A general chemical principle for creating closure-stabilizing integrin inhibitors.

Integrins are validated drug targets with six approved therapeutics. However, small-molecule inhibitors to three integrins failed in late-stage clinical trials for chronic indications. Such unfavorable outcomes may in part be caused by partial agonism, i.e., the stabilization of the high-affinity, extended-open integrin conformation. Here, we show that the failed, small-molecule inhibitors of integrins αIIbß3 and α4ß1 stabilize the high-affinity conformation. Furthermore, we discovered a simple chemical feature present in multiple αIIbß3 antagonists that stabilizes integrins in their bent-closed conformation. Closing inhibitors contain a polar nitrogen atom that stabilizes, via hydrogen bonds, a water molecule that intervenes between a serine residue and the metal in the metal-ion-dependent adhesion site (MIDAS). Expulsion of this water is a requisite for transition to the open conformation. This change in metal coordination is general to integrins, suggesting broad applicability of the drug-design principle to the integrin family, as validated with a distantly related integrin, α4ß1.

Helical twists and ß-turns in structures at serine-proline sequences: Stabilization of cis-proline and type VI ß-turns via C-H/O interactions.

Structures at serine-proline sites in proteins were analyzed using a combination of peptide synthesis with structural methods and bioinformatics analysis of the PDB. Dipeptides were synthesized with the proline derivative (2S,4S)-(4-iodophenyl)hydroxyproline [hyp(4-I-Ph)]. The crystal structure of Boc-Ser-hyp(4-I-Ph)-OMe had two molecules in the unit cell. One molecule exhibited cis-proline and a type VIa2 ß-turn (BcisD). The cis-proline conformation was stabilized by a C-H/O interaction between Pro C-Hα and the Ser side-chain oxygen. NMR data were consistent with stabilization of cis-proline by a C-H/O interaction in solution. The other crystallographically observed molecule had trans-Pro and both residues in the PPII conformation. Two conformations were observed in the crystal structure of Ac-Ser-hyp(4-I-Ph)-OMe, with Ser adopting PPII in one and the ß conformation in the other, each with Pro in the δ conformation and trans-Pro. Structures at Ser-Pro sequences were further examined via bioinformatics analysis of the PDB and via DFT calculations. Ser-Pro versus Ala-Pro sequences were compared to identify bases for Ser stabilization of local structures. C-H/O interactions between the Ser side-chain Oγ and Pro C-Hα were observed in 45% of structures with Ser-cis-Pro in the PDB, with nearly all Ser-cis-Pro structures adopting a type VI ß-turn. 53% of Ser-trans-Pro sequences exhibited main-chain COi•••HNi+3 or COi•••HNi+4 hydrogen bonds, with Ser as the i residue and Pro as the i + 1 residue. These structures were overwhelmingly either type I ß-turns or N-terminal capping motifs on α-helices or 310-helices. These results indicate that Ser-Pro sequences are particularly potent in favoring these structures. In each, Ser is in either the PPII or ß conformation, with the Ser Oγ capable of engaging in a hydrogen bond with the amide N-H of the i + 2 (type I ß-turn or 310-helix; Ser χ1 t) or i + 3 (α-helix; Ser χ1 g+) residue. Non-proline cis amide bonds can also be stabilized by C-H/O interactions.

Mutual influence of non-covalent interactions formed by imidazole: A systematic quantum-chemical study.

Imidazole is a five-membered heterocycle that is part of a number of biologically important molecules such as the amino acid histidine and the hormone histamine. Imidazole has a unique ability to participate in a variety of non-covalent interactions involving the NH group, the pyridine-like nitrogen atom or the π-system. For many biologically active compounds containing the imidazole moiety, its participation in formation of hydrogen bond NH⋯O/N and following proton transfer is the key step of mechanism of their action. In this work a systematic study of the mutual influence of various paired combinations of non-covalent interactions (e.g., hydrogen bonds and π-interactions) involving the imidazole moiety was performed by means of quantum chemistry (PW6B95-GD3/def2-QZVPD) for a series of model systems constructed based on analysis of available x-ray data. It is shown that for considered complexes formation of additional non-covalent interactions can only enhance the proton-donating ability of imidazole. At the same time, its proton-accepting ability can be both enhanced and weakened, depending on what additional interactions are added to a given system. The mutual influence of non-covalent interactions involving imidazole can be classified as weak geometric and strong energetic cooperativity-a small change in the length of non-covalent interaction formed by imidazole can strongly influence its strength. The latter can be used to develop methods for controlling the rate and selectivity of chemical reactions involving the imidazole fragment in larger systems. It is shown that the strong mutual influence of non-covalent interactions involving imidazole is due to the unique ability of the imidazole ring to effectively redistribute electron density in non-covalently bound systems with its participation.

