Short Hydrogen Bond Research Articles

Combination of “Buttressing” and “Clothespin” Effects for Reaching the Shortest NHN Hydrogen Bond in Proton Sponge Cations

A series of previously unknown 2,4,5-tri- and 2,4,5,7-tetrasubstituted 1,8-bis(dimethylamino)naphthalenes and their salts with HBF4 containing bulky spherically shaped substituents (Me, Br, and SiMe3) in the naphthalene ring has been synthesized. Using XRD analysis of 11 samples, the influence of the so-called "buttressing" and "clothespin" effects on their molecular structure and the NHN hydrogen bond geometry in the solid cations were investigated. The combined action of both effects has been shown to significantly increase the compression of the hydrogen bond. As a result, the previous record of the hydrogen bond shortness (N···N = 2.524 Å) has been surpassed in favor of 2.502 Å found for the tetrafluoroborate of 2,4,5,7-tetramethyl-1,8-bis(dimethylamino)naphthalene. The molecular structure of the latter differs by perfect symmetry and practically barrier-free proton transfer in the [NHN]+ bond. On the basis of the results of quantum-chemical calculations, it is suggested that the value of 2.502 Å likely represents or lies very close to the theoretical limit for the short hydrogen bonds between the amine-type nitrogen atoms.

Short Strong Hydrogen Bonds can Hinder Complex Formation: A Stability and Structure Study of Copper(II) Alkyl-N-iminodiacetic Acid Complexes in Aqueous Systems and Solid State

In the present study the solution and coordination chemistry of copper(II)–alkyl-N-iminodiacetate systems are studied in aqueous solution by potentiometry, using ion selective copper and pH electrodes, EXAFS (extended X-ray absorption fine structure) and dye probe molecular absorption spectrophotometry. Alkyl-N-iminodiacetates with varying alkyl chain length, methyl (CH3–), n-hexyl (C6H13–), n-dodecyl (C12H25–) and n-octadecyl (C18H37–) were used to tune the amphiphilic properties of the ligands. The polar head groups have both oxygen (hard Lewis base) and nitrogen donor (border-line Lewis base) atoms. This means that metal ions with different bonding characteristics may bind these ligands differently. Furthermore, the chelating properties of the polar head group may be regulated by pH as the acid–base properties of the imine and carboxylic acid groups are different. Copper(II) forms two stable complexes with alkyl-N-iminodiacetates with short alkyl chains, present as monomers in aqueous solution, log10β1 = 11.10(2), log10β2 = 19.5(2) for methyl-N-iminodiacetate, and log10β1 = 12.22(4), log10β2 = 21.9(2) for n-hexyl-N-iminodiacetate. n-Octadecyl-N-iminodiacetic acid, present as large aggregates in acidic aqueous solution, has short strong hydrogen bonds between carboxylic acid and carboxylate groups in the surface of the aggregates, which hinder complex formation at pH values below 4, obstructs it in the pH region 4–7, while the complex formation behaves as for short-chained alkyl-N-iminodiacetates at pH > 7. The structure around copper in copper(II)–alkyl-N-iminodiacetate complexes in aqueous solution and solid state formed at different pH values and copper(II):alkyl-N-iminodiacetate ratios has been determined by EXAFS. The coordination chemistry of copper(II) shows four strong bonds in the equatorial plane, and two different Cu–O/N bond distances, ca. 0.2 Å apart, in the axial positions of a non-centrosymmetric tetragonally elongated octahedron.

The nature of short hydrogen bonds

Chemical Physics Hydrogen bonding (H-bonding) unquestionably plays an important role in chemical and biological systems and is responsible for some of their unusual properties. Strong, short H-bonds constitute a separate class that, owing to their elusive characterization, has remained a point of contention over the past several decades. Using femtosecond two-dimensional infrared spectroscopy in conjunction with quantum chemical calculations, Dereka et al. demonstrate a powerful way to investigate the nature of short H-bonding (see the Perspective by Bonn and Hunger). Their quantitative characterization of multiple coupled motions in the model system of bifluoride anion [F-H-F]− in aqueous solution reveals several distinctive features of a crossover from conventional to short, strong H-bonding. Science , this issue p. [160][1] see also p. [123][2] [1]: /lookup/doi/10.1126/science.abe1951 [2]: /lookup/doi/10.1126/science.abf3543

Switching between Ultrafast Pathways Enables a Green-Red Emission Ratiometric Fluorescent-Protein-Based Ca2+ Biosensor.

Ratiometric indicators with long emission wavelengths are highly preferred in modern bioimaging and life sciences. Herein, we elucidated the working mechanism of a standalone red fluorescent protein (FP)-based Ca2+ biosensor, REX-GECO1, using a series of spectroscopic and computational methods. Upon 480 nm photoexcitation, the Ca2+-free biosensor chromophore becomes trapped in an excited dark state. Binding with Ca2+ switches the route to ultrafast excited-state proton transfer through a short hydrogen bond to an adjacent Glu80 residue, which is key for the biosensor’s functionality. Inspired by the 2D-fluorescence map, REX-GECO1 for Ca2+ imaging in the ionomycin-treated human HeLa cells was achieved for the first time with a red/green emission ratio change (ΔR/R0) of ~300%, outperforming many FRET- and single FP-based indicators. These spectroscopy-driven discoveries enable targeted design for the next-generation biosensors with larger dynamic range and longer emission wavelengths.

