Hydrogen Bond Donor Research Articles

Domain Swapping in Abiotic Foldamers.

Foldamer sequences that adopt tertiary helix-turn-helix folds mediated by helix-helix hydrogen bonding in organic solvents have been previously reported. In an attempt to create genuine abiotic quaternary structures, i.e. assemblies of tertiary structures, new sequences were prepared that possess additional hydrogen bond donors at positions that may promote an association between the tertiary folds. However, a solid state structure and extensive solution state investigations by Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) show that, instead of forming a quaternary structure, the tertiary folds assemble into stable domain-swapped dimer motifs. Domain swapping entails a complete reorganization of the arrays of hydrogen bonds and changes in relative helix orientation and handedness that can all be rationalized.

Domain Swapping in Abiotic Foldamers

AbstractFoldamer sequences that adopt tertiary helix‐turn‐helix folds mediated by helix‐helix hydrogen bonding in organic solvents have been previously reported. In an attempt to create genuine abiotic quaternary structures, i.e. assemblies of tertiary structures, new sequences were prepared that possess additional hydrogen bond donors at positions that may promote an association between the tertiary folds. However, a solid state structure and extensive solution state investigations by Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) show that, instead of forming a quaternary structure, the tertiary folds assemble into stable domain‐swapped dimer motifs. Domain swapping entails a complete reorganization of the arrays of hydrogen bonds and changes in relative helix orientation and handedness that can all be rationalized.

A new sensitive fluorescence probe based on the molecular recognition for the detection of antipsychotics in human urine

Risperidone, olanzapine and aripiprazole have good efficacy in schizophrenia. Monitoring the concentration of antipsychotics in patients is helpful to provide a precise medication administration. Although many detection techniques based on large instruments have been developed, they are expensive and cumbersome, which are not conducive to clinical promotion. In this paper, rose bengal (RB) was firstly used as a low-cost fluorescent probe for the detection of antipsychotic drugs. Under the condition of pH 3.9, there is a strong negative electrostatic potential region in RB, which attracts positively charged antipsychotic drugs. This property allows the halogen atoms and oxygen atoms of RB to act as hydrogen bond donors to molecularly bond with the H atoms of the antipsychotic drugs, forming a non-luminous complex. The fluorescence intensity showed a linear quench relationship with the increasing concentration of risperidone, olanzapine and aripiprazole with low detection limits of 103, 82.0 and 81.0 μg L−1, respectively. This fluorescent method has good selectivity and can be successfully utilized in detecting antipsychotic medications in human urine and pharmaceutical tablets.

Synthesis Studies and the Evaluation of C6 Raloxifene Derivatives.

Methodology is described for the synthesis of C6 derivatives of raloxifene, a prescribed drug for the treatment and prevention of osteoporosis. Studies have explored the incorporation of electron-withdrawing substituents at C6 of the benzothiophene core. Efficient processes are also examined to introduce hydrogen bond donor and acceptor functionality. Raloxifene derivatives are evaluated with in vitro testing to determine estrogen receptor (ER) binding affinity and gene expression in MC3T3 cells.

Reducing Free Fatty Acids in Crude Palm Oil Using Diethylene Glycol and Zinc(II) Chloride Based Deep Eutectic Solvent

Deep eutectic solvents (DES) were prepared by precise combinations of mol fractions of chemical compounds, resulting in a lowered melting point due to hydrogen bonding. This research aimed to elucidate the physicochemical attributes of DES and its effectiveness in mitigating free fatty acid (FFA) levels in crude palm oil (CPO). Zinc(II) chloride (ZnCl2) served as the hydrogen bond acceptor (HBA) while diethylene glycol (DEG) as the hydrogen bond donor (HBD). Characterization included freezing point, density, viscosity, conductivity, and pH determination. At a ZnCl2 mol fraction of 0.30, the resulting DES exhibited homogeneity with transparent liquid properties, featuring a freezing point below −10 °C, density of 1.42 g/mL, viscosity of 1933.40 cP, conductivity of 66.13 µS/cm, and pH 3.42. FTIR spectra confirmed hydrogen bond interactions between HBA and HBD. Applied to CPO at a 1:1 volumetric ratio (DES:CPO), with 2 h of stirring time at 50 °C, FFA content decreased from 4.11 to 0.86%. This research highlights DES as an environmentally sustainable purification agent, significantly reducing FFA levels in unrefined palm oil.

