Charge-assisted Hydrogen Bonds Research Articles

Influence of protonation on the geometry of 2-{[(2,6-dimethylphenoxy)ethyl]amino}-1-phenylethan-1-ol: crystal structures of the free base and of its chloride and 3-hydroxybenzoate salt forms.

The aroxyalkylaminoalcohol derivatives are a group of compounds known for their pharmacological action. The crystal structures of four new xylenoxyaminoalcohol derivatives having anticonvulsant activity are reported, namely, 2-{[2-(2,6-dimethylphenoxy)ethyl]amino}-1-phenylethan-1-ol, C18H23NO2, 1, the salt N-[2-(2,6-dimethylphenoxy)ethyl]-1-hydroxy-1-phenylethan-2-aminium 3-hydroxybenzoate, C18H24NO2+·C7H5O3-, 2, and two polymorphs of the salt (R)-N-[2-(2,6-dimethylphenoxy)ethyl]-1-hydroxy-1-phenylethan-2-aminium chloride, C18H24NO2+·Cl-, 3 and 3p. Both polymorphs crystallize in the space group P21212 and each has two cations and two anions in the asymmetric unit (Z'= 2). The molecules in the polymorphs show differences in their molecular conformations and intermolecular interactions. The crystal packing of neutral 1 is dominated by intermolecular O-H...N hydrogen bonds, resulting in the formation of one-dimensional chains. In the crystal structures of the salt forms (2, 3 and 3p), each protonated N atom is engaged in a charge-assisted hydrogen bond with the corresponding anion. The protonation of the N atom also influences the conformation of the molecular linker between the two aromatic rings and changes the orientation of the rings. The crystal packing of the salt forms is dominated by intermolecular O-H...O hydrogen bonds, resulting in the creation of chains and rings. Structural studies have been enriched by the calculation of Hirshfeld surfaces and the corresponding fingerprint plots.

Structure directing roles of weak noncovalent interactions and charge-assisted hydrogen bonds in the self-assembly of solvated podands: an example of an anion-assisted dimeric water capsule

A 4-aminopyridinium-functionalized mesitylene-based podand could facilitate the formation of a dimeric capsular assembly due to the complementary hydrogen bonding mediated by bromide counterions and lattice water.

Selectivity considerations of host compound trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic acid when presented with pyridine and picoline mixtures: charge-assisted versus classical hydrogen bonding

Stereoview showing strong intermolecular charge-assisted hydrogen bonds between host, and host and guest, molecules accounting for the host preference for 2MP (and 3MP). Disfavoured guests PYR and 4MP experienced only weaker classical hydrogen bonding interactions.

Enhancement of charge-assisted hydrogen bond capabilities due to O-alkylation proximity in alkoxy cationic polythiophenes: solution- and solid-state evidence via EPR, AFM and surface free energy.

Despite the array of applications for cationic polythiophenes (CPTs), there is still a need for structure-function guidelines and mechanistic understanding of their solution- and solid-state properties. This work presents a solution- and solid-state investigation of the effect of O-alkylation proximity on the hydrogen bonding (H-bonding) capabilities of alkoxy-CPTs, based on comparing an imidazolium alkoxy CPT with strong cation-pi, pi+ and positive charge-assisted hydrogen bonding (+CAHB) capabilities (PIMa), with two isothiouronium alkoxy CPTs with two-point +CAHB capabilities (PT1 & PT2), which have short and long alkoxy side chains, respectively. Our results show that a closer proximity of O-alkylation strengthens the +CAHB capabilities of PT1: in aqueous solutions, PT2 aggregates have a stronger interaction with cationic EPR spin probes than aggregates of PIMa and PT1, which in turn show a similar extent of repulsion towards the cationic spin probes. In solid-state, atomic force microscopy (AFM) shows that PIMa generates dendritic structures onto mica, with features of diffusion-limited aggregation (DLA), indicating strong interactions with the anionic substrate due to a high configurational entropy during spreading, regardless of being drop-casted from water or 1,4-dioxane-water (W-DI), despite the latter disturbing H-bonding due to selective solvation. PT1 is also capable of generating dendritic structures resembling ballistic aggregation (BA). However, this occurs only when casting from water, since W-DI generates island-like aggregates resembling attachment limited aggregation (ALA), which is the morphology generated by PT2 regardless of the solvent. Finally, spin-coated films of PIMa and PT1 show similar dispersivity of the surface free energy (SFE), which in turn is larger than that in PT2 films, which are also more affected when casted from W-DI, presenting much larger decreases of dispersivity. These results constitute a novel empirical structure-function guideline that could be useful for optimal design and/or processing of alkoxy CPTs. For example, dendritic patterns have recently gained attention since the colloidal droplet drying is related to engineering applications including inkjet printing, biosensing, and functional material design, while the SFE is relevant for opto- and bio-electronic applications of conjugated polyelectrolytes (CPEs). This information could also be useful when analyzing previous results obtained from alkoxy CPTs with different side chain lengths.

