Formation Of Intramolecular Hydrogen Bond Research Articles

Simultaneous Determination of the Position and Cis-Trans Configuration of Lipid C═C Bonds via Asymmetric Derivatization and Ion Mobility-Mass Spectrometry.

The position and cis-trans configuration of C═C bonds in unsaturated lipids significantly affect their biological activities. Simultaneous identification of the position and cis-trans configuration of C═C bonds in unsaturated lipids is important; nonetheless, it still remains a challenging task. Herein, a stereoselective asymmetric reaction was used to recognize cis-trans isomers of the C═C bonds, and the derivatized precursor ions and product ions were subjected to tandem ion mobility-mass spectrometry (IM-MS) analysis. The theoretical calculation revealed that the formation of intramolecular hydrogen bonds after the cyclization reaction amplified the structural difference between diastereomers and increased the separation efficiency in IM. Consequently, a simple, sensitive, and highly selective platform for simultaneous determination of the position and cis-trans configuration of various C═C bonds in unsaturated lipids was established. It was then successfully applied to pinpoint the cis-trans geometry conversion of the located C═C bonds in lipids of the bacterial membrane under environmental stress and track the heterogeneous distribution of unsaturated lipids in rats after spinal cord injury. The present study also offers new insights into the application of IM-MS technology in resolving molecular structures and demonstrates the potential as a platform for a broad range of applications.

The Role of the Nitro Group on the Formation of Intramolecular Hydrogen Bond in the Methyl Esters of 1-Vinyl-Nitro-Pyrazolecarboxylic Acids

All reactions involving the nitrogen atom in 3(5)-substituted pyrazoles inevitably lead to a mixture of N-substituted 3- and 5- isomers due to tautomerism. The position of substituent can affect the behavior of N-vinyl isomers, in particular, the ability of some functional groups to form =C-H...O or =C-H...N weak hydrogen bonding type interaction with α-hydrogen of vinyl group due to steric reasons. Moreover, the additional substituents in the pyrazole ring can further influence the possibility and nature of specific intramolecular interactions. Here we have shown the effect of the nitro group on the formation of hydrogen bonds in methyl esters of 1-vinyl-4-nitro-3(5)- and 1-vinyl-5-nitro-3(5)-pyrazole carboxylic acids. A comprehensive study, including synthesis, quantum chemical calculations, NMR and XRD analysis, allowed to conclude that, contrary to expected, in the methyl ester of 1-vinyl-4-nitro-5-pyrazolecarboxylic acid, the formation of a planar conformation is unfavorable, preventing formation of a classical hydrogen bond. On the other hand, there is a hydrogen bond between the nitro group and vinyl group in 1-vinyl-5-nitro-pyrazolecarboxylic acids.

Exploring boratrane's potential to enhance the thermal stability of phenol-formaldehyde resins by borate bridge as a crosslinker and the mechanistic formation of boron species in carbonaceous materials: A comprehensive study

In advanced material science, we explore the potential of boratrane, a promising agent for enhancing thermal stability. By combining rigorous Density Functional Theory (DFT) calculations with groundbreaking experimental analyses, we reveal the intricate interplay of radical intermediates and mechanisms underlying the thermal evolution of boratrane-infused materials. Our innovative approach illuminates dynamic structural transformations and elucidates boratrane's pivotal role in fortifying thermal resilience. The DFT calculations identify radical intermediates and mechanisms of thermal degradation, highlighting the role of borate bridges in delocalizing π-electrons in aromatic rings through Gibbs free energy (∆GRXN), Highest Occupied Molecular Orbital (HOMO), Lowest Unoccupied Molecular Orbital (LUMO), and electrostatic potential (ESP) analyses. Fukui function analysis provides insights into the reactivity of these structures towards free radical attacks. Our findings demonstrate that boratrane-modified resins exhibit a stable BO4- structure, which prevents self-condensation of boratrane to B2O3 and enhances the thermal stability of oxygenated resins. This improvement is due to the formation of intramolecular hydrogen bonds, contributing to helix-like structures that strengthen the resin. The mechanism by which the BO4- structure terminates radical agents and transforms into carbonaceous material is elucidated through thermodynamic values, revealing the plausible reactions and chemical structure of boron in the resulting material.

Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions.

Proteins form native structures through folding processes, many of which proceed through intramolecular hydrophobic effect, hydrogen bond and disulfide-bond formation. In vivo, protein aggregation is prevented even in the highly condensed milieu of a cell through folding mediated by molecular chaperones and oxidative enzymes. Chemical approaches to date have not replicated such exquisite mediation. Oxidoreductases efficiently promote folding by the cooperative effects of oxidative reactivity for disulfide-bond formation in the client unfolded protein and chaperone activity to mitigate aggregation. Conventional synthetic folding promotors mimic the redox-reactivity of thiol/disulfide units but do not address client-recognition units for inhibiting aggregation. Herein, we report thiol/disulfide compounds containing client-recognition units, which act as synthetic oxidoreductase-mimics. For example, compound βCDWSH/SS bears a thiol/disulfide unit at the wide rim of β-cyclodextrin as a client recognition unit. βCDWSH/SS shows promiscuous binding to client proteins, mitigates protein aggregation, and accelerates disulfide-bond formation. In contrast, positioning a thiol/disulfide unit at the narrow rim of β-cyclodextrin promotes folding less effectively through preferential interactions at specific residues, resulting in aggregation. The combination of promiscuous client-binding and redox reactivity is effective for the design of synthetic folding promoters. βCDWSH/SS accelerates oxidative protein folding at highly condensed sub-millimolar protein concentrations.

Characterizing the Dynamics of Solvated Disaccharides with In-Electrospray Ionization Hydrogen/Deuterium Exchange-Mass Spectrometry.

Carbohydrates have various biological functions that are based on their structures. However, the composition and the glycosidic-bond linkage and configuration of carbohydrates present challenges for their characterization. Furthermore, isomeric features contribute to the formation of intramolecular hydrogen bonds, which influence the flexibility and dynamics of carbohydrates. Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) enables the analysis of protein dynamics by monitoring deuterium labeling after HDX for different lengths of time. In-electrospray ionization (in-ESI) HDX-MS has been used to rapidly label solvated carbohydrates with labeling occurring during desolvation of ESI droplets. Therefore, HDX-labeling times can be altered by changing the spray-solvent conductivity, which changes the initial size of ESI droplets and their resulting lifetimes. Here, we utilize in-ESI HDX-MS to characterize nine isomeric disaccharides with different monosaccharide compositions and glycosidic-bond linkages and configurations. We compared both the relative D-uptake of isomers at individual conductivities, or HDX-labeling times, and the trends associated with labeling at multiple conductivities. Interestingly, the relative D-uptake trends were correlated to isomeric features that affect disaccharide flexibility, including formation of intramolecular hydrogen bonds. Among the isomeric features studied, linkage was observed to have a significant influence on relative D-uptake with (1-3)-linked disaccharides having more change in relative D-uptake with changing conductivity compared to other linkages. Overall, this research illustrates how in-ESI HDX-MS can be applied to structurally characterize disaccharides with distinct isomeric features. Furthermore, this work shows that in-ESI HDX-MS can be used to monitor the dynamics of solvated molecules with rapidly exchanging functional groups.

Nitrogen-Embedding Strategy for Short-Range Charge Transfer Excited States and Efficient Narrowband Deep-Blue Organic Light Emitting Diodes.

