Highly ordered aggregation of soy protein isolate particles for enhanced gel-related properties through konjac glucomannan addition.

This study assessed the effect of konjac glucomannan (KGM) on the aggregation of soy protein isolate (SPI) and its gel-related structure and properties. Raman results showed that KGM promoted the rearrangement of SPI to form more ß-sheets, contributing to the formation of an ordered structure. Atomic force microscopy, confocal laser scanning microscopy, and small-angle X-ray scattering results indicated that KGM reduced the size of SPI particles, narrowed their size distribution, and loosened the large aggregates formed by the stacking of SPI particles, improving the uniformity of gel system. As the hydrogen bonding between the KGM and SPI molecules enhanced, a well-developed network structure was obtained, further reducing the immobilized water's content (T22) and increasing the water-holding capacity (WHC) of SPI gel. Furthermore, this gel structure showed improved gel hardness and resistance to both small and large deformations. These findings facilitate the design and production of SPI-based gels with desired performance.

Binding and distribution regularity of water molecules in high-moisture textured Antarctic krill (Euphausia superba) meat.

High-moisture extrusion technique with the advantage of high efficiency and low energy consumption is a promising strategy for processing Antarctic krill meat. Consequently, this study aimed to prepare high-moisture textured Antarctic krill meat (HMTAKM) with a rich fiber structure at different water contents (53 %, 57 %, and 61 %) and to reveal the binding and distribution regularity of water molecules, which is closely related to the fiber structure of HMTAKM and has been less studied. The hydrogen-bond network results indicated the presence of at least two or more types of water molecules with different hydrogen bonds. Increasing the water content of HMTAKM promoted the formation of hydrogen bonds between the water molecules and protein molecules, leading to the transition of the ß-sheet to the α-helix. These findings offer a novel viable processing technique for Antarctic krill and a new understanding of the fiber formation of high-moisture textured proteins.

Theoretical study on intramolecular hydrogen bonds of flavonoid cocrystals.

This study investigates the role of intramolecular hydrogen bonds in the formation of cocrystals involving flavonoid molecules, focusing on three active pharmaceutical ingredients (APIs): chrysin (CHR), isoliquiritigenin (ISO), and kaempferol (KAE). These APIs form cocrystals with different cocrystal formers (CCFs) through intramolecular hydrogen bonding. We found that disruption of these intramolecular hydrogen bonds leads to decreased stability compared to molecules with intact bonds. The extrema of molecular electrostatic potential surfaces (MEPS) show that flavonoid molecules with disrupted intramolecular hydrogen bonds have stronger hydrogen bond donors and acceptors than those with intact bonds. Using the artificial bee colony algorithm, dimeric structures of these flavonoid molecules were explored, representing early-stage structures in cocrystal formation, including API-API, API-CCF, and CCF-CCF dimers. It was observed that the number and strength of dimeric interactions significantly increased, and the types of interactions changed when intramolecular hydrogen bonds were disrupted. These findings suggest that disrupting intramolecular hydrogen bonds generally hinders the formation of cocrystals. This theoretical study provides deeper insight into the role of intramolecular hydrogen bonds in the cocrystal formation of flavonoids.

Fast Production of Covalent Organic Frameworks for Covalent Enzyme Immobilization with Boosted Enzymatic Catalysis by Solar-Driven Photothermal Effect.

Developing new enzyme-immobilization systems to stabilize their dynamic structures and meanwhile enhance their catalytic activity is of great significance but very challenging. Herein, we design and fabricate a class of robust mesoporous covalent organic frameworks (COFs) via Michael addition-elimination reaction. It is found that highly crystalline COFs can be produced in 10 min, which is attributed to the promoting effect of the intramolecular hydrogen bond activation. The COFs rich in hydroxyl groups can be facilely post-modified by epibromohydrin to covalently immobilize enzymes with both high loading and activity. Furthermore, we create a solar-driven photothermal-promoted strategy by introducing photoactive azo groups to COF carriers, which can boost the enzyme catalytic performance (lipase) with much higher conversion of various racemic substrates and chiral resolution upon solar light irradiation. The heterogeneous biocatalysts also demonstrate exceptional reusability and stability. This work provides a green and energy-efficient approach to facilitate the scale application of enzyme-immobilized biocatalysts.

Structural characterization of green fluorescent protein in the I-state.