Facile route for synthesis of Fe0/Fe3C/γ-Fe2O3 carbon composite using hydrothermal carbonization of sugarcane bagasse and its use as effective adsorbent for sulfamethoxazole removal

Non-toxic mesoporous magnetic carbon composite was synthesised from hydrothermal carbonization of sugarcane bagasse with Iron (III) nitrate nonahydrate in two steps along with thermo-chemical oxidation process using sodium hydroxide. IR spectrum exposed the presence of oxygenated functional groups and FeO whereas XRD analysis revealed the availability of Fe0/Fe3C/γ-Fe2O3 at varying intensities. SEM analysis showed the spherical shaped carbon is well encapsulated with iron particles. Textural studies showed that after thermo-chemical activation intensified the surface area on composites to about 491.474 m2 g−1 thereby, promoting improved porosity on the carbon matrix. The fabricated composite showed magnetization of 32.84 emu g−1 and SMX adsorption capacity as 169.49 mg g−1. Kinetics and isotherm studies revealed that removal of SMX fitted well in Pseudo-second order and Langmuir models. The mode of interaction of SMX on magnetic carbon composites with respect to different pH was studied showing that π-π electron donor interaction (EDA), hydrophobic interaction, charge assisted hydrogen bond formation were responsible for SMX removal. The selectivity nature of magnetic composite with respect to SMX was studied in the presence of multiple pollutant. Use of magnetic carbon helps in industrialising the material to high level due to their unique property in separation and recycling. Application of hydrothermal carbonization is found to be applicable for wet solid substance thereby evolving structural carbon compound.

Synthesis of aspirin catalyzed by supramolecular compound based on Keggin-Type phosphomolybates with flexible 1,3-bis(4-pyridyl)propane

With an aim to catalyze the synthesis of aspirin in a green approach, an unreported supramolecular compound [H3(C13H14N2)2][PMo12O40] (PMo12O40-Bpp) based on Keggin-type has been regarded as catalyst in synthesis of aspirin, which is prepared with flexible 1,3-bis(4-pyridyl)propane (C13H14N2, Bpp) and characterized structurally. Structural analysis of X-ray single crystal diffraction reveals that charge-assisted hydrogen bonds (CAHBs) N+-H…O- is formed between N+ of protonated Bpp molecule in PMo12O40-Bpp as hydrogen bond donor and molybdenum phosphate oxide cluster anion [PMo12O40]3-, and 3D supramolecular framework with porous is connected by intermolecular hydrogen bonds C9-H9…O3, C11-H11…O3 and C6-H6…O7 alternatively. When reactants of pharmaceutical esterification are salicylic acid and acetic anhydride, by screening dose of catalyst PMo12O40-Bpp, temperature and reaction time, the optimal conditions are determined as follows: 0.15 g PMo12O40-Bpp (mass fraction 5%), 90 °C and 55 min. Under these conditions, the yield of aspirin, the conversion rate of salycilic acid and the selectivity of catalyst can reach up to 69.24%, 98.02% and 70.64%, which indicating that catalytic activity is similar to that of concentrated sulfuric acid (85%) under the same reaction conditions. The kinetic results of pharmaceutical esterification of aspirin catalyzed by PMo12O40-Bpp show that reaction order is 1.37, rate constant is 1.13 × 10-3 k/L·(mol·s)-1, and apparent activation energy is 64.39 kJ·mol−1. After PMo12O40-Bpp catalyzes pharmaceutical esterification of aspirin repeatedly, PXRD, IR and lifetime of catalyst show that structure of PMo12O40-Bpp is unchanged and catalytic activity does not decrease significantly, indicating that PMo12O40-Bpp can be recycled for multiple times. Above experimental results may be due to specific “pseudo-liquid phase” phenomenon of POM-based supramolecular compounds to make full contact with reactants in the catalytic process, further stabilizing carbocation intermediates effectively through [PMo12O40]3- with greater surface electronegativity, which is more conducive to attack of hydroxyl oxygen atom on salicylic acid to promote pharmaceutical esterification reaction of aspirin catalyzed by PMo12O40-Bpp. This successful work implies that POM-based supramolecular compounds as catalysts in pharmaceutical synthetic process have potential to reduce environmental pollution and provide newfangled inspirations for green pharmaceutical chemistry.