The development of deep-blue organic light-emitting diodes (OLEDs) featuring high efficiency and narrowband emission is of great importance for ultrahigh-definition displays with wide color gamut. Herein, based on the nitrogen-embedding strategy for modifying the short range charge transfer excited state energies of multi-resonance (MR) thermally activated delayed fluorescence (TADF) emitters, we introduce one or two nitrogen atoms into the central benzene ring of a versatile boron-embedded 1,3-bis(carbazol-9-yl)benzene skeleton. This approach resulted in the stabilization of the highest occupied molecular orbital energy levels and the formation of intramolecular hydrogen bonds, and thus systematic hypsochromic shifts and narrowing spectra. In toluene solution, two heterocyclic-based MR-TADF molecules, Py-BN and Pm-BN, exhibit deep-blue emissions with high photoluminescence quantum yields of 93 % and 94 %, and narrow full width at half maximum of 14 and 13 nm, respectively. A deep-blue hyperfluorescent OLED based on Py-BN exhibited a maximum external quantum efficiency of 27.7 % and desired color purity with Commission Internationale de L'Eclairage (CIE) coordinates of (0.150, 0.052). These results demonstrate the significant potential for the development of deep blue narrowband MR-TADF emitters.

Nitrogen‐Embedding Strategy for Short‐Range Charge Transfer Excited States and Efficient Narrowband Deep‐Blue Organic Light Emitting Diodes

AbstractThe development of deep‐blue organic light‐emitting diodes (OLEDs) featuring high efficiency and narrowband emission is of great importance for ultrahigh‐definition displays with wide color gamut. Herein, based on the nitrogen‐embedding strategy for modifying the short range charge transfer excited state energies of multi‐resonance (MR) thermally activated delayed fluorescence (TADF) emitters, we introduce one or two nitrogen atoms into the central benzene ring of a versatile boron‐embedded 1,3‐bis(carbazol‐9‐yl)benzene skeleton. This approach resulted in the stabilization of the highest occupied molecular orbital energy levels and the formation of intramolecular hydrogen bonds, and thus systematic hypsochromic shifts and narrowing spectra. In toluene solution, two heterocyclic‐based MR‐TADF molecules, Py‐BN and Pm‐BN, exhibit deep‐blue emissions with high photoluminescence quantum yields of 93 % and 94 %, and narrow full width at half maximum of 14 and 13 nm, respectively. A deep‐blue hyperfluorescent OLED based on Py‐BN exhibited a maximum external quantum efficiency of 27.7 % and desired color purity with Commission Internationale de L'Eclairage (CIE) coordinates of (0.150, 0.052). These results demonstrate the significant potential for the development of deep blue narrowband MR‐TADF emitters.

Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y14 Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

Long-wavelength emission room-temperature phosphorescent carbon dots activated by an ortho-carboxyl substitution strategy and employed for achieving tunable LED

While room temperature phosphorescence (RTP) associated with carbon dots (CDs) has been widely achieved, obtaining long-wavelength emission RTP, especially while mitigating the quenching effect of water or dissolved oxygen, remains a challenging yet desirable goal. We synthesized three types of phosphorescent CDs with varying luminescent properties by using three precursors with carboxyls positioned differently. The formation process of these CDs resulted in a well-ordered and compact structure, effectively inhibiting molecular vibrations and reducing non-radiative transitions. Consequently, it successfully prevented the quenching effect of dissolved oxygen on the RTP of CDs in an aqueous environment. Significantly, PA-AIBN synthesized with phthalic acid, rather than iso-phthalic acid and terephthalic acid, exhibited long-wavelength emission RTP, with the phosphorescent emission center reaching as far as 640 nm. To be specific, the ortho-substituted carboxyls played a critical role in boosting the formation of intramolecular hydrogen bonds. Simultaneously, an increase in the doping levels of both nitrogen (N) and phosphorus (P) in PA-AIBN facilitated the long-wavelength emission RTP. The increased sp2 conjugated carbon core of PA-AIBN narrowed the optical band gap, contributing to the long-wavelength emission. Taken together, these factors cooperatively promoted the long-wavelength emission of RTP. Importantly, the PA-AIBN synthesized in this study exhibited a broad half-peak width and long-wavelength emission. It was successfully used in the preparation of white-light-emitting diodes without the need for commercial phosphor powder, demonstrating its enormous potential for practical lighting devices.

