work investigating the design and synthesis of new crystalline multicomponent systems via examining complementary functional groups that can reliably interact through the formation of noncovalent bonds, such as hydrogen bonds (H-bonds). Crystalline multicomponent molecular adducts formed using this approach, such as cocrystals, salts, and eutectics, have emerged as drug product intermediates that can lead to effective drug property modifications. Recent advancement in the production for these multicomponent molecular adducts has moved from batch techniques that rely upon intensive solvent use to those that are solvent-free, continuous, and industry-ready, such as reactive extrusion. In this study, a novel eutectic system was found when processing albendazole and maleic acid at a 1:2 molar ratio and successfully prepared using mechanochemical methods including liquid-assisted grinding and hot-melt reactive extrusion. The produced eutectic was characterized to exhibit a 100 °C reduction in melting temperature and enhanced dissolution performance (>12-fold increase at 2 h point), when compared to the native drug compound. To remove handling of the eutectic as a formulation intermediate, an end-to-end continuous-manufacturing-ready process enables feeding of the raw parent reagents in their respective natural forms along with a chosen polymeric excipient, Eudragit EPO. The formation of the eutectic was confirmed to have taken place in situ in the presence of the polymer, with the reaction yield determined using a multivariate calibration model constructed by combining spectroscopic analysis with partial least-squares regression modeling. The ternary extrudates exhibited a dissolution profile similar to that of the 1:2 prepared eutectic, suggesting a physical distribution (or suspension) of the in situ synthesized eutectic contents within the polymeric matrix.

Bulk Heterojunction Solar Cell using Ru Dye Attached PCBM

Ru dye (Z-907) is a crucial photosensitizing material in dye-sensitized solar cells (DSSCs). To enhance the utilization of Ru dye’s photosensitizing properties in bulk heterojunction solar cells, a method was developed to synthesize phenyl-C61- butyric acid methyl ester (PCBM) nanoparticles that are chemically linked to Ru dye. PCBM contains a methoxy (−OCH3) group, whereas Ru dye incorporates a carboxyl group (−COOH) within its molecular structure. By exploiting these complementary functional groups, a successful bond between Ru dye and PCBM was established through an anhydride functional group. The coupling of PCBM with Ru dye results in a modification of the energy levels, yielding lower LUMO (3.8 eV) and HOMO (6.1 eV) levels, compared with the LUMO (3.0 eV) and HOMO (5.2 eV) levels of Ru dye alone. This configuration potentially facilitates efficient electron transfer from Ru dye to PCBM, alongside promoting hole transfer from Ru dye to the conducting polymer. Consequently, the bulk heterojunction solar cells incorporating this Ru dye-PCBM configuration demonstrate superior performance, with an open circuit voltage (Voc) of 0.62 V, short circuit current (Jsc) of 0.63 mA cm−2, fill factor (FF) of 65.6%, and a photovoltaic conversion efficiency (η) of 0.25%.

Mecanisms of the chemical crosslinking to obtain the hydrogels: Synthesis, conditions of crosslinking and biopharmaceutical applications

Hydrogels are three-dimensional polymer matrices with recognized biomedical applications. Chemically crosslinked hydrogels offer greater mechanical stability than physically crosslinked hydrogels due to the covalent bonds between their polymeric chains. The preparation of hydrogels by chemical crosslinking involves three basic components: monomer, initiator and crosslinking agent, which must be present in proportions that do not alter the integrity of the hydrogel. The chemical crosslinking mechanism can be designed from reactions between complementary functional groups, ultraviolet light reactions, radical polymerization, high energy irradiation, among others. In this review, we revisit the chemical crosslinking mechanisms involving synthetic or natural polymers. Finally, biomedical applications of hydrogels are discussed, such as drug delivery, cell culture, tissue engineering, cancer therapy, among others.