Assembly of two pharmaceutical salts of sparfloxacin with pyrocatechuic acid: Enhancing in vitro antibacterial activity of sparfloxacin by improving the solubility and permeability

With the purpose of improving the solubility and permeability of sparfloxacin (SPX) to enhance the antibacterial activity in vitro, two unreported pharmaceutical salts including a salt with pyrocatechuic acid (PCA) containing methanol, and another salt with PCA without methanol, namely, SPX-PCA-MeOH (C19H23F2N4O3·C7H5O4·CH4O·H2O) and SPX-PCA (C19H23F2N4O3·C7H5O4), were synthesized and structure characterized. Comprehensive crystal structures, molecular electrostatic potential and Hirshfeld surface analysis reveal that in the two pharmaceutical salts of SPX prepared, the protons of carboxylic moiety groups on the coformer were transferred to the nitrogen atom of the SPX piperazine ring, and the SPX was ionized from neutral to form charge assisted hydrogen bonds (+) CAHBs (N+-H···O) to construct a stable crystal structure. By forming pharmaceutical salts, the equilibrium solubility order of two pharmaceutical salts of SPX and pure SPX is SPX-PCA>SPX-PCA-MeOH>SPX, and the order of permeability is SPX-PCA>SPX-PCA-MeOH>SPX. Preliminary structure-activity relationships speculate that the SPX and PCA rely on CAHBs to form pharmaceutical salts, which makes SPX change from neutral to ionized, resulting in the increase of the solubility of SPX. The increased permeability of the two pharmaceutical salts of SPX may be attributed to the combination of the N atom of the piperazine ring of SPX and the hydroxyl group of the PCA molecule by CAHBs, which reduces the number of polar sites in the system and thus reduces the hydrophilicity and increases hydrophobicity of the pharmaceutical salt of SPX, therefore creating condition for the transmembrane transport. Meanwhile, the antibacterial activities in vitro of two pharmaceutical salts of SPX are improved, when compared with the corresponding parent compound (SPX), which change the order is consistent with the solubility and permeability. This implies that the introduction of solvent molecules may play a minimal role in improving the physicochemical properties of the active pharmaceutical ingredients. Further to this, it is surprising that the hygroscopic stabilities of two pharmaceutical salts of SPX were significantly improved compared with that of pure SPX.

Interaction of Microplastics with Antibiotics in Aquatic Environment: Distribution, Adsorption, and Toxicity

As two major types of pollutants of emerging concerns, microplastics (MPs) and antibiotics (ATs) coexist in aquatic environments, and their interactions are a source of increasing concern. Therefore, this work examines the interaction mechanisms of MPs and ATs, and the effect of MPs on ATs bioavailability and antibiotic resistance genes (ARGs) abundance in aquatic environments. First, the mechanisms for ATs adsorption on MPs are summarized, mainly including hydrophobic, hydrogen-bonding, and electrostatic interactions. But other possible mechanisms, such as halogen bonding, CH/π interaction, cation-π interaction, and negative charge-assisted hydrogen bonds, are newly proposed to explain the observed ATs adsorption. Additionally, environmental factors (such as pH, ionic strength, dissolved organic matters, minerals, and aging conditions) affecting ATs adsorption by MPs are specifically discussed. Moreover, MPs could change the bioaccumulation and toxicity of ATs to aquatic organisms, and the related mechanisms on the joint effect are reviewed and analyzed. Furthermore, MPs can enrich ARGs from the surrounding environment, and the effect of MPs on ARGs abundance is evaluated. Finally, research challenges and perspectives for MPs-ATs interactions and related environmental implications are presented. This review will facilitate a better understanding of the environmental fate and risk of both MPs and ATs.