The medicinal chemistry of piperazines: A review.

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs has also been highlighted to provide a good understanding to researchers for future research on piperazines.

Description and In silico ADME Studies of US-FDA Approved Drugs or Drugs under Clinical Trial which Violate the Lipinski’s Rule of 5

Background & Objective: Christopher A. Lipinski, in 1997, formulated Lipinski’s rule of five for drug-likeness prediction of potent molecules. It states that molecular weight (less than 500 Daltons), octanol/water partition coefficient (not exceeding more than 5), hydrogen bond acceptor (no more than 10), and hydrogen bond donor (no more than 5) are important for good oral bioavailability. Many drugs among various important classes such as antibiotics, anti-cancer, HIV and HCV protease inhibitors, immunosuppressants, cardiovascular, antifungal, and other miscellaneous classes are approved by FDA or other drug regulatory authorities as clinical use lie beyond the rule of five. In this review, beyond the rule of 5 drugs belonging to these classes (which are either currently approved or under clinical study) are explored and their ADME properties are analyzed. Methods: Data of 73 beyond the rule of 5 drugs, belonging to various classes, were collected and their ADME properties were calculated using the Qikprop prediction program of maestro 12.9 module of Schrodinger software. Result: Out of 73 drugs, 4 had at least 1 Rule of 5 (Ro5) violation, 16 had at least 2, 31 had at least 3 out of which 22 drugs had 4, Ro5 violations. Conclusion: Drugs not obeying the rule of five may also serve as good clinical candidates and potential candidates should not be discarded only on the basis of this rule.

Multi-dimensional hydrogen bonds regulated emissions of single-molecule system enabling surficial hydrophobicity/hydrophilicity mapping

Constructing multi-dimensional hydrogen bond (H-bond) regulated single-molecule systems with multi-emission remains a challenge. Herein, we report the design of a new excited-state intramolecular proton transfer (ESIPT) featured chromophore (HBT-DPI) that shows flexible emission tunability via the multi-dimensional regulation of intra- and intermolecular H-bonds. The feature of switchable intramolecular H-bonds is induced via incorporating several hydrogen bond acceptors and donors into one single HBT-DPI molecule, allowing the “turn on/off” of ESIPT process by forming isomers with distinct intramolecular H-bonds configurations. In response to different external H-bonding environments, the obtained four types of crystal/cocrystals vary in the contents of isomers and the molecular packing modes, which are mainly guided by the intermolecular H-bonds, exhibiting non-emissive features or emissions ranging from green to orange. Utilizing the feature of intermolecular H-bond guided molecular packing, we demonstrate the utility of this fluorescent material for visualizing hydrophobic/hydrophilic areas on large-scale heterogeneous surfaces of modified poly(1,1-difluoroethylene) (PVDF) membranes and quantitatively estimating the surface hydrophobicity, providing a new approach for hydrophobicity/hydrophilicity monitoring and measurement. Overall, this study represents a new design strategy for constructing multi-dimensional hydrogen bond regulated ESIPT-based fluorescent materials that enable multiple emissions and unique applications.

On the solubility of azodicarbonamide in water/DMSO mixtures: an experimental and computational study.