Biomass and Transparent Supramolecular Elastomers for Green Electronics Enabled by the Controlled Growth and Self-Assembly of Dynamic Polymer Networks.

Determining the optimal method for preparing supramolecular materials remains a profound challenge. This process requires a combination of renewable raw materials to create supramolecular materials with multiple functions and properties, including simple fabrication, sustainability, a dynamic nature, good toughness, and transparency. In this work, a strategy is presented for toughening supramolecular networks based on solid-phase chain extension. This toughening strategy is simple and environmentally friendly. In addition, a series of biobased elastomers are designed and prepared with adjustable performance characteristics. This strategy can significantly improve the transparency, tensile strength, and toughness of the synthesized elastomer. The synthesized biobased elastomers have great ductility, repairability, and recyclability, and they show good adhesion and dielectric properties. A biobased ionic skin is assembled from these biobased elastomers. Assembled ionic skin can sensitively detect external stimuli (such as stretching, bending, compression, or temperature changes) and monitor human movement. The conductive and dielectric layers of the biobased ionic skin are both obtained from renewable raw materials. This research provides novel molecular design approaches and material selection methods for promoting the development of green electronic devices and biobased elastomers.

Stretching Aligned Hydrogen Bonding Network to Evoke Mechanically Robust and High-Energy-Density P(VDF-HFP) Dielectric Film Capacitors.

Polymer-based dielectric film capacitors are essential energy storage components in electronic and power systems due to their ultrahigh power density and ultra-fast charge storage/release capability. Nonetheless, their relatively low energy density does not fully meet the requirements of power electronics and pulsed power systems. Herein, a scalable composite dielectric film based on a ferroelectric polymer with edge hydroxylated boron nitride nanosheets (BNNS-OH) is fabricated via the construction of a hydrogen bonding network and stretching orientation strategy. The presence of hydroxyl groups on boron nitride aids in forming a robust hydrogen bonding network within the ferroelectric polymer, leading to a significant increase in Young's modulus and superior dielectric performance. Furthermore, the stretching process aligns the BNNS-OH and the hydrogen bonding network along the drawing direction via covalent and hydrogen bonding interaction, resulting in a remarkable tensile strength (109 MPa), breakdown strength (688 MV m-1), and energy density (28.2 J cm-3), outperforming mostrepresentative polymer-based dielectric films. In combining the advantages of a simple preparation process, extraordinary energy storage performance, and low-cost raw materials, this strategy is viable for large-scale production of polymer-based dielectric films with high mechanical and dielectric performance and opens a new path for the development of next-generation energy storage applications.

High-Power-Density and Excellent-Flexibility Thermoelectric Generator Based on All-SWCNTs/PVP Composites.

Flexible polymer/single-wall carbon nanotube (SWCNT) composites are a vital component for wearable/portable electronics, but the development of their n-type counterpart is laggard. Furthermore, little attention is paid to the interaction between SWCNT and polymers, especially the unconjugated polymers, as well as the conversion mechanism of conduction characteristics. Here, the n-type flexible SWCNTs/Polyvinyl Pyrrolidone (PVP) films are successfully fabricated, where the oxygen atoms in PVP interacted with SWCNT via hydrogen bonds, which can lower the energy barrier of electron tunneling, providing the pathway for the electron transfer. Furthermore, with the increasing synthesis temperature, the hydrogen bonds strengthened and the thermal activation energy further improved, both of which enhanced the electron-donating ability of PVP, resulting in a high-power-factor value of 260 µW m-1 K-2. Based on the optimized SWCNTs/PVP films, a thermoelectric module is assembled, which achieved a power density of 400 µW cm-2 at a temperature difference of 56 K, coupled with excellent flexibility, showing a less than 1% variation of resistance after 5000 bending cycles. It shows the highest output-performance and the best flexibility among the reported SWCNT-based thermoelectric modules. This work provides significant insights into the interaction mechanism and performance optimization of hybrid thermoelectric composites, based on SWCNTs/unconjugated polymers.

Enhancing Nitrate Reduction to Ammonia Through Crystal Phase Engineering: Unveiling the Hydrogen Bonding Effect in δ-FeOOH Electrocatalysis.