Green fluorescent protein (GFP) is widely utilized as a fluorescent tag in biochemical fields. Whereas the intermediate (I) state has been proposed in the photoreaction cycle in addition to the A and B states, until now the structure of I has only been estimated by computational studies. In this paper, we report the crystal structures of the I stabilizing variants of GFP at high resolutions where respective atoms can be observed separately. Comparison with the structures in the other states highlights the structural feature of the I state. The side chain of one of the substituted residues, Val203, adopts the gauche- conformation observed for Thr203 in the A state, which is different from the B state. On the other hand, His148 interacts with the chromophore by ordinary hydrogen bonding with a distance of 2.85 Å, while the weaker interaction by longer distances is observed in the A state. Therefore, it was indicated that it is possible to distinguish three states A, B and I by the two hydrogen bond distances Oγ-Thr203···Oη-chromophore and Nδ1-His148···Oη-chromophore. We discuss the characteristics of the I intermediate of wild-type GFP on the bases of the structure estimated from the variant structures by quantum chemical calculations.

Fast Collective Hydrogen-Bond Dynamics in Hexafluoroisopropanol Related to its Chemical Activity.

Using fluorinated mono-alcohols, in particular hexafluoro-isopropanol (HFIP), as a solvent can enhance chemical reaction rates in a spectacular manner. Previous work has shown evidence that this enhancement is related to the hydrogen-bond structure of these liquids. Here, we investigate the hydrogen-bond dynamics of HFIP and compare it to that of its non-fluorinated analog, isopropanol. Ultrafast infrared spectroscopy show that the dynamics of individual hydrogen-bonds is about twice as slow in HFIP as in isopropanol. Surprisingly, from dielectric spectroscopy we find the opposite behavior for the dynamics of hydrogen-bonded clusters:  collective rearrangements are 3 times faster in HFIP than in isopropanol. This difference indicates that the hydrogen-bonded clusters in HFIP are smaller than in isopropanol. The differences in cluster size can be traced to changes in the hydrogen-bond donor and acceptor strengths upon fluorination. The smaller cluster size can boost reaction rates in HFIP by increasing the concentration of reactive, terminal OH-groups of the clusters, whereas the fast collective dynamics can increase the rate of formation of hydrogen bonds with the reactants. The longer lifetime of the individual hydrogen bonds in HFIP can enhance the stability of the hydrogen-bonded clusters, and so increase the probability of reactant-solvent hydrogen bonding.

Dual-Hydrogen Bond Donor-Functionalized Carbon Nanotube Fibers: Enhancing Anion-Sensing Performance Through Functionalization Approaches.

In this study, chemiresistive anion sensors are developed using carbon nanotube fibers (CNTFs) functionalized with squaramide-based dual-hydrogen bond donors (SQ1 and SQ2) and systematically compared the sensing properties attained by two different functionalization methods. Model structures of the selectors are synthesized based on a squaramide motif incorporating an electron-withdrawing group. Anion-binding studies of SQ1 and SQ2 are conducted using UV-vis titrations to elucidate the anion-binding properties of the selectors. These studies revealed that the chemical interaction with acetate (AcO-) induced the deprotonation of both SQ1 and SQ2. Selectors are functionalized onto the CNTFs using either covalent or non-covalent functionalization. For covalent functionalization, SQ1 is chemically formed on the surface of the CNTFs, whereas SQ2 is non-covalently functionalized to the surface of the CNTFs assisted by poly(4-vinylpyridine). The results showed that non-covalently functionalized CNTFs exhibited a 3.6-fold higher sensor response toward 33.33 mm AcO- than covalently functionalized CNTFs. The selector library is expanded using diverse selectors, such as TU- and CA-based selectors, which are non-covalently functionalized on CNTFs and presented selective AcO--sensing properties. To demonstrate on-site and real-time anion detection, anion sensors are integrated into a sensor module that transferred the sensor resistance to a smartphone via wireless communication.

A salt from biologically active compounds pyridine-2,3-dicarboxylic (quinolinic) acid and cytosine.