This work aims at studying why azodicarbonamide (ADCA), a formally apolar compound with good hydrogen bond (HB) acceptors, is soluble only in polar aprotic solvents like dimethyl sulfoxide (DMSO) but not in water. Solubility measurements, as well as quantum mechanical and classical molecular dynamics simulations, were employed to tackle the problem. We found that in the liquid phase a polar conformer of ADCA (µ = 8.7 D), unreported to date, is favoured under the enthalpic drive provided by a highly polar solvent. At the same time, the very high hydrogen bond propensity of water with itself prevents this solvent from providing an effective hydrogen bond-mediated solvation. Solvents bearing good HB acceptors, while lacking strong HB donors, contribute to further stabilizing solute-solvent adducts through weak and fluxional HBs that involve the amide groups of ADCA. Implications for the solubility of ADCA down to µM concentrations were evaluated, also with the aid of classical simulations of solution nanodroplets.

Role of Deep Eutectic Solvent Precursors as Hydrotropes: Unveiling Synergism/Antagonism for Enhanced Kraft Lignin Dissolution.

Lignin holds significant potential as a feedstock for generating valuable aromatic compounds, fuels, and functional materials. However, achieving this potential requires the development of effective dissolution methods. Previous works have demonstrated the remarkable capability of hydrotropes to enhance the aqueous solubility of lignin, an amphiphilic macromolecule. Notably, deep eutectic solvents (DESs) have exhibited hydrotropic behavior, significantly increasing the aqueous solubility of hydrophobic solutes, making them attractive options for lignin dissolution. This study aimed at exploring the influence of hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) on the performance of DESs as hydrotropes for lignin dissolution, while possible dissolution mechanisms in different water/DES compositions were discussed. The capacity of six alcohols (glycerol, ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol) and cholinium chloride to enhance the solubility of Kraft lignin in aqueous media was investigated. A correlation between solubility enhancement and the alkyl chain length of the alcohol was observed. This was rationalized upon the competition between hydrotrope-hydrotrope and solute-hydrotrope aggregates with the latter being maximized for 1,4-butanediol. Interestingly, the hydrotropic effect of DESs on lignin solubility is well represented by the independent sum of the dissolving contributions from the corresponding HBAs and HBDs in the diluted region. Conversely, in the concentrated region, the solubility of lignin for a certain hydrotrope concentration was always found to be higher for the pure hydrotropes rather than their combined HBA/HBD counterparts.

The Role of the Molecular Encapsulation Effect in Stabilizing Hydrogen-Bond-Rich Gel-State Lithium Metal Batteries.

Gel-state polymer electrolytes with superior mechanical properties, self-healing abilities and high Li+ transference numbers can be obtained by in situ polymerization of monomers with hydrogen-bonding moieties. However, it is overlooked that the active hydrogen atoms in hydrogen-bond donors experience displacement reactions with lithium metal in lithium metal batteries (LMBs), leading to corrosion of the lithium metal. Herein, it is discovered that the addition of hydrogen-bond acceptors to hydrogen-bond-rich gel-state electrolytes modulates the chemical activity of the active hydrogen atoms via the formation of hydrogen-bonded intermolecular interactions. The characterizations reveal that the added hydrogen-bond acceptors encapsulate the active hydrogen atoms to suppress the interfacial chemical corrosions of lithium metals, thereby enhancing the chemical stability of the polymer structure and interphase. With the employment of this strategy, a 1.1 Ah LiNi0.8Co0.1Mn0.1O2/Li metal pouch cell achieves stable cycling with 96.3 % capacity retention at 100 cycles. This new approach indicates a feasible path for achieving in situ polymerization of highly stable gel-state-based LMBs.

Hydrogen bond formation may enhance RDC-based discrimination of enantiomers.