Crystal phase engineering has emerged as a powerful tool for tailoring the electrocatalytic performance, yet its impact on nitrate reduction to ammonia (NRA) remains largely uncharted territory. Herein, density functional theory (DFT) calculations are performed to unravel the influence of the crystal phase of FeOOH on the adsorption behavior of *NO3. Inspiringly, FeOOH samples with four distinct crystal phases (δ, γ, α, and ß) are successfully synthesized and deployed as electrocatalysts for NRA. Remarkably, among all FeOOH samples, δ-FeOOH demonstrates the superior NRA performance, achieving a NH3 Faradic efficiency ( FE NH 3 $\rm{FE} _ {\rm{NH_3}}$ ) of 90.2% at -1.0 V versus reversible hydrogen electrode (RHE) and a NH3 yield rate ( Yield NH 3 $\rm{Yield} _ {\rm{NH_3}}$ ) of 5.73 mg h-1 cm-2 at -1.2 V. In-depth experiments and theoretical calculations unveil the existence of hydrogen bonding interaction between δ-FeOOH and *NOx, which not only enhances the adsorption of *NOx but also disrupts the linear relationships between the free energy of *NO3 adsorption and various parameters, including limiting potential, d-band center (εd) and transferred charge from FeOOH to *NO3, ultimately contributing to the exceptional NRA performance.

Porous Supramolecular Crystalline Probe that Detects Non-Covalent Interactions Involved in Molecular Recognition of Furanic Compounds.

Selective separation and conversion of furan-based biomass-derived compounds, which are closely related to biorefineries, is currently an important issue. To improve their performance, it is important to deepen the understanding of non-covalent interactions that act on the molecular recognition of furanic compounds on separation or catalyst matrices. Here, a new method is reported to comprehensively visualize such intermolecular interactions using a porous supramolecular crystalline probe with polar and non-polar binding sites within a low-symmetric nanochannel consisting of four isomeric PdII 3-macrocycles. Single-crystal X-ray diffraction analysis of the crystals including 5-hydroxymethylfurfural, furfural, furfuryl alcohol, or 2-acetylfuran reveals a variety of interactions involving their furan rings and polar substituents. It is also found that cooperative and competitive effects between guest and solvent molecules significantly change their recognition mode.

Hybrid Hydrogen Bonding Strategy to Construct Instantaneous Self-Healing Highly Elastic Ionohydrogel for Multi-Functional Electronics.

Gels show great promise for applications in wearable electronics, biomedical devices, and energy storage systems due to their exceptional stretchability and adjustable electrical conductivity. However, the challenge lies in integrating multiple functions like elasticity, instantaneous self-healing, and a wide operating temperature range into a single gel. To address this issue, a hybrid hydrogen bonding strategy to construct gel with these desirable properties is proposed. The intricate network of hybrid strong weak hydrogen bonds within the polymer matrix enables these ionohydrogel to exhibit remarkable instantaneous self-healing, stretching up to five times their original length within seconds. Leveraging these properties, the incorporation of ionic liquids, water, and zinc salts into hybrid hydrogen bond crosslinked network enables conductivity and redox reaction, making it a versatile ionic skin for real-time monitoring of human movements and respiratory. Moreover, the ionohydrogel can be used as electrolyte in the assembly of a zinc-ion battery, ensuring a reliable power supply for wearable electronics, even in extreme conditions (-20 °C and extreme deformations). This ionohydrogel electrolyte simplifies the diverse structural requirements of gels to meet the needs of various electronic applications, offering a new approach for multi-functional electronics.

Mechanically Ultra-Robust Fluorescent Elastomer for Elaborating Auxetic Composite.

Fluorescent elastomers are predominantly fabricated through doping fluorescent components or conjugating chromophores into polymer networks, which often involves detrimental effects on mechanical performance and also makes large-scale production difficult. Inspired by the heteroatom-rich microphase separation structures assisted by intensive hydrogen bonds in natural organisms, an ultra-robust fluorescent polyurethane elastomer is reported, which features a remarkable fracture strength of 87.2 MPa with an elongation of 1797%, exceptional toughness of 678.4 MJ m-3 and intrinsic cyan fluorescence at 445 nm. Moreover, the reversible fluorescence variation with temperature could in situ reveal the microphase separation of the elastomer in real time. By taking advantage of mechanical properties, intrinsic fluorescence and hydrogen bonds-promoted interfacial bonding ability, this fluorescent elastomer can be utilized as an auxetic skeleton for the elaboration of an integrated auxetic composite. Compared with the auxetic skeleton alone, the integrated composite shows an improved mechanical performance while maintaining auxetic deformation in a large strain below 185%, and its auxetic process can be visually detected under ultraviolet light by the fluorescence of the auxetic skeleton. The concept of introducing hydrogen-bonded heteroatom-rich microphase separation structures into polymer networks in this work provides a promising approach to developing fluorescent elastomers with exceptional mechanical properties.