Biologically active compounds are highly sought-after materials for developing novel structures applicable to industry. Cytosine and pyridine-2,3-dicarboxylic acid (quinolinic acid) are notably significant environmentally. Cytosine, a pyrimidine derivative, features a six-membered ring with a ketone and an amino group, constituting a fundamental nitrogenous base found in deoxyribonucleic acid (DNA). The present synthesis yielded a salt of dipyridine-2,3-dicarboxylic acid with cytosine, wherein a proton was transferred from a carboxyl group of quinolinic acid to a ring N atom in the cytosine molecule giving the salt 6-amino-2-oxo-2,3-dihydropyrimidin-1-ium 3-carboxypyridine-2-carboxylate, C4H6N3O+·C7H4NO4-. A Hirshfeld surface analysis was conducted to examine the contribution of contacts within the salt. The structure of the salt was compared to other structures containing quinolinic acid in the Cambridge Structural Database (CSD).

A Molten Alkali Approach to Tailor Hydroxyl Groups of Hexaazatrinaphthalene Toward High-Capacity and Low-Potential Anode of Aqueous Proton Batteries.

Hexaazatrinaphthalene (HATN) has attracted a lot of attention in aqueous proton batteries (APBs). However, its redox potential as an anode is insufficiently negative. The introduction of electron-donating substituent groups, such as hydroxyl groups, is considered as a good approach to reduce the redox potential of HATN. Nevertheless, manufacturing hydroxyl-substituted HATN (HATN-OH) requires either expensive precursors or multi-step process, limiting their research. Herein, a straightforward strategy is proposed to synthesize HATN-OH based on the nucleophilic substitution reaction of halogenated HATN in a molten alkali. The redox potential of 1,2,7,8,13,14-hexahydroxy-5,6,11,12,17,18-hexaazatrinaphthalene (34-HATN-6OH) electrode may be lowered by 0.15 V in comparison to HATN, and exhibits a high specific capacity, low redox potential, remarkable rate capability, and outstanding long-term cycling performance. The electrochemical redox kinetics is significantly enhanced owing to the formation of rapid proton transport channels created by intermolecular hydrogen bond network. The assembled MnO2||34-HATN-6OH full battery delivers a high discharge voltage (1.16 V) and cycling stability (74% capacity retention after 5000 cycles). This study provides a general cost-effective molten alkali approach for the synthesis of hydroxyl-substituted conjugated small molecules from their halogenated counterparts and further enriches the regulation means of electro-chemical performances of organic electrodes for enabling high-capacity and high-voltage APBs.

Hydrogen bonding network in the electrical double layer mediates fast proton skipping to Get Rid of Fenton reaction pH dependence enables highly efficient alkaline water purification.

A fundamental scientific quandary in environmental has always been the pH dependence in Fenton reaction, that is, the reaction kinetics decreases by approximately 1-3 orders of magnitude upon transitioning from an acidic to an alkaline state. Here, we discovered that protons significantly contribute to the Fenton reaction through an examination of the reaction's interfacial behavior characteristics. Proton transfer mediated by hydrogen bond network connectivity in the electric double layer is responsible for the pH dependence of Fenton reaction kinetics. On this basis, the surface potential of Fenton reaction catalyst was modified to optimize the distribution of H2O in the electrical double layer, enhancing the connectivity of the interfacial hydrogen bond network and providing a fast channel for rapid proton transfer. The consecutive hydrogen bond network mediates rapid proton hopping, increasing the proton concentration in the Helmholtz layer, and consequently promoting the proton conductivity from 5.38×10-7 S·cm-2 to 4.35×10-6 S·cm-2 in alkaline conditions for Fenton reaction. Meanwhile, the kinetics reaction rate was improved 20 times, and the pH dependence was reduced from 70.9 % to 12.6 %. This discovery clarifies the key role of the interfacial hydrogen bond network and proton transfer in Fenton reaction kinetics pH dependence. It provides new theories and methods for achieving alkaline high Fenton reaction kinetics.

Local potential energy density - A DFT analysis and the local binding energy in complexes with multiple interactions.

A recently developed method, so-called local potential energy density, LPED, provides the binding energy density of intra/intermolecular interactions. The LPED cannot directly give the binding energy of intra/intermolecular interactions. However, it can indirectly give the binding energy through the linear equation between LPED and supramolecular binding energy, SME. In addition, the LPED can be used to obtain the SME of local or individual interactions indirectly for the case of complexes with multiple interactions, which cannot be obtained for any other method to our knowledge. The calculation of the LPED was evaluated with three different levels of theory using density functional methods. The linearity of LPED and SME between the reference level of theory (ωB97X-D/aug-cc-pVTZ) and the other levels of theory are similar among the studied levels of theory. In addition, LPED was used indirectly to obtain the local binding energy of intermolecular interactions of complexes with multiple interactions, such as the EDTA-Ca+2 and the fosfomycin-Ca+2.