Preparation and characterization of dummy template molecularly imprinted polymers coupled with HPLC for selective extraction of spiked cloprostenol from milk samples

This study was conducted to develop a particular sorbent for the selective extraction of the luteolytic drug cloprostenol from milk samples. Cloprostenol's luteolytic activity has been proved in animals, whereas the production of prostaglandins is discussed extensively in the literature, while extraction of cloprostenol is rarely discussed. The major objective was to get sufficient molecularly imprinted polymers (MIPs) for selective extraction and detection of cloprostenol. After a series of experiment, MIPs and their analogues NIPs, were synthesized. In these experiments, radical polymerization with non-covalent interactions has been used to synthesize MIPs and NIPs. Different parameters to determine the optimization conditions such as solvent volume, cross-linker, and template ratio were studied in various sets to get better possible characteristics of MIPs. The HPLC was used to evaluate the retention capacity which ranges from 68.5% to 94.1%. The mechanism of adsorption was studied by the isothermal assay and kinetic studies. The kinetic studies exhibited a high retention capacity within 20 min of MIPs contact. The percentage of polymer yield ranged from 53.5% to 92.3%. HPLC coupled with a UV detector showed the limit of detection and limit of quantification of 30.5 ng/mL and 86.7 ng/mL, respectively, for the determination of analytes from milk samples. The recovery of cloprostenol for all spiked samples of milk was higher than 91.54%. Furthermore, the studies showed that MIPs are specific in the adsorption of cloprostenol compared to its other structural analogues. The outcomes also showed the significance of cross-linker concentration and the amount of solvent during the process of polymerization. These parameters greatly affect the preorganization of complementary functional groups, meanwhile, it creates specific cavities for the targeted drugs.

Supramolecular cocrystals of dispiro-P3N3-dicarboxylic acid: Synthesis, structural characterization and hirshfeld surface analysis

The design of cocrystals for a particular molecule begins with examining that molecule's functional group and selecting a complementary functional group that would generate the foreseeable supramolecular synthons. In this work, the cyclotriphosphazene-based compound Dispiro-P3N3-dicarboxylic acid (L) was identified to produce two cocrystals with two different N-donor compounds such as 4,4′-bipyridine and piperazine by slow evaporation technique. These compounds 1 and 2 were characterized by single-crystal X-ray diffraction, PXRD, FT-IR, NMR, UV–Vis spectroscopy, TG analysis, computational analysis of pKa and Hirshfeld surface analysis. The ΔpKa value of compounds 1 (-0.180) and 2 (0.191) indicates that both are cocrystals in nature. Compounds 1 and 2 have the same triclinic crystal system with space group Pī. X-ray diffraction analysis displays that both compounds were formed with the coformer through complementary hydrogen bonding with an alternating sequence of Dispiro-P3N3-dicarboxylic acid and N-donor compounds. Compound 1 exhibits O-H···N and C-H···O hydrogen bonding interactions between Dispiro-P3N3-dicarboxylic acid and 4,4′-bipyridine that results in the formation of one-dimensional polymeric chains A and B. In addition, the adjacent one-dimensional polymeric chains A and B in compound 1 are further held together by π···π interactions between phenyl groups of Dispiro-P3N3-dicarboxylic acids from two different set of one-dimensional polymeric chains A and B. In compound 2, the recognition between Dispiro-P3N3-dicarboxylic acid and piperazine is established via O-H···N, N-H···O hydrogen bondings and π···π interactions which leads to the formation of one-dimensional polymeric chains. Furthermore, the one-dimensional polymeric chains are interconnected with each other via C-H···N hydrogen bondings which results to the formation of two-dimensional sheet like structure in compound 2. Hirshfeld surface analysis confirmed that the O-H···N hydrogen bondings are major interactions in compound 1; in contrast, N-H···O hydrogen bondings are more prominent interactions than the O-H···N hydrogen bondings in compound 2.

Pore anisotropy in shale and its dependence on thermal maturity and organic carbon content: A scanning SAXS study

Pore orientation in shale governs the fluid transport properties that are key to hydrocarbon production and potential CO2 sequestration. The present work deals with the detailed study of nano-heterogeneities in shales, across the bedding plane, of varying thermal maturity and total organic carbon content using scanning small-angle X-ray scattering (SAXS) experiments. The complementary X-ray Micro-Computed Tomography (μCT) and functional group mapping elucidate the heterogeneity in micrometer resolution. 2D SAXS profiles of the shales show elliptical patterns indicating the nanoscale pore anisotropy in shale. The orientation of pores and their spatial variation is strongly dependent on the content of organic matter. The variance in the anisotropy parameter is validated with chemical mapping and high-resolution 3D imaging.