The distinction of enantiomers based on residual anisotropic parameters obtained by alignment in chiral poly-γ-benzyl-L-glutamate (PBLG) is among the strongest in high-resolution NMR spectroscopy. However, large variations in enantiodifferentiation among different solutes are frequently observed. One hypothesis is that the formation of hydrogen bonds between solute and PBLG is important for the distinction of enantiomers. With a small set of three almost spherical enantiomeric pairs, for which 1DCH residual dipolar couplings are measured, we address this issue in a systematic way: borneol contains a single functional group that can act as a hydrogen bond donor, camphor has a single group that may act as a hydrogen bond acceptor, and quinuclidinol can act as both hydrogen bond donor and acceptor. The results are unambiguous: although camphor shows low enantiodifferentiation with PBLG and alignment that can be predicted well by the purely steric TRAMITE approach, the distinction of enantiomers for the other enantiomeric pairs is significantly higher with alignment properties that must involve a specific interaction in addition to steric alignment.

Advanced NADES-based extraction processes for the recovery of phenolic compounds from Hass avocado residues: A sustainable valorization strategy

Natural Deep Eutectic Solvents (NADES) are eco-friendly solvents with considerable potential for extracting bioactive compounds. In this study, we aimed to extract phenolic compounds from Hass avocado residues (epicarp and seed) using NADES in combination with ultrasound-assisted extraction (UAE) and pressurized liquid extraction (PLE) as advanced processes. Ten eutectic mixtures, consisting of choline chloride (ChCl) or betaine as hydrogen bond acceptors (HBA), as well as fructose (Fru), glucose, lactic acid (Lac), citric acid, or glycerol as hydrogen bond donors (HBD), were prepared through stirring and heating. The estimated values for total phenol content (TPC), proanthocyanidin content (PAC), monomeric anthocyanin content (MAC), and antioxidant capacity of the extracts demonstrated a noticeable influence of these solvents. The PLE process significantly enhanced the extraction of phenolic compounds from the epicarp, as evidenced by TPC (185 ± 9 mg gallic acid equivalent/g dry sample) and PAC (77.8 ± 6 mg proanthocyanidin B2/g dry sample) values. Phytochemical characterization conducted via HPLC-QTOF-MS/MS revealed the great extraction capacity of ChCl:Fru and ChCl:Lac, and the improvement of extraction efficiency through PLE. The results suggest that employing these innovative solvents along with advanced extraction processes, especially under high pressures, provides a sustainable approach to recover extracts with high content of phenolic compounds from Hass avocado agro-industrial waste, thus enabling their valorization.

Cholinium Pyridinolate Ionic Pair-Catalyzed Fixation of CO2 into Cyclic Carbonates.

A halide-free ionic pair organocatalyst was proposed for the cycloaddition of CO2 into epoxide reactions. Cholinium pyridinolate ionic pairs with three different substitution positions were designed. Under conditions of temperature of 120 °C, pressure of 1 MPa CO2, and catalyst loading of 5 mol %, the optimal catalyst cholinium 4-pyridinolate ([Ch]+[4-OP]-) was employed. After a reaction time of 12 h, styrene oxide was successfully converted into the corresponding cyclic carbonate, and its selectivity was improved to 90%. A series of terminal epoxides were converted into cyclic carbonates within 12 h, with yields ranging from 80 to 99%. The proposed mechanism was verified by 1H NMR and 13C NMR titrations. Cholinium cations act as a hydrogen bond donor to activate epoxides, and pyridinolate anions combine with carbon dioxide to form intermediate carbonate anions that attack epoxides as nucleophiles and lead to ring opening. In summary, a halide-free ionic pair organocatalyst was designed and the catalytic mechanism in the cycloaddition of CO2 into epoxides reactions was proposed.