Scalable, High-Yield Monolayer MXene Preparation from Multilayer MXene for Many Applications.

MXene (Ti3C2Tx) is renowned for its exceptional conductivity and hydrophilicity; however, the low yield of monolayers hinders its industrial scalability. Herein, we present a strategy to substantially enhance the monolayer yield by disrupting the hydrogen-bonding cage confinement of multilayer MXene using high-temperature ultrasound, challenging the conventional belief that monolayer MXene can only be prepared at lower temperatures. At approximately 70 °C, the weakened hydrogen bonding between the oxygen-containing terminal groups of multilayer MXene and surrounding water molecules weakens the hydrogen-bond cage confinement. This enables ultrasonic cavitation to generate more microbubbles that penetrate the interlayers of multilayer MXene, resulting in gentle and thorough delamination into larger monolayer nanosheets. Achieving up to a 95% yield in just tens of minutes, these nanosheets exhibit properties comparable to those produced by traditional ice-bath methods. Furthermore, the high-concentration MXene ink produced on a large scale using this high-yield approach exhibits excellent printing and processing capabilities, and the corresponding products showcase superior infrared stealth and Joule heating characteristics. This work addresses a key technical bottleneck in MXene production, paving the way for its extensive technological and industrial applications.

Epidermal growth factor-incorporated hydrogen bond crosslinked hemostatic microparticles capable of timely response to accidental bleeding for prehospital rescue.

Prehospital rescue of accidental massive bleeding is crucial for saving lives. However, currently available hemostatic materials are still in infancy in treating accidental bleeding due to the challenges in fully satisfying the complex outdoor hemostatic requirements. Herein, we designed an epidermal growth factor (EGF)- incorporated, microparticle-formed, high-strength, dynamic environment-stable hemostatic gel system for prehospital rescue. Carboxyl and dimethylamide were employed as the hydrogen bond (H-bond) groups and were carefully engineered into the microparticles (DHMs). We demonstrated that the unique H-bond crosslinked micronized structure enabled the DHM-based gelling system to adequately meet the outdoor hemostatic requirements. The stable H-bond groups allow the DHMs to be stored at room temperature and be easily carried around. The small sizes (150-250 µm) of the DHMs enabled the filling of irregular defects, and upon encountering water, these DHMs integrated into hydrogels (DHMs-gels) with high mechanical strength (1.61 MPa), strong tissue adhesiveness (66.5 kPa) and stable performance under dynamic environments. In vivo results showed that the EGF-incorporated DHMs-gels (DHMs-EGF gel) achieved a 100 % survival rate in a simulated rescue process and promoted wound healing. Simultaneously possessing multiple prehospital rescue-required properties, the hemostatic DHMs-EGF may become an effective tool for emergency rescue.

Effect of non-covalent interactions on the stability and structural properties of 2,4-dioxo-4-phenylbutanoic complex: a computational analysis.

CONTEXT: The 2,4-dioxo-4-phenylbutanoic acid (DPBA) is a subject of interest in pharmaceutical research, particularly in developing new drugs targeting viral and bacterial infections. Complexation with metal ions can improve the stability and solubility of organic compounds. The present study uses quantum chemical calculations to explore the structural and electronic results arising from the interaction between the metal cation (Fe2+) and the π-system of DPBA in different solvents. For this purpose, the analyses of atoms in molecules (AIM) and natural bond orbital (NBO) are employed to comprehend the interaction features and the charge delocalization during the process of complexation. The results demonstrate that the strongest/weakest interactions are evident when the complex is situated in non-polar/polar solvents, respectively. In addition, the investigated complex exhibits two intramolecular hydrogen bonds (IMHBs) characterized by the O-H···O motif. The results indicate that the HBs present in the complex fall within the category of weak to medium HBs. Moreover, the O-H···O HBs are influenced by cation-π interactions, which can increase/decrease their strength in polar/non-polar solvents. To enhance understanding of the interactions above, an examination is conducted on various physical properties including the energy gap, electronic chemical potential, chemical hardness, softness, and electrophilicity power. METHOD: All calculations are conducted within the density functional theory (DFT) using the ωB97XD functional and 6-311 + + G(d,p) basis set. The computations are performed using the quantum chemistry package GAMESS, and the obtained results are visualized by employing the GaussView program.