Preparation of functional and reactive nanosilver nanogels using oxidized carboxymethyl cellulose

The designing of functional and reactive nanosilver has been carried out by in-situ reduction of silver nitrate using oxidized carboxymethyl cellulose (OCMC). The reduction process is also accompanied by the stabilization of nanoparticles using the OCMC polymer chain, leading to the formation of a structure where nanosilver is entrapped within OCMC gel. The silver nanogels characterized using transmission electron microscopy (TEM) are found to be ∼22 nm. By virtue of the presence of dialdehyde functionality around the silver nanogels, they have the ability to react with a polymer having a complementary functional group. The nanogels have exhibited prominent antimicrobial activity against both gram-negative and gram-positive bacteria. It has been observed that a 0.3 mM concentration of silver nanogel is active in inhibiting bacterial growth. The antibacterial activity of the synthesized Ag nanogels was dose-dependent, with 99.9 % of E. coli and S. aureus destroyed within 5 h at a concentration of 0.4 mM Ag nanogels. The nanogels disrupted the bacterial cell wall and generated reactive oxygen species inside the cell, which resulted in cell death. This investigation provides a very interesting application as a coating for biomedical implants and devices.

Coalescence dynamics of nanofluid droplets in T-junction microchannel

The effect of nanoparticles on droplet coalescence in microchannel was investigated experimentally. The interaction between acid-functionalized nanoparticles and polymers with complementary terminal functional groups facilitates the adsorption of particles at the oil–water interface. Three flow patterns were observed: squeezing coalescence, decompression coalescence and non-coalescence. The presence of nanoparticles significantly reduces the droplet coalescence percentage, and stable droplets could be obtained when the particles concentration increased to 1%. Furthermore, it was found that the film drainage time of squeezing coalescence was independent of the nanoparticles concentration. However, the film drainage time of decompression coalescence increases with nanoparticles concentration. Taking the influence of nanoparticles on the film drainage time into consideration, a new prediction model was proposed. Coupling the droplet contact time with the film drainage time, the critical capillary number for droplet coalescence was obtained. This work could provide important data and technical support for the application of nanoparticle-stabilized emulsions.

Lamotrigine Novel Cocrystals: An Attempt To Enhance Physicochemical Parameters

Background: Cocrystals are defined as multiple component structures whose components interact through non-covalent interactions.Cocrystals can enhance other essential properties of the APIs.Aim: The current research work focuses on formulating and evaluating novel co-crystals of Lamotrigine anti-epileptic drug (BCS-II)Methods: The Cocrystals of Lamotrigine drug with different cocrystals formers like Saccharin sodium, 4-Hydroxy benzoic acid, andMethyl paraben used with molar ratios (1:1) were prepared by solvent drop method, co-grinding method, and solvent evaporationmethod.Results: The results signify the establishment of intermolecular interaction within the cocrystals. In the novel cocrystals, Lamotriginewas determined to be engaged in the hydrogen bond interaction with the complementary functional groups of Saccharin sodium, 4-Hydroxy benzoic acid, and methyl paraben. Compared with the pure Lamotrigine flow properties for prepared co-crystal by usingsolvent evaporation method crystals are showing excellent flow properties. LTG-SAC CF I, LTG-HBA I, and LTG-MP III showed49.6 folds, 7.4 folds, and 3.36 folds improved solubility respectively. The dissolution test showed that the LTG-SAC CF I, LTG-HBAI, and LTG-MP III cocrystals exhibited a 1.09-fold, 1.08-fold, and 1.07-fold higher dissolution rate than the pure Lamotrigine.Conclusions: LTG-SAC CF I, LTG-HBA I, and LTG-MP III cocrystals showed modification in the chemical environment,intermolecular interactions were established, improved flow properties with enhanced intrinsic solubility and in-vitro dissolution ratethan pure drug.