Ultrasound-assisted extraction of sulfonamides from soil samples using natural deep eutectic solvents and their determination by liquid chromatography tandem mass spectrometry

In this work, several potential natural deep eutectic solvents (NADES) were evaluated as sustainable solvents in the development of an ultrasound (US)-assisted extraction method for sulfonamides from soil samples and final determination by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Choline chloride (ChCl) was used as hydrogen bond acceptor (HBA), and different carboxylic acids and alcohols were tested as hydrogen bond donors (HBDs) in different molar ratios in order to find the optimum combination able to form appropriated NADES for the extraction of sulfonamides. Among the different mixtures tested, the one consisting of ChCl:1,3-propanediol in a molar ratio of 1:4 showed the better physico-chemical properties and was selected for the US-assisted extraction of sulfonamides. Under optimum conditions, no matrix effect was observed and quantitative recoveries, ranging from 81.9 % to 103.9 % with relative standard deviations (RSDs) lower than 8 % were obtained, reaching limits of quantification within the range 8.5–31 µg Kg−1, depending upon the analyte. In addition, after evaluation by AGREEprep, Sample Preparation Metric of Sustainability (SPMS) and Blue Applicability Grade Index (BAGI) metrics tools, the proposed method was found to be superior to other published methods in terms of safety and environmental impact with good applicability potential.

Study of the experimental and microscopic mechanism of the removal of phenolic compounds from wastewater based on hydrophobic deep eutectic solvents

Dephenolisation has been a key environmental concern; therefore, separating and recycling phenolic compounds from wastewater can reduce environmental harm and the consumption of resources, respectively. Herein, we selected three hydrogen bond acceptors (HBAs) and three hydrogen bond donors (HBDs) with excellent industrial prospects, which were widely sourced, and combined them as nine hydrophobic deep eutectic solvents (HDESs) to perform liquid–liquid extraction (LLE) experiments and molecular simulation studies on model wastewaters containing phenol and catechol. The preliminary screening of HDESs was carried out by conducted with quantum chemical simulations using σ-Profiles, and the microscopic mechanism of the extraction process using HDESs was analysed through molecular dynamics (MD) simulations based on radial distribution function, spatial distribution function, mean square displacement and interaction energy results. Guided by the above molecular simulation results, experimental studies on LLE using HDESs were further conducted to determine the optimal conditions of the experimental operation, including the types and ratios of HBAs and HBDs, feed ratios between the HDESs and model wastewater, and extraction temperatures. The experimental studies revealed that the extraction efficiency of octanoic acid − geraniol (molar ratio 1:3) on a 0.6 % (mass concentration) phenol and catechol model wastewater at 25℃ could reach > 96 %. Moreover, the results were consistent with that of MD simulation. The above methodologies provide a reliable basis for resolving similar problems.

Deep eutectic solvent pretreatment of sugarcane bagasse for efficient lignin recovery and enhanced enzymatic hydrolysis

This study explores the sugarcane bagasse (SCB) pretreatment with two deep eutectic solvents (DESs) prepared from choline chloride (ChCl) as a hydrogen bond acceptor (HBA) to two hydrogen bond donors (HBD): oxalic acid (OA) and trifluoroacetic acid (TFA) for lignin recovery and enhancing enzymatic saccharification. The pretreatment conditions, reaction time, temperature, and DES concentration were optimized using response surface methodology. The two DESs showed a lignin yield of 74.67 ± 2.75 and 83.50 ± 2.65 mg per gm of SCB, respectively. Enzymatic hydrolysis of the cellulose-enriched material (CEM) obtained after pretreatment showed an enhanced RS yield of around 4-fold compared to the untreated SCB. The CEM was characterized using FTIR, Powder X-ray diffraction, and Scanning Electron Microscopy. The recovered lignin characteristics were studied using FTIR, 1H NMR, and 2D-HSQC NMR analysis. The FTIR spectra of lignin show the presence of aromatic skeletal vibrations, -OH, -CH, C-O stretching vibration, and aromatic C-H deformation. Furthermore, the pretreatment solvent recyclability studies were conducted to evaluate the effectiveness of DES for a sustainable biorefinery process.