Synthesis, Physicochemical Characterization, and Antimicrobial Evaluation of Halogen-Substituted Non-Metal Pyridine Schiff Bases.

Four synthetic Schiff bases (PSB1 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4,6-dibromophenol], PSB2 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4,6-diiodophenol], PSB3 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4-iodophenol], and PSB4 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4-chloro-6-iodophenol]) were fully characterized. These compounds exhibit an intramolecular hydrogen bond between the hydroxyl group of the phenolic ring and the nitrogen of the azomethine group, contributing to their stability. Their antimicrobial activity was evaluated against various Gram-negative and Gram-positive bacteria, and it was found that the synthetic pyridine Schiff bases, as well as their precursors, showed no discernible antimicrobial effect on Gram-negative bacteria, including Salmonella Typhi (and mutant derivatives), Salmonella Typhimurium, Escherichia coli, and Morganella morganii. In contrast, a more pronounced biocidal effect against Gram-positive bacteria was found, including Bacillus subtilis, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus haemolyticus. Among the tested compounds, PSB1 and PSB2 were identified as the most effective against Gram-positive bacteria, with PSB2 showing the most potent biocidal effects. Although the presence of reactive oxygen species (ROS) was noted after treatment with PSB2, the primary mode of action for PSB2 does not appear to involve ROS generation. This conclusion is supported by the observation that antioxidant treatment with vitamin C only partially mitigated bacterial inhibition, indicating an alternative biocidal mechanism.

Crystal structure, Hirshfeld surface analysis, and calculations of inter-molecular inter-action energies and energy frameworks of 1-[(1-hexyl-1H-1,2,3-triazol-4-yl)meth-yl]-3-(1-methyl-ethen-yl)-benzimidazol-2-one.

The benzimidazole moiety in the title mol-ecule, C19H25N5O, is almost planar and oriented nearly perpendicular to the triazole ring. In the crystal, C-H⋯O hydrogen bonds link the mol-ecules into a network structure. There are no π-π inter-actions present but two weak C-H⋯π(ring) inter-actions are observed. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (62.0%), H⋯C/C⋯H (16.1%), H⋯N/N⋯H (13.7%) and H⋯O/O⋯H (7.5%) inter-actions. Evaluation of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated via the dispersion energy contributions in the title compound.

Crystal structure and Hirshfeld surface analysis of tri-chlorido-(1,10-phenanthroline-κ2 N,N')phenyltin(IV).

The title compound, [Sn(C6H5)Cl3(C12H8N2)], which was obtained by the reaction between 1,10-phenanthroline and phenyl-tin trichloride in methanol, exhibits intra-molecular hydrogen-bonding inter-actions involving the chlorine and hydrogen atoms. Crystal cohesion is ensured by inter-molecular C-H⋯Cl hydrogen bonds, as well as Y-X⋯π and π-stacking inter-actions involving three different aromatic rings with centroid-centroid distances of 3.6605 (13), 3.9327 (14) and 3.6938 (12) Å]. Hirshfeld surface analysis and the associated two-dimensional fingerprint plots reveal significant contributions from H⋯H (30.7%), Cl⋯H/H⋯Cl (32.4%), and C⋯H/H⋯C (24.0%) contacts to the crystal packing while the C⋯C (6.2%), C⋯Cl/Cl⋯C (4.1%), and N⋯H/H⋯N (1.7%) inter-actions make smaller contributions.

Hydrogen-Bond-Assisted Electrocatalytic Semi-Oxidation of 5-Hydroxymethylfurfural into 2,5-Diformylfuran by Operando Dissociated N-Oxyl Mediator.