Artificial Water Channels—Progress Innovations and Prospects

Artificial Water Channels—Progress Innovations and Prospects

Supertough poly(lactic acid)/bio-polyurethane blends fabricated by dynamic self-vulcanization of dual difunctional monomers

In this work, a facile and efficient strategy known as ‘dynamic self-vulcanization of dual difunctional monomers’ was reported to toughen poly(lactic acid) (PLA) with in-situ formed crosslinked bio-polyurethane (PCPUE) phase from plant oil-derived hydrogenated dimer diol (Pripol) and hexamethylene diisocyanate (HDI). By simply adjusting equivalent ratios (nNCO/nOH) of complementary functional groups between these two difunctional toughening monomers from 1.0 to 2.2 while fixing their total feeding content at 20 wt%, the notched impact strength (IS) and phase morphologies of PLA blends can be tailored in a broad range. When the ratio reached 1.6, the maximum IS value up to 87.1 kJ/m2 (about 28 times that of neat PLA) was achieved with an elongation-at-break of ~223 %. Based on the analysis on reaction mechanism and phase morphologies, the optimum interfacial compatibility between PLA and PCPUE phases in junction with the proper crosslinking density of rubbery PCPUE phase was considered to be responsible for such a remarkable improvement in impact toughness.

Raspberry-Shaped Microgels Assembled at the Oil–Water Interface by Heterocoagulation of Complementary Microgels

Raspberry-shaped particles have attracted increasing interest due to their tunable surface morphologies and physicochemical properties. A variety of covalent and noncovalent strategies have been developed for the fabrication of raspberry-shaped particles. However, most of these strategies are complex or require precise control of solution conditions. In this work, we develop a direct approach for the fabrication of noncovalent raspberry-shaped microgels. Our strategy works through the electrostatically driven heterocoagulation of binary microgels with complementary functional groups at the oil-water interface. By introducing hexanoic acid (HA) into the oil phase, stable inverse water-in-oil (w/o) Pickering emulsions could be stabilized solely by HA-swollen microgels or self-assembled raspberry-shaped microgels. Furthermore, the formation mechanism and the interfacial properties of interfaces laden with raspberry-shaped microgels were investigated. The results indicate that HA can effectively improve the hydrophobicity and interfacial activity of microgels. In addition, raspberry-shaped microgels achieve high coverage on the droplet surface, resulting in the elastic interface and excellent stability of emulsions. We envision that these results will not only fill a knowledge gap in the field of soft matter interfacial self-assembly, but also will shed light on the rational design of raspberry-shaped soft colloids and the on-demand control of interfacial rheology. In addition, we expect that our results will contribute to wider applications of microgel-stabilized emulsions, including cascade catalysis, microreactor, and in vivo drug delivery.

Silicones with different crosslinking patterns: Assessment from the perspective of their suitability for biomaterials

Silicones are one of the most important classes of synthetic biomaterials. In order to become stand-alone objects, they must be cross-linked. This can be achieved by chemical (radical, addition or condensation reactions) or physical (supramolecular interactions) processes, each requiring the presence of complementary functional groups and specific deployment conditions (organic, organo-metallic or metallic often non-removable catalyst, temperature, pressure, UV-irradiation, etc.), and leading to materials with particular characteristics in terms of bulk structure and surface. A number of such model networks have been prepared and evaluated from the perspective of their suitability as biomaterials. After the structural characterization by FT-IR spectroscopy aimed mainly at identifying residual functional groups that could affect their behavior, the samples were subjected to specific tests. Thus, the hydrolytic and enzymatic stability were studied in aqueous environments with different pH values. The surface analysis was done by atomic force microscopy (AFM), which allowed the highlighting of the topography and the estimation of the average roughness. The water, formamide, methylene iodide, and buffer solutions` contact angles, as well as blood interfacial tension were also determined. The biocidal activity against a series of fungi and bacteria was studied. The bio- and mucoadhesion of the films were evaluated by an appropriate technique, and the cell adhesion test was performed on Normal Human Dermal Fibroblasts (NHDF). The results indicate that, regardless of the crosslinking pattern, the films are hydrophobic, hydrolytically stable and biocompatible but bio-/mucoadhesivity are low, which recommends them as sutures and the series crosslinked by addition would be suitable for extrusion processes with “click” crosslinking.

Efficient designing of half-moon-shaped chalcogen heterocycles as non-fullerene acceptors for organic solar cells.