Quantitative lithium substitution of carboxyl hydrogens in polyacrylic acid binder enables robust SiO electrodes with durable lithium storage stability

The design of advanced binders plays a critical role in stabilizing the cycling performance of large-volume-effect silicon monoxide (SiO) anodes. For the classic polyacrylic acid (PAA) binder, the self-association of –COOH groups in PAA leads to the formation of intramolecular and intermolecular hydrogen bonds, greatly weakening the bonding force of the binder to SiO surface. However, strengthening the binder-material interaction from the perspective of binder molecular regulation poses a significant challenge. Herein, a modified PAA-Lix (0.25 ≤ x ≤ 1) binder with prominent mechanical properties and adhesion strength is specifically synthesized for SiO anodes by quantitatively substituting the carboxylic hydrogen with lithium. The appropriate lithium substitution (x = 0.25) not only effectively increases the number of hydrogen bonds between the PAA binder and SiO surface owing to charge repulsion effect between ions, but also guarantees moderate entanglement between PAA-Lix molecular chains through the ion–dipole interaction. As such, the PAA-Li0.25/SiO electrode exhibits exceptional mechanical properties and the lowest volume change, as well as the optimum cycling (1237.3 mA h g−1 after 100 cycles at 0.1 C) and rate performance (1000.6 mA h g−1 at 1 C), significantly outperforming the electrode using pristine PAA binder. This work paves the way for quantitative regulation of binders at the molecular level.

Simultaneous adsorption of anionic and cationic species on UiO-66 and MIL-125 MOFs: Mechanisms & selectivity

Metal-organic frameworks (MOFs) have attractive properties, including regular pore structure, high specific surface area, tunable surface properties, and abundant active sites. Such properties have boosted their recent development in many fields, including water treatment. In this study, MOFs composed of tetravalent metals (Ti4+ and Zr4+) and dicarboxylate linker (terephthalate – BDC) were modified using surface functionalization and/or pore structure through defect engineering to enhance adsorption properties. It has been shown that the Ti-containing materials (MIL-125) show a greater affinity for cationic species, while the Zr-containing samples (UiO-66) have a higher affinity for anionic species. Surface charge and electrostatic interactions could account for such a difference in adsorption properties. Zeta potential measurements showed that MIL-125 has a more negative surface charge for both non-functionalized and amino-functionalized versions, which favors the interaction with cationic molecules. On the other hand, UiO-66 has a more positive surface, which facilitates interactions with anionic molecules. Within each MOF family, the non-functionalized structures emerged as the best-performing materials. Specifically, MIL-125(H) and UiO-66(H)_5eq, with 5eq denoting the amount of H2O added during synthesis, showed superior performance. Furthermore, by performing simultaneous adsorption experiments with anionic and cationic contaminants, it was found that the adsorption of the anionic dye acid orange 7 (AO7) onto the UiO-66 framework is primarily based on specific interactions between the sulfonic group (-SO3-) within the AO7 molecule and the inorganic core Zr6O4(OH)4 of UiO-66. The interaction between MIL-125 and the cationic dye methylene blue (MB) was found to be more delocalized, based on electrostatic and π-π interactions between the benzene domains. Finally, except for MIL-125(H), all the tested MOFs showed high stability in water and in the adsorption process. The higher stability of UiO-66 over MIL-125 materials can be attributed to steric effects and lower metal electronegativity. Compared to MIL-125(H), the higher stability of MIL-125(NH2) is probably related to the formation of intramolecular hydrogen bonds.