Halogen and Hydrogen Bond Motifs in Ionic Cocrystals Derived from 3-Halopyridinium Halogenides and Perfluorinated Iodobenzenes.

Four halopyridinium salts, 3-chloro- and 3-bromopyridinium chlorides and bromides, have been successfully cocrystallized with two ditopic perfluorinated iodobenzenes, 1,4-diiodotetrafluorobenzene and 1,2-diiodotetrafluorobenzene. These halogen bond donor molecules were chosen because the different positionings of halogen bond donor atoms can lead to different supramolecular architectures. In this work, we present insight into the halogen bond acceptor potential of chloride and bromide ions, as well as the halogen bond donor potential of chlorine and bromine atoms substituted on the pyridinium ring when combined with the expectedly very strong hydrogen bonds between halopyridinium ions and free halogenide anions. A series of eight cocrystals were obtained in which three pairs of isostructural cocrystals were formed. Dominant interactions in the obtained cocrystals were charge-assisted hydrogen bonds between halopyridinium cations and halogenide ions as well as halogen bonds between halogen atoms on the pyridinium ring and halogenide ions.

A Water Soluble Pd2 L4 Cage for Selective Binding of Neu5Ac.

The sialic acid N‐acetylneuraminic acid (Neu5Ac) and its derivatives are involved in many biological processes including cell‐cell recognition and infection by influenza. Molecules that can recognize Neu5Ac might thus be exploited to intervene in or monitor such events. A key obstacle in this development is the sparse availability of easily prepared molecules that bind to this carbohydrate in its natural solvent; water. Here, we report that the carbohydrate binding pocket of an organic soluble [Pd2L4]4+ cage could be equipped with guanidinium‐terminating dendrons to give the water soluble [Pd2L4][NO3]16 cage 7. It was shown by means of NMR spectroscopy that 7 binds selectively to anionic monosaccharides and strongest to Neu5Ac with K a=24 M−1. The cage had low to no affinity for the thirteen neutral saccharides studied. Aided by molecular modeling, the selectivity for anionic carbohydrates such as Neu5Ac could be rationalized by the presence of charge assisted hydrogen bonds and/or the presence of a salt bridge with a guanidinium solubilizing arm of 7. Establishing that a simple coordination cage such as 7 can already selectively bind to Neu5Ac in water paves the way to improve the stability, affinity and/or selectivity properties of M2L4 cages for carbohydrates and other small molecules.

Structural insight into the fiber dyeing ability: Pyridinium arylazo pyridone dyes

Herein, we report the synthesis and characterization of nine 6-hydroxy-4-methyl-3-pyridinium-2-pyridone based azo dyes, wherein, eight of them being novel. Used building blocks ensured water solubility of six dyes and made them adequate to be used for dyeing in an alkaline environment contrary to the traditional application of arylazo pyridone dyes. The peculiarity of the compounds arises as they exhibit zwitterion-hydrazone equilibrium and shift from neutral to cationic dyes. It is shown that the equilibrium strongly depends on the electronic effects of the p-substituent in the phenyl moiety, as well as, pH values of the solutions. The screening of the dyeing process (by using multifiber fabric) suggested that synthesized compounds are most eligible for dyeing wool and diacetate fabrics at a pH of 8.5. Furthermore, 100% wool and diacetate fabrics were dyed and used for the dyeing assessment. A comprehensive study between dye architectures and fiber dyeing was performed. The interplay of various interactions, responsible for the dye-fiber binding, has been proposed, bearing in mind both, dyes' and fibers’ structures and pH dependency. Namely, dye-wool interactions are mostly based upon charge assisted hydrogen bonds, wherein these interactions are strengthened by C–H···π contact when dyes are affixed to diacetate. The specific nature of the dye is affected by the electronic effect of the p-substituents of the phenyl moiety, upon which, a detailed study on fibers affinity towards zwitterionic and/or hydrazone forms has been outlined. Most of the dyed fabrics exhibit good to excellent ultraviolet protection, while dyed diacetate shows good washing fastness.