The conversion of 5-hydroxymethylfurfural (HMF) to 2,5-diformylfuran (DFF) is a promising approach for enhancing biomass utilization. Nevertheless, traditional methods using noble metal catalysts face challenges due to high costs and poor selectivity towards DFF. Herein, we developed a novel catalytic electrode integrating N-hydroxyphthalimide (NHPI) into a metal-organic framework on a hydrophilic carbon cloth. This design significantly enhances the selective adsorption of HMF due to stronger hydrogen-bond interaction between the electrode's hydrophilic surface and the C(sp3)-OH group in HMF compared to the C(sp2)=O in DFF. Additionally, the electro-driven dissociation of the NHPI-linker generates stabilized N-Oxyl radicals that promote selective semi-oxidation of HMF under neutral conditions. As a result, this approach achieves a high yield rate of 138.2 mol molcat-1 h-1 with a selectivity of 96.7% for the HMF-to-DFF conversion. This work introduces a novel strategy for designing catalytic electrodes with stabilized N-Oxyl radicals, and offers a promising method for electrocatalytic DFF synthesis, leveraging hydrogen-bond interaction between electrode surface and HMF.

Hagfish-inspired hydrogel for root caries: A multifunctional approach including immediate protection, antimicrobial phototherapy, and remineralization.

Root caries is the main cause of oral pain and tooth loss in the elderly. Protecting root lesions from environmental disturbances, resisting pathogens, and facilitating remineralization over time are essential for addressing root caries, but are challenging due to the irregular root surface and the complex oral environment. Hagfish secretes slime when facing danger, which converts into gels upon contact with seawater, suffocating the predators. Inspired by hagfish's defense mechanism, a fluid-hydrogel conversion strategy is proposed to establish a mechanical self-regulating multifunctional platform for root caries treatment. The fluid system (silk fibroin-tannic acid-black phosphorene-urea, ST-BP-U), in which urea disrupts the hydrogen bonds between silk fibroin and tannic acid, can easily spread on the irregular root surface and permeate into dentinal tubules. Upon contact with the surrounding water, urea diffuses, prompting the hydrogel re-formation and creating intimate attachments with micromechanical inlay locks. Meanwhile, BP increases the crosslinking of the re-formed hydrogel network, resulting in reinforced cohesion for robust wet adhesion to the tooth root. This process establishes a structured platform for effective antimicrobial phototherapy and dentin remineralization promotion. This water-responsive fluid-hydrogel conversion system adapts to the irregular root surface in the dynamic wet environment, holding promise for addressing root caries. STATEMENT OF SIGNIFICANCE: Root caries bring a heavy burden to the aging society, but the irregular root surface and dynamic moist oral environment always hinder non-surgical therapeutic effects. Here, we propose a water-responsive fluid-hydrogel conversion strategy aimed at mechanical self-regulation on the irregular and wet root interface to construct a functional structural platform. The liquid system (ST-BP-U) that prebreak intermolecular hydrogen bonds can easily spread on irregular surfaces and dentin tubules. When encountering water, hydrogen bonds re-form, and BP increases the crosslinking of the hydrogel formed in situ. Based on this firm wet-adhesion platform, it provides powerful phototherapy effects and promotes dentin remineralization. This fluid-hydrogel conversion system turns the disadvantages of wet environment into advantages, offering a promising strategy for root caries.

Machine-Learning-Assisted Design of Deep Eutectic Solvents Based on Uncovered Hydrogen Bond Patterns.

Non-ionic deep eutectic solvents (DESs) are non-ionic designer solvents with various applications in catalysis, extraction, carbon capture, and pharmaceuticals. However, discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES formation. The search for DES relies heavily on intuition or trial-and-error processes, leading to low success rates or missed opportunities. Recognizing that hydrogen bonds (HBs) play a central role in DES formation, we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning (ML) models to discover new DES systems. We first analyze the HB properties of 38 known DES and 111 known non-DES systems using their molecular dynamics (MD) simulation trajectories. The analysis reveals that DES systems have two unique features compared to non-DES systems: The DESs have ① more imbalance between the numbers of the two intra-component HBs and ② more and stronger inter-component HBs. Based on these results, we develop 30 ML models using ten algorithms and three types of HB-based descriptors. The model performance is first benchmarked using the average and minimal receiver operating characteristic (ROC)-area under the curve (AUC) values. We also analyze the importance of individual features in the models, and the results are consistent with the simulation-based statistical analysis. Finally, we validate the models using the experimental data of 34 systems. The extra trees forest model outperforms the other models in the validation, with an ROC-AUC of 0.88. Our work illustrates the importance of HBs in DES formation and shows the potential of ML in discovering new DESs.