Insight into the binding characteristics of epigallocatechin-3-O-gallate and alcohol dehydrogenase: Based on the spectroscopic and molecular docking analysis

Alcohol dehydrogenase (ADH) is one of the pivotal enzymes for alcohol metabolism, which plays an important role in many physiological processes. In this study, the activation effects of epigallocatechin-3-O-gallate (EGCG) on ADH and the characteristics of the interaction were investigated via biochemical method, spectroscopy methods, and molecular docking. The results demonstrated that EGCG significantly increased the catalytic activity of ADH with a 33.33% activation rate and that EGCG blending slightly altered the microenvironment surrounding ADH aromatic amino acids, with an increase in the quantity of β-sheet and a decrease in the α-helix. Through the thermal stability analysis, it is further shown that the interaction of the two affects the intra-molecular hydrogen bond formation of the protein, and the conformation is partially extended. Besides, a total of 8 residues in ADH participated in the docking with EGCG, among which Asp-227, Lys-231, Glu-234, Gly-365 and Glu-366 participated in the formation of hydrogen bonds. At the same time, EGCG and amino group of Lys-231 form a noncovalent bond through cation-π interaction. In particular, hydrogen bonding was beneficial to keep the stability of EGCG-ADH, which was the primary driver of ADH activity activation. The results supply a new way for EGCG to activate ADH and a theoretical basis for the development of anti-alcoholism products.

Creating Efficient Red Thermally Activated Delayed Fluorescence Materials with Cyano-Substituted 11,12-Diphenyldipyrido[3,2-a:2',3'-c]phenazine Acceptors.

Red luminescent materials are essential components for full color display and white lightening based on organic light-emitting diode (OLED) technology, but the extension of emission color towards red or deep red region generally leads to decreased photoluminescence and electroluminescence efficiencies. Herein, we wish to report two new luminescent molecules (2CNDPBPPr-TPA and 4CNDPBPPr-TPA) consisting of cyano-substituted 11,12-diphenyldipyrido[3,2-a:2',3'-c]phenazine acceptors and triphenylamine donors. As the increase of cyano substituents, the emission wavelength is greatly red-shifted and the reverse intersystem crossing process is promoted, resulting in strong red delayed fluorescence. Meanwhile, due to the formation of intramolecular hydrogen bonds, the molecular structures become rigidified and planarized, which brings about large horizontal dipole ratios. As a result, 2CNDPBPPr-TPA and 4CNDPBPPr-TPA can perform as emitters efficiently in OLEDs, furnishing excellent external quantum efficiencies of 28.8 % at 616 nm and 20.2 % at 648 nm, which are significantly improved in comparison with that of the control molecule without cyano substituents. The findings in this work demonstrate that the introduction of cyano substituents to the acceptors of delayed fluorescence molecules could be a facile and effective approach to explore high-efficiency red or deep red delayed fluorescence materials.

Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir

AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL.

A synthetic approach towards drug modification: 2-hydroxy-1-naphthaldehyde based imine-zwitterion preparation, single-crystal study, Hirshfeld surface analysis, and computational investigation.

The current work is about the modification of primary amine functionalized drugs, pyrimethamine and 4-amino-N-(2,3-dihydrothiazol-2-yl)benzenesulfonamide, via condensation reaction with 2-hydroxy-1-naphthaldehyde to produce new organic zwitterionic compounds (E)-1-(((4-(N-(2,3-dihydrothiazol-2-yl)sulfamoyl)phenyl)iminio)methyl)naphthalen-2-olate (DSPIN) and (E)-1-(((4-amino-5-(4-chlorophenyl)-6-ethylpyrimidin-2-yl)iminio)methyl)naphthalen-2-olate (ACPIN) in methanol as a solvent. The crystal structures of both compounds were confirmed to be imine-based zwitterionic products via single-crystal X-ray diffraction (SC-XRD) analysis which indicated that the stabilization of both crystalline compounds is achieved via various noncovalent interactions. The supramolecular assembly in terms of noncovalent interactions was explored by the Hirshfeld surface analysis. Void analysis was carried out to predict the crystal mechanical response. Compound geometries calculated in the DFT (Density Functional Theory) study showed reasonably good agreement with the experimentally determined structural parameters. Frontier molecular orbital (FMO) analysis showed that the DSPIN HOMO/LUMO gap is by 0.15 eV smaller than the ACPIN HOMO/LUMO gap due to some destabilization of the DSPIN HOMO and some stabilization of its LUMO. The results of the charge analysis implied formation of intramolecular hydrogen bonds and suggested formation of intermolecular hydrogen bonding and dipole-dipole and dispersion interactions.