One key strategy to further improve the power conversion efficiency (PCE) of organic solar cells (OSCs) is to incorporate various complementary functional groups in a molecule. Such strategies proved attractive for tuning the photovoltaic performances of the materials and can show a much higher absorption phenomenon with narrower band gaps. Despite the outstanding benefits, materials selection and their efficient modeling is also an extremely challenging job for the development of OSCs materials. In this manuscript, we proficiently developed an efficient series of small molecule-based non-fullerene acceptors (SM-NFAs) SN1-SN9 for OSCs and characterized by density functional theory (DFT) and time-dependent DFT (TD-DFT). The characteristics required to estimate electron and hole mobility, and open-circuit voltage (Voc) were investigated by optimizing the geometrical parameters, absorption spectra, exciton binding energy, frontier molecular orbitals (FMOs), electronic structures, and charge transfer rates. The outcomes of these materials showed that all newly constructed small-molecule-based non-fullerene acceptors exhibit broader and better absorption efficiency (λmax = 761 to 778nm) and exciton dissociation, while much lower LUMO energy levels which may help to enhance the reorganizational energies. Further, a narrow bandgap also offers better photovoltaic properties. Hence, the designed molecules exhibited narrow bandgap values (Eg = 2.82 to 2.98eV) which are lower than that of the reference molecule (3.05eV). High Voc and photocurrent density values with lower excitation and binding energies eventually increase the PCEs of the OSC devices. The obtained results have shown that designed molecules could be effective aspirants for high-performance OSCs.

Maltotriose-based star polymers as self-healing materials

Self-healing polymers with complementary functional groups can spontaneously repair mechanical damage. We developed star-like block copolymers from a naturally-derived maltotriose core with acrylate arms consisting of soft poly(n-butyl acrylate) (PnBA) and hard poly(tert-butyl acrylate) (PtBA) segments, exhibiting self-repair behavior. A facile and efficient two-step synthesis involving a “core-first” approach employed a simplified electrochemically mediated ATRP (seATRP) with only 25 ppm of a copper catalyst. Precise control was maintained during the polymerization of both acrylates, yielding soft and hard segments. Macromolecules with maltotriose core and polymer arms composed of PnBA homopolymer or poly(n-butyl acrylate)-block-poly(tert-butyl acrylate) (PnBA-b-PtBA) block copolymer had a narrow molecular weight distribution (Mw/Mn = 1.13 and 1.17, respectively). Thermomechanical properties of maltotriose-based star-like copolymers and their linear counterpart were studied by thermogravimetry (TGA), differential scanning calorimetry (DCS) and tensile analysis. The star-like polymers exhibited self-healing behavior. A complete repair of the damaged material occurred after 30 min without external intervention under ambient conditions.

Novel Co-crystals and Eutectics of Febuxostat: Characterization, Mechanism of Formation, and Improved Dissolution.

Co-crystallization studies were undertaken to improve the solubility of a highly water-insoluble drug febuxostat (FXT), used in the treatment of gout and hyperuricemia. The selection of co-crystal former (CCF) molecules such as 1-hydroxy 2-naphthoic acid (1H-2NPH), 4-hydroxy benzoic acid (4-HBA), salicylic acid (SAC), 5-nitro isophthalic acid (5-NPH), isonicotinamide (ISNCT), and picolinamide (PICO) was based on the presence of complementary functional groups capable of forming hydrogen bond and the ΔpKa difference between FXT and CCF. A liquid-assisted grinding (LAG) method was successfully employed for the rapid screening of various pharmaceutical adducts. These adducts were characterized based on their unique thermal (differential scanning calorimetry) and spectroscopic (Fourier transform infrared and Raman spectroscopy) profiles. Binary phase diagrams (BPD) were plotted to establish a relationship between the thermal events and adduct formed. Powder X-ray diffraction (PXRD) studies were carried out to confirm the formation of eutectic/co-crystal. Thermogravimetric analysis (TGA) was also performed for the novel co-crystals obtained. The propensity for strong homo-synthons over weak hetero-synthons and strong hetero-synthons over weak homo-synthons during supramolecular growth resulted in the formation of eutectics and co-crystals respectively. FXT:1H-2NPH (1), FXT:4-HBA (1), FXT:SAC (1, 2), and FXT:5-NPH (2-1) gave rise to pure eutectic systems, while FXT:ISNCT (2-1) and FXT:PICO (1) gave rise to novel co-crystals with characteristic DSC heating curves and PXRD pattern. Additionally, the impact of microenvironmental pH and microspeciation profile on the improved dissolution profile of the co-crystals was discussed. Graphical Abstract.