Enhanced Intrinsic Self-Healing Performance of Mussel Inspired Coating via In-Situ Cation Capture.

Under damp or aquatic conditions, the corrosion products deposited on micro-cracks/pore sites bring about the failure of intrinsically healable organic coatings. Inspired by mussels, a composite coating of poly (methyl methacrylate-co-butyl acylate-co-dopamine acrylamide)/phenylalanine-functionalized boron nitride (PMBD/BN-Phe) is successfully prepared on the reinforcing steel, which exhibits excellent anti-corrosion and underwater self-healing capabilities. The self-healing property of PMBD is derived from the synergistic effect of hydrogen bonding and metal-ligand coordination bonding, and thereby the continuous generation of corrosion products can be significantly suppressed through in situ capture of cations by the catechol group. Furthermore, the corrosion protection ability can be remarkably improved by the labyrinth effect of BN and the inhibition role of Phe, and the desired interfacial compatibility can be formed by the hydrogen bonds between BN-Phe and PMBD matrix. The corrosion current density (icorr) of PMBD/BN-Phe coating is determined as 7.95 × 10-11 A cm-2. The low-frequency impedance modulus (|Z|f  =  0.0 1 Hz is remained at 3.47 × 109 Ω cm2, indicating an ultra-high self-healing efficiency (≈89.5%). It is anticipated to provide a unique strategy for development of an underwater self-healing coating and robust durability for application in anti-corrosion engineering of marine buildings.

Quantum dipole interactions and transient hydrogen bond orientation order in cells, cellular membranes and myelin sheath: Implications for MRI signal relaxation, anisotropy, and T1 magnetic field dependence.

PURPOSE: Despite significant impact on the study of human brain, MRI lacks a theory of signal formation that integrates quantum interactions involving proton dipoles (a primary MRI signal source) with brain intricate cellular environment. The purpose of the present study is developing such a theory. METHODS: We introduce the Transient Hydrogen Bond (THB) model, where THB-mediated quantum dipole interactions between water and protons of hydrophilic heads of amphipathic biomolecules forming cells, cellular membranes and myelin sheath serve as a major source of MR signal relaxation. RESULTS: The THB theory predicts the existence of a hydrogen-bond-driven structural order of dipole-dipole connections within THBs as a primary factor for the anisotropy observed in MRI signal relaxation. We have also demonstrated that the conventional Lorentzian spectral density function decreases too fast at high frequencies to adequately capture the field dependence of brain MRI signal relaxation. To bridge this gap, we introduced a stretched spectral density function that surpasses the limitations of Lorentzian dispersion. In human brain, our findings reveal that at any time point only about 4% to 7% of water protons are engaged in quantum encounters within THBs. These ultra-short (2 to 3 ns), but frequent quantum spin exchanges lead to gradual recovery of magnetization toward thermodynamic equilibrium, that is, relaxation of MRI signal. CONCLUSION: By incorporating quantum proton interactions involved in brain imaging, the THB approach introduces new insights on the complex relationship between brain tissue cellular structure and MRI measurements, thus offering a promising new tool for better understanding of brain microstructure in health and disease.

Influence of O-H⋠⋠⋠Pt interactions on photoluminescent response in the (Et4N)2{[Pt(bph)(CN)2][phenylene-1,4-diresorcinol]} framework.

Tunable photoluminescence (PL) is one of the hot topics in current materials science, and research performed on the molecular phases is at the forefront of this field. We present the new (Et4N)2[PtII(bph)(CN)2]⋅rez3⋅1/3H2O (Pt2rez3) (bph=biphenyl-2,2'-diyl; rez3=3,3",5,5"-tetrahydroxy-1,1':4',1"-terphenyl, phenylene-1,4-diresorcinol coformer, a linear quaternary hydrogen bond donor) co-crystal salt based on the recently appointed promising [PtII(bph)(CN)2]2- luminophore. Within the extended hydrogen-bonded subnetwork [PtII(bph)(CN)2]2- complexes and rez3 coformer molecules form two types of contacts: the rez3O-H⋅⋅⋅Ncomplex ones in the equatorial plane of the complex and non-typical rez3O-H⋅⋅⋅Pt ones along its axial direction. The combined structural, PL, and DFT approach identified the rez3O-H⋅⋅⋅Pt synthons to be crucial in promoting the noticeable uniform redshift of bph ligand centered (LC) emission compared to the LC emission of the (Et4N)2[PtII(bph)(CN)2]⋅H2O (Pt2) precursor, owing to the direct interference of the phenol group with the PtII-bph orbital system via altering the CT processes within. The high-resolution emission spectra for Pt2 and Pt2rez3 were successfully reproduced at 77 K by using the Franck-Cordon expressions. The possibility to tune PL properties along the plausible continuum of rez3O-H⋅⋅⋅Pt synthons is indicated, considering various scenarios of molecular occupation of the space above and below the complex plane.