Elucidation of Charge Contribution in Iridium-Chelated Hydrogen-Bonding Systems

We present two iridium complexes 1H + and 2H + that contain cationic ligands to extend the knowledge of charge-assisted hydrogen bonding (CAHB), which counts among the strongest non-covalent bonding interactions. Upon protonation, both complexes were converted into new hydrogen-bonding arrays with various selectivity for respective H-bonding partners. This study compares the association strengths of four hydrogen-bonding co-systems, emphasizing the roles of CAHB in supramolecular systems. We determined that the cationic charge in these systems contributed up to 2.7 kJ mol−1 in the H-bonding complexation processes.

Halide-modulated self-assembly of metal-free perovskite single crystals for bio-friendly X-ray detection

Halide-modulated self-assembly of metal-free perovskite single crystals for bio-friendly X-ray detection

A novel crystalline molecular salt of sulfamethoxazole and amantadine hybridizing antiviral-antibacterial dual drugs with optimal in vitro/vivo pharmaceutical properties

In order to exploit the advantages to the full of multidrug salification strategy in amending the pharmaceutical properties of drugs both in vitro and in vivo, and further to open up a new way for its applications in bacteria-virus mixed cross-infection drugs, a novel dual-drug crystalline molecular salt hybridizing antibacterial drug sulfamethoxazole (SFM) with antiviral ingredient amantadine (ATE), namely SFM-ATE, is successfully designed and synthesized via multidrug salification strategy oriented by proton exchange reaction. The crystal structure of the firstly obtained molecular salt is precisely identified by employing single-crystal X-ray diffraction and multiple other techniques. The results show that, in the crystal lattice of molecular salt SFM-ATE, the classical hydrogen bonds together with charge-assisted hydrogen bonds contribute to two- dimensional networks, between which the hydrophobic interaction plays an important role. The relevant in vitro/vivo pharmaceutical properties of the dual-drug molecular salt are carried out through a comparative investigation of theoretical and experimental methods. It has been found that SFM displays concurrent improvements over the bulk drug in its permeability and dissolution after forming the molecular salt, which is supported by the molecular electrostatic potential calculation and Hirshfeld surface analysis. Encouragingly, the perfected in vitro biopharmaceutical properties can effectually turn into the in vivo pharmacokinetic preponderances with the expedited peak plasma concentration, lengthened half-life and enhanced bioavailability. Better yet, the antibacterial activities of SFM from the molecular salt get stronger with enlargement in inhibition areas and reduction in values of minimum inhibitory concentrations against the tested bacterial strains. Consequently, the present contribution not only supplies an opportunity for widening applications for classical sulfa drugs via dual-drug salification strategy, but also offers an alternative approach in dealing with viral-bacterial coinfection even other complex diseases by drugs’ hybridization at the molecular level.

The molecular design of drug-ionic liquids for transdermal drug delivery: Mechanistic study of counterions structure on complex formation and skin permeation

Though ionic liquids (ILs) as novel enhancers had garnered wide attention, detailed studies elucidating molecular design of drug-ILs were missing and mechanisms of their formation and skin permeation were still lacking. Herein, we systematically investigated effects of counterions structures on formation and skin permeation of drug-ILs. Firstly, effects of counterions on formation of drug-ILs were dependent on polarizability, molecular weight (M.W.) and polar surface area of counterions. It was caused by strong charge assisted hydrogen bond and van der Waals interactions revealed through FT-IR, X-ray photoelectron spectroscopy and molecular docking, which undermined ionic interactions and reduced total interaction strength, thereby produced lower lattice energy. Then, skin permeability of drug-ILs had a good parabola relationship with M.W., polarizability and log P of counterions. The underlying mechanism was the increased drug miscibility with stratum corneum, which caused conformational disorder and phase transition of lipid bilayers characterized by ATR-FTIR, DSC and confocal laser scanning microscopy. Finally, the drug-ILs proved to be non-irritating using in vivo skin erythema analysis. In conclusion, the quantitative structure-activity relationship models based on counterions structure to predict formation and skin permeation of drug-ILs were developed, which provided basic theory for design of drug-ILs with high permeation-enhancing efficiency.