Stereo effects for efficient synthesis of orange-red multiple resonance emitters centered on a pyridine ring.

Despite theoretical difficulties, we herein demonstrate an effective strategy for the inaugural synthesis of an orange-red multiple resonance (MR) emitter centered on a pyridine ring via stereo effects. Compared to conventional benzene-centered materials, the pyridine moiety in the novel MR material acts as a co-acceptor. This results in a significant spectral redshift and a narrower spectrum, as well as an improved photoluminescence quantum yield (PLQY) due to the formation of intramolecular hydrogen bonds. As envisioned, the proof-of-concept emitter Py-Cz-BN exhibits bright orange-red emission peaking at 586 nm with a small full width at half maximum (FWHM) of 0.14 eV (40 nm), exceeding both the wavelength and FWHM achieved with benzene-centered BBCz-Y. Benefiting from high PLQYs (>92%) and suppressed chromophore interactions, the optimized organic light-emitting diodes achieved high maximum external quantum efficiencies of 25.3-29.6%, identical small FWHMs of 0.18 eV (54 nm), and long lifetimes over a wide range of dopant concentrations (1-15 wt%). The performance described above demonstrates the effectiveness of this molecular design and synthesis strategy in constructing high performance long-wavelength MR emitters.

Solvent and Substituent Size Influence on the Cyclochiral Rigidity of Aminomethylene Derivatives of Resorcin[4]arene.

Resorcin[4]arenes (R[4]A) are a group of macrocyclic compounds whose peculiar feature is the presence of eight hydroxyl groups in their structure. The directional formation of intramolecular hydrogen bonds with their participation leads to the formation of a cyclochiral racemic mixture of these compounds. Their stability strongly depends on the substituent and especially the environment in which they are located. The paper discusses the cyclochiral nature of aminomethylene derivatives of R[4]A (AMD-R[4]A). Their cyclochiral rigidity in non-polar solvents has been shown. The influence of the size of the alkyl groups in the amino substituents of AMD-R[4]A on their cyclochiral nature was noted. To calculate the reaction paths for their racemization, the nudged elastic band (NEB) method was employed using the semi-empirical DFT (GFN1-xTB) approach. The calculated activation barrier energies for their racemization in chloroform, obtained through various semi-empirical quantum chemical methods (SE), Hartree-Fock (HF), and density functionals theory (DFT), show good correlation with experimental observations. Among the tested methods, the B38LYP-D4 method is highly recommended due to its fast computational speed and accuracy, which is comparable to the time-consuming double-hybrid DH-revDSD-PBEP86 approach.

How to More Effectively Obtain Ginsenoside Rg5: Understanding Pathways of Conversion.

Ginsenoside Rg5, a relatively uncommon secondary ginsenoside, exhibits notable pharmacological activity and is commonly hypothesized to originate from the dehydration of Rg3. In this work, we compared different conversion pathways using Rb1, R-Rg3 and S-Rg3 as the raw material under simple acid catalysis. Interestingly, the results indicate that the conversion follows this reaction activity order Rb1 > S-Rg3 > R-Rg3, which is contrary to the common understanding of Rg5 obtained from Rg3 by dehydration. Our experimental results have been fully confirmed by theoretical calculations and a NOESY analysis. The DFT analysis reveals that the free energies of S-Rg3 and R-Rg3 in generating carbocation are 7.56 mol/L and 7.57 mol/L, respectively, which are significantly higher than the free energy of 1.81 mol/L when Rb1 generates the same carbocation. This finding aligns with experimental evidence suggesting that Rb1 is more prone to generating Rg5 than Rg3. The findings from the nuclear magnetic resonance (NMR) analysis suggest that the fatty chains (C22-C27) in R-Rg3 and S-Rg3 adopt a Gauche conformation and an anti conformation with C16-C17 and C13-C17, respectively, due to the relatively weak repulsive van der Waals force. Therefore, the configuration of R-Rg3 is more conducive to the formation of intramolecular hydrogen bonds between 20C-OH and 12C-OH, whereas S-Rg3 lacks this capability. Consequently, this also explains the fact that S-Rg3 is more prone to dehydration to generate Rg5 than R-Rg3. Additionally, our research reveals that the synthetic route of Rg5 derived from protopanaxadiol (PPD)-type ginsenosides (including Rb1, Rb2, Rb3, Rc and Rd) exhibits notable advantages in terms of efficacy, purity and yield when compared to the pathway originating from Rg3. Moreover, this study presents a highly effective and practical approach for the extensive synthesis of Rg5, thereby facilitating the exploration of its pharmacological properties and potential application in drug discovery.