Urea-Comprising Single Core Diketopyrrolopyrrole Derivatives: Exploring the Synthesis, Self-Assembly and Charge Transport Properties.

Supramolecular electronics exploits the distinctive features stemming from noncovalent interactions, guiding the self-assembly of molecules to craft materials endowed with customized electronic functionalities. Hydrogen-bonded materials, characterized by their capacity to establish dynamic and stable networks, introduce an extra dimension to the development of supramolecular electronic systems. This study presents a comparative analysis of two remarkably small semiconductors utilizing diketopyrrolopyrrole functionalized with urea units as hydrogen-bonding motifs, strategically positioned at opposing ends of the conjugated core. We show how the subtle distinction in functionalization not only influences morphology and self-assembly dynamics via hydrogen-bonding and π-π stacking formation, but also holds significant consequences for ultimate charge transport properties. Our observations into the interplay of noncovalent interactions provide valuable insights and strategic pathways for the design of novel materials with enhanced electronic characteristics.

Synthesis and Structural Revision of a Natural Tetrasaccharide from Starfish Asterias rollestoni Bell.

Starfish provide important saponins with diverse bioactivities as the secondary metabolites, among which 2-O-glycosylated glycosides are commonly found. Preparation of those 1,2-trans 2-O-glycosylated glycosides usually relies on 2-O-acyl participation requiring the selective installation and cleavage of 2-O-acyl groups. A convergent synthesis using 2-O-glycosylated oligosaccharide donors would be more straightforward but also pose greater challenges. Herein, we report a convergent synthesis of a distinctive tetrasaccharide isolated from starfish Asterias rollestoni Bell. Dual 2-(diphenylphosphinoyl)acetyl (DPPA) groups at O3 and O4 on galactose moiety led to high ß-selectivities (ß/α=12/1 or ß only) in the challenging [2+2] glycosylation, giving the desired tetrasaccharides in >90 % yields from the 2-O-glycosylated disaccharide donors. These synthetic studies have also unambiguously revised the structure of these natural tetrasaccharides. This work would facilitate further studies on new inhibitors of α-glucosidase as hypoglycemic drugs.

Hydrogen-Bonded Complex of the Parent Phosphinidene.

The diatomic molecule PH is very reactive, and it serves as the parent compound for phosphinidenes featuring a monovalent phosphorus atom. Herein, we report the characterization and reactivity of a rare hydrogen-bonded complex of PH. Specifically, the molecular complex between PH and HCl has been generated by photolysis of chlorophosphine (H2PCl) at 254 nm in a solid Ar-matrix at 10 K. The IR spectrum of the complex HP⋅⋅⋅HCl and quantum chemical calculations at the UCCSD(T)-F12a/haTZ level consistently prove that the phosphorus atom acts as a hydrogen bond acceptor with a binding energy (D0) of -0.6 kcal mol-1. In line with the observed absorption at 341 nm for the binary complex, the triplet phosphinidene PH undergoes prototype H-Cl bond insertion by reformation of H2PCl upon photoexcitation at 365 nm. However, this hydrogen-bonded complex is unstable in the presence of N2 and HCl, as both molecules prefers stronger interactions with HCl than PH in the observed complexes HP⋅⋅⋅HCl⋅⋅⋅N2 and HP⋅⋅⋅2HCl.

Bifunctional Ligands: Evaluating the Role of Acidic Protons in the Secondary Coordination Sphere.