Mechanically robust amino acid crystals as fiber-optic transducers and wide bandpass filters for optical communication in the near-infrared

Organic crystals are emerging as mechanically compliant, light-weight and chemically versatile alternatives to the commonly used silica and polymer waveguides. However, the previously reported organic crystals were shown to be able to transmit visible light, whereas actual implementation in telecommunication devices requires transparency in the near-infrared spectral range. Here we demonstrate that single crystals of the amino acid L-threonine could be used as optical waveguides and filters with high mechanical and thermal robustness for transduction of signals in the telecommunications range. On their (00bar 1) face, crystals of this material have an extraordinarily high Young’s modulus (40.95 ± 1.03 GPa) and hardness (1.98 ± 0.11 GPa) for an organic crystal. First-principles density functional theory calculations, used in conjunction with analysis of the energy frameworks to correlate the structure with the anisotropy in the Young’s modulus, showed that the high stiffness arises as a consequence of the strong charge-assisted hydrogen bonds between the zwitterions. The crystals have low optical loss in the O, E, S and C bands of the spectrum (1250−1600 nm), while they effectively block infrared light below 1200 nm. This property favors these and possibly other related organic crystals as all-organic fiber-optic waveguides and filters for transduction of information.

Crystal structure of tofacitinib dihydrogen citrate (Xeljanz®), (C16H21N6O)(H2C6H5O7)

The crystal structure of tofacitinib dihydrogen citrate (tofacitinib citrate) has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Tofacitinib dihydrogen citrate crystallizes in space group P212121 (#19) with a = 5.91113(1), b = 12.93131(3), c = 30.43499(7) Å, V = 2326.411(6) Å3, and Z = 4. The crystal structure consists of corrugated layers perpendicular to the c-axis. Within the layers, cation⋯anion and anion⋯anion hydrogen bonds link the fragments into a two-dimensional network parallel to the ab-plane. Between the layers, there are only van der Waals contacts. A terminal carboxylic acid group in the citrate anion forms a strong charge-assisted hydrogen bond to the ionized central carboxylate group. The other carboxylic acid acts as a donor to the carbonyl group of the cation. The citrate hydroxy group forms an intramolecular charge-assisted hydrogen bond to the ionized central carboxylate. Two protonated nitrogen atoms in the cation act as donors to the ionized central carboxylate of the anion. These hydrogen bonds form a ring with the graph set symbol R2,2(8). The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).

Selective adsorption of ofloxacin and ciprofloxacin from a binary system using lignin-based adsorbents: Quantitative analysis, adsorption mechanisms, and structure-activity relationship

A series of actinia-shaped lignin-based adsorbents (LNAEs) featuring lignin (LN) as the core and grafted poly(acrylic acid) (PAA) as the tentacle were designed and fabricated. Two fluoroquinolones (FQs) with similar molecular structures, ofloxacin (OFL) and ciprofloxacin (CIP), were used as targets to study the selective adsorption performance of LNAEs associated with the structural effects of the LN-based adsorbents in FQs binary aqueous system. The adsorption of the two FQs by LNAEs complied with the competitive Langmuir isothermal model, and showed selective removal of CIP over OFL due to the additional negative charge-assisted hydrogen bond (CAHB) formed between the carboxyl group of LNAEs and the secondary amino group of CIP, in addition to the effects of electrostatic attraction and normal hydrogen bonds, according to quantitative studies and density functional theory analysis. A binary nonlinear model based on phenomenological theory was applied to study the effects of PAA branched-chain length and distribution on the selective adsorption performance of the LN-based adsorbents. Accordingly, the branched-chain distribution played a more important role and higher distribution density of branched PAA could expose more adsorption sites on LNAEs' surface and improve the adsorptive selectivity. This study offers a well understanding of the structure–activity relationship of the surface grafting-modified adsorbents in binary pollutant systems and fundamental guidance for the exploitation and design of novel and efficient adsorbents.

Pharmaceutical salt and salt hydrates of vortioxetine with sulfonic acid to ameliorate the solubility and hygroscopicity via the charge-assisted hydrogen bond assembly

Salt forms of vortioxetine (VOT) with three sulfonic acids have been designed and prepared in 1 : 1 stoichiometry ratio, and their crystal structures and physicochemical properties have also been characterized in detail.

Inspiration for revival of old drugs: improving solubility and avoiding hygroscopicity of pipemidic acid by forming two pharmaceutical salts based on charge-assisted hydrogen bond recognitions

Improving solubility and avoiding hygroscopicity of pipemidic acid by forming pharmaceutical salts based on CAHBs.