Structural Comparisons of Cefotaximase (CTX-M-ase) Sub Family 1.

The cefotaximase or CTX-M, family of serine-β-lactamases represents a significant clinical concern due to the ability for these enzymes to confer resistance to a broad array of β-lactam antibiotics an inhibitors. This behavior lends CTX-M-ases to be classified as extended spectrum β-lactamases (ESBL). Across the family of CTX-M-ases most closely related to CTX-M-1, the structures of CTX-M-15 with a library of different ligands have been solved and serve as the basis of comparison within this review. Herein we focus on the structural changes apparent in structures of CTX-M-15 in complex with diazabicyclooctane (DABCO) and boronic acid transition state analog inhibitors. Interactions between a positive surface patch near the active site and complementary functional groups of the bound inhibitor play key roles in the dictating the conformations of active site residues. The insights provided by analyzing structures of CTX-M-15 in complex with DABCO and boronic acid transition state analog inhibitors and analyzing existing structures of CTX-M-64 offer opportunities to move closer to making predictions as to how CTX-M-ases may interact with potential drug candidates, setting the stage for the further development of new antibiotics and β-lactamase inhibitors.

Crystal Habit Modification of Metronidazole by Supramolecular Gels with Complementary Functionality

A series of bis(urea) compounds with complementary functional groups similar to the pharmaceutical drug metronidazole and a structural isomer isometronidazole have been synthesized. The gelation properties of these compounds were studied in various solvent/solvent mixtures. The mechanical strength of the isomeric gelators was compared using rheology, and the morphologies of the xerogels were analyzed by scanning electron microscopy. These gels were used as media for metronidazole crystallization resulting in a marked habit modification of the metronidazole crystals in the drug-mimicking gels. However, crystallization in the nonmimetic isomeric gel resulted in morphologies similar to the solution state. These results indicate that the drug-mimetic gels interact with the surface of the drug crystal giving rise to new morphologies.

Controlled Chemical Functionalization toward 3D‐2D Carbon Nanohorn‐MoS2 Heterostructures with Enhanced Electrocatalytic Activity for Protons Reduction

AbstractThe realization of novel heterostructures arising from the combination of nanomaterials is an effective way to modify their physicochemical and electrocatalytic properties, giving them enhanced characteristics stemming from their individual constituents. Interfacing carbon nanohorns (CNHs) possessing high porosity, large specific surface area, and good electrical conductivity, with MoS2 owning multiple electrocatalytic active sites but lacking significant conductivity, robust interactions, and effective structure, can be a strategy to boost the electrocatalytic reduction of protons to molecular hydrogen. Herein, in a stepwise approach, complementary functional groups are covalently introduced at the conical tips and sidewalls of CNHs, along with the basal plane of MoS2, en route the construction of 3D‐2D CNH‐MoS2 heterostructures. The increased MoS2 loading onto CNHs, improving and facilitating charge delocalization and transfer in neighboring CNHs, along with the plethora of active sites, results in excellent electrocatalytic activity for protons reduction, same as that of commercial Pt/C. Minute overpotential is registered, low Tafel slope and small charge‐transfer resistance for electrocatalyzing the evolution of hydrogen from the newly prepared heterostructure of 0.029 V, 71 mV dec−1, and 34.5 Ω, respectively. Furthermore, the stability of the 3D‐2D CNH‐MoS2 heterostructure is validated after performing 10 000 ongoing electrocatalytic cycles.

Emerging small-molecule therapeutic approaches for Alzheimer's disease and Parkinson's disease based on targeting microRNAs.

Emerging small-molecule therapeutic approaches for Alzheimer's disease and Parkinson's disease based on targeting microRNAs.