To evaluate bifunctional ligand reactivity involving NH acidic sites in the secondary coordination sphere of metal complexes, complexes where the proton has been substituted with a methyl group (NMe) are often investigated. An alternative strategy would involve substitution of the NH group for an O. This contribution considers and compares the merits of these approaches; the synthesis and characterization of cationic square planar Rh carbonyl complexes bearing diprotic bispyrazole pyridine ligand L1, and the bis-methylated pyrazole pyridine ligand L1Me are described. The syntheses and characterization of the novel monoprotic pyrazole isoxazole pyridine ligand L2 and aprotic bisisoxazole pyridine ligand L3, and their corresponding Rh carbonyl complexes are also described. The different CO stretching frequencies of all four Rh-complexes suggest that substitutions of NH with NMe, as well as O, lead to significant electronic differences, and these differences are further demonstrated to lead to different ligand addition/substitution reactivities of the four isoelectronic Rh-complexes. Overall, the results suggest that the electronic differences arising due to NH substitutions can be significant and must be accounted for prior to invoking the participation of the proton.

Influence of Polymer Side Chain Size and Backbone Length on the Self-Assembly of Supramolecular Polymer Bottlebrushes.

Hydrogen bonds are a versatile tool for creating fibrous, bottlebrush-like assemblies of polymeric building blocks. However, a delicate balance of forces exists between the steric repulsion of the polymer chains and these directed supramolecular forces. In this work we have systematically investigated the influence of structural parameters of the attached polymers on the assembly behaviour of benzene trisurea (BTU) and benzene tris(phenylalanine) (BTP) conjugates in water. Polymers with increasing main chain lengths and different side chain sizes were prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization of hydroxyethyl acrylate (HEA), tri(ethylene glycol) methyl ether acrylate (TEGA) and oligo(ethylene glycol) methyl ether acrylate (OEGA). The resulting structures were analyzed using small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). Both BTU and BTP formed fibres with PHEA attached, but a transition to spherical morphologies was observed at degrees of polymerisation (DP) of 70 and above. Overall, the main chain length appeared to be a dominating factor in inducing morphology transitions. Increasing the side chain size generally had a similar effect but mainly impeded any aggregation as is the case of POEGA. Interestingly, BTP conjugates still formed fibres, suggesting that the stronger intermolecular interactions can compensate partially for the steric repulsion.

Online-Monitoring of the Enantiomeric Ratio in Microfluidic Chip Reactors Using Chiral Selector Ion Vibrational Spectroscopy.

A novel experimental approach for the rapid online monitoring of the enantiomeric ratio of chiral analytes in solution is presented. The charged analyte is transferred to the gas phase by electrospray. Diastereomeric complexes are formed with a volatile chiral selector in a buffer-gas-filled ion guide held at room temperature, mass-selected, and subsequently spectrally differentiated by cryogenic ion trap vibrational spectroscopy. Based on the spectra of the pure complexes in a small diastereomer-specific spectral range, the composition of diastereomeric mixtures is characterized using the cosine similarity score, from which the enantiomeric ratio in the solution is determined. The method is demonstrated for acidified alanine solutions and using three different chiral selectors (2-butanol, 1-phenylethanol, 1-amino-2-propanol). Among these, 2-butanol is the best choice as a selector for protonated alanine, also because the formation ratio of the corresponding diastereomeric complexes is found to be independent of the nature of the enantiomer. Subsequently, a microfluidic chip is implemented to mix enantiomerically pure alanine solutions continuously and determine the enantiomeric ratio online with minimal sample consumption within one minute and with competitive accuracy.

Rotational Spectroscopy and Conformational Flexibility of 2-Phenylethanethiol: The Dominant S-H⋠⋠⋠π Intramolecular Hydrogen Bond.

We present a rotational-computational investigation of the aromatic mercaptan 2-phenylethanethiol, addressing its potential energy surface, conformational equilibrium, internal dynamics and intramolecular interactions. The experiment used broadband chirped-pulse Fourier transform microwave spectroscopy in a supersonic jet expansion, recording the rotational spectrum in the 2-8 GHz frequency region. Two different conformers were detected in the spectrum. The most intense transitions correspond to a skew (gauche-gauche) conformation, identified as the global minimum. The spectra of ten different isotopologues were assigned for this species, leading to accurate effective and substitution structures. The weaker spectrum presents small tunnelling doublings caused by the torsional motion of the thiol group, which are only compatible with an antiperiplanar skeleton and a gauche thiol. The larger stability of the global minimum is attributed to an intramolecular S-H⋅⋅⋅π weak hydrogen bond. A comparison of the intramolecular interactions in the title molecule and 2-phenylethanol, similarly stabilized by a O-H⋅⋅⋅π hydrogen bond, shows the different strength of these interactions. Density functional (B3LYP-D3, B2PLYP-D3) and ab initio (MP2) calculations were conducted for the molecule.