Effect of alkaline deep eutectic solvents pretreatment on CH4 yield from anaerobic digestion of corn stover

Deep eutectic solvents (DES), comprising hydrogen bond donors (HBD) and acceptors (HBA), are gaining prominence in biomass pretreatment due to their excellent lignin depolymerization capabilities. This study explored the impact of alkaline DES pretreatment, specifically focusing on CH4 yield from corn stover anaerobic digestion. Batch experiments were conducted to assess the influence of ethylene glycol (EG) concentration, pretreatment time, and organic loading rate (OLR) on CH4 yield. Results indicated that these factors markedly affected the cumulative CH4 yield. Subsequent optimization using Box-Behnken design (BBD) significantly enhanced the CH4 yield by 1.16 times, achieving the optimal conditions at 0.4 v/v EG concentration, 33.8 min of pretreatment, and 22.2 w/v OLR. Notably, DMER64 and Methanobacterium emerged as the dominant bacterial and archaeal communities, constituting 40.2 % and 71.9 % respectively. Spearman correlation analysis underscored that enhanced substrate accessibility fostered a hydrogen-based, CH4-producing synergistic metabolic pathway. Alkaline DES pretreatment notably resulted in 20.5 % of the carbon flow being directed to CH4, demonstrating its efficacy in converting corn stover into a viable clean energy source and mitigating the environmental impact of agricultural waste.

КОНФОРМАЦИОННЫЕ СВОЙСТВА И ЭЛЕКТРОННАЯ СТРУКТУРА ПРОТИВООПУХОЛЕВОГО АГЕНТА TYR-SER-LEU

Molecular modeling methods were used to study the features of the spatial and electronic structure of the antitumor tripeptide YSL (Tyr-Ser-Leu), developed by Chinese scientists. The conformational analysis of the molecule revealed a limited set of its energetically preferable conformational states in a certain range of relative energy. The nature of the forces stabilizing the low-energy conformations of the tripeptide molecule was determined. As a result of the study, the energetically preferable ranges of dihedral angles, the energy contributions of interresidual interactions and hydrogen bonds, as well as the mutual arrangement of residues and their side chains in low-energy conformations of the tripeptide were also determined. Using the methods of molecular mechanics, the energy contributions of intramolecular interactions in low-energy conformational states of the molecule were obtained. Based on quantum-chemical calculations, the distribution of electron density and the values of dipole moments of the most optimal spatial structures of the YSL tripeptide molecule were determined. The reactivity of the tripeptide was also studied by quantum chemical calculations based on the obtained electronic characteristics of each low-energy conformation of the molecule. Using the calculated coordinates of the atoms of the energetically preferable structures of the molecule, their molecular models were built, the comparison of which makes it possible to identify the structural criteria necessary to create a drug suitable for clinical use.

Effects of hydrogen bond donors on PVDF membrane modification using choline chloride-based deep eutectic solvents

Deep eutectic solvents (DESs) were investigated as promising candidates in modifications towards hydrophobic polyvinylidene fluoride (PVDF) membranes based on its hydrophilic and hygroscopic properties. Five choline chloride-based DESs with various hydrogen bond donor (HBD) components were investigated as PVDF membrane modifiers by blending it with the membrane dope solution at 2 wt%. The incorporation of DESs appeared to influence the structure and morphology of the membranes, where macrovoid formations were suppressed and the formation of thin, densely porous skin layers were promoted as observed through SEM imaging. DES incorporation showed effects in contact angle reduction of the PVDF membranes from 90.22° to 60.07°, indicating hydrophilic modifications. Additionally, modifications with DESs yielded improvements in membrane flux (62.49 L/m2·h using glycerol-HBD) and protein solute rejection (74.62 % using glucose-HBD), though the overall tensile strength of the membranes were decreased from 4.24 MPa to the lowest value of 2.92 MPa. Ultimately, DESs were shown to be significant pore-forming agents in altering the morphology of PVDF membranes, and improving the thermal stability. Among the five tested DESs, PVDF modified with glycerol-HBD DES yielded the best membrane parameters and performances. DESs were demonstrated as prospective membrane modifiers in inducing hydrophilicity and influencing membrane morphology.