Dependence of Intramolecular Hydrogen Bond on Conformational Flexibility in Linear Aminoalcohols.

Intramolecular hydrogen bonds (H-bonds) are abundant in physicochemical and biological processes. The strength of such interaction is governed by a subtle balance between conformational flexibility and steric effect that are often hard to predict. Herein, using linear aminoalcohols NH2(CH2)nOH (n = 2-5) as a model system, we demonstrated the dependence of intramolecular H-bond on the backbone chain length. With sensitive photoacoustic Raman spectroscopy (PARS), the gas-phase Raman spectra of aminoalcohols were measured in both N-H and O-H stretching regions at 298 and 338 K and explained with the aid of quantum chemistry calculations. For n = 2-4, two conformers corresponding to the O-H···N intramolecular H-bond and free OH were identified, whereas for n = 5, only the free-OH conformer was identified. Compared to free OH, a striking spectral dependence was observed for the intramolecular H-bonded conformer. According to the red shift of the OH-bonded band, the strongest intramolecular H-bond yields in n = 4, but the favorable chain length to form an intramolecular hydrogen bond at room temperature was observed in n = 3, which corresponds to a six-membered-ring in 3-aminopropanol. This is in good agreement with statistical analysis from the Cambridge Structural Database (CSD) that the intramolecular hydrogen bond is preferred when the six-membered ring is formed. Furthermore, combined with the calculated thermodynamic data at the MP2/aug-cc-pVTZ//M062X/6-311++G(d,p) level, the origin of decrease in intramolecular hydrogen-bond formation was ascribed to an unfavorable negative entropy contribution when the backbone chain is further getting longer, which results in the calculated Gibbs free energy optimum changing with increasing temperature from n = 4 (0-200 K) to n = 3 (200-400 K) and to n = 2 (above 400 K). These results will provide new insight into the nature of intramolecular hydrogen bonds at the molecular level and the application of intramolecular hydrogen bonds in rational drug design and supramolecular assembly.

Installing hydrogen bonds as a general strategy to control viscosity sensitivity of molecular rotor fluorophores

AbstractMolecular rotor‐based fluorophores (RBFs) activate fluorescence upon increase of micro‐viscosity, thus bearing a broad application promise in many fields. However, it remains a challenge to control how fluorescence of RBFs responds to viscosity changes. Herein, we demonstrate that the formation and regulation of intramolecular hydrogen bonds in the excited state of RBFs could modulate their rotational barrier, leading to a rational control of how their fluorescence can be activated by micro‐viscosity. Based on this strategy, a series of RBFs were developed based on 4‐hydroxybenzylidene‐imidazolinone (HBI) that span a wide range of viscosity sensitivity. Combined with the AggTag method that we previously reported, the varying viscosity sensitivity and emission spectra of these probes enabled a dual‐color imaging strategy that detects both protein oligomers and aggregates during the multistep aggregation process of proteins in live cells. In summary, our work indicates that installing intracellular excited state hydrogen bonds to RBFs allows for a rational control of rotational barrier, thus allow for a fine tune of their viscosity sensitivity. Beyond RBFs, we envision similar strategies can be applied to control the fluorogenic behavior of a large group of fluorophores whose emission is dependent on excited state rotational motion, including aggregation‐induced emission fluorophores.