A quantum crystallographic approach to short hydrogen bonds.

In this work we use high-resolution synchrotron X-ray diffraction for electron density mapping, in conjunction with ab initio modelling, to study short O—H⋯O and O+—H⋯O− hydrogen bonds whose behaviour is known to be tuneable by temperature. The short hydrogen bonds have donor–acceptor distances in the region of 2.45 Å and are formed in substituted urea and organic acid molecular complexes of N,N′-dimethylurea oxalic acid 2 : 1 (1), N,N-dimethylurea 2,4-dinitrobenzoate 1 : 1 (2) and N,N-dimethylurea 3,5-dinitrobenzoic acid 2 : 2 (3). From the combined analyses, these complexes are found to fall within the salt-cocrystal continuum and exhibit short hydrogen bonds that can be characterised as both strong and electrostatic (1, 3) or very strong with a significant covalent contribution (2). An additional charge assisted component is found to be important in distinguishing the relatively uncommon O—H⋯O pseudo-covalent interaction from a typical strong hydrogen bond. The electron density is found to be sensitive to the extent of static proton transfer, presenting it as a useful parameter in the study of the salt–cocrystal continuum. From complementary calculated hydrogen atom potentials, we attribute changes in proton position to the molecular environment. Calculated potentials also show zero barrier to proton migration, forming an ‘energy slide’ between the donor and acceptor atoms. The better fundamental understanding of the short hydrogen bond in the ‘zone of fluctuation’ presented in a salt-cocrystal continuum, enabled by studies like this, provide greater insight into their related properties and can have implications in the regulation of pharmaceutical materials.

Interplay between spin crossover and proton migration along short strong hydrogen bonds.

The iron(ii) salt [Fe(bpp)2](isonicNO)2·HisonicNO·5H2O (1) (bpp = 2,6-bis(pyrazol-3-yl)pyridine; isonicNO = isonicotinate N-oxide anion) undergoes a partial spin crossover (SCO) with symmetry breaking at T1 = 167 K to a mixed-spin phase (50% high-spin (HS), 50% low-spin (LS)) that is metastable below T2 = 116 K. Annealing the compound at lower temperatures results in a 100% LS phase that differs from the initial HS phase in the formation of a hydrogen bond (HB) between two water molecules (O4W and O5W) of crystallisation. Neutron crystallography experiments have also evidenced a proton displacement inside a short strong hydrogen bond (SSHB) between two isonicNO anions. Both phenomena can also be detected in the mixed-spin phase. 1 undergoes a light-induced excited-state spin trapping (LIESST) of the 100% HS phase, with breaking of the O4W⋯O5W HB and the onset of proton static disorder in the SSHB, indicating the presence of a light-induced activation energy barrier for proton motion. This excited state shows a stepped relaxation at T1(LIESST) = 68 K and T2(LIESST) = 76 K. Photocrystallography measurements after the first relaxation step reveal a single Fe site with an intermediate geometry, resulting from the random distribution of the HS and LS sites throughout the lattice.

Simple acyclic molecules containing a single charge-assisted O-H group can recognize anions in acetonitrile : water mixtures.

Hydroxypyridinium and hydroxyquinolinium compounds containing acidic O-H groups attached to a cationic aromatic scaffold were synthesized, i.e. N-methyl-3-hydroxypyridinium (1+) and N-methyl-8-hydroxyquinolinium (2+). These very simple compounds are capable of binding to chloride very strongly in CD3CN and with moderate strength in 9 : 1 CD3CN : D2O. Comparison with known association constants reveals that 1+ and 2+ bind chloride in CD3CN or CD3CN : D2O with comparable affinities to receptors containing significantly more hydrogen bond donors and/or higher positive charges. Crystal structures of both compounds with coordinating anions were obtained, and feature short O-Hanion hydrogen bonds. A receptor containing two hydroxyquinolinium groups was also prepared. While the low solubility of this compound caused difficulties, we were able to demonstrate chloride binding in a competitive 1 : 1 CD3CN : CD3OD solvent mixture. Addition of sulfate to this compound results in the formation of a crystallographically-characterised solid state anion coordination polymer.

Enhancing the activity and thermal stability of a phthalate-degrading hydrolase by random mutagenesis

Our previous work has reported that EstJ6 was a phthalate-degrading hydrolase. In the study, a random mutant library was constructed by two rounds of error-prone PCR, three mutants (ET1.1, ET2.1, and ET2.2) with enhanced hydrolytic activity against dibutyl phthalate (DBP) were obtained. The best mutant ET2.2, accumulated three amino acid substitutions (Thr91Met, Ala67Val, and Val249Ile) and exhibited 2.8-fold increase enzyme activity and 2.3-fold higher expression level. Meanwhile, compared with EstJ6, ET2.2 showed over 50% improvement in thermostability (at 50 °C for 1 h) and 1.2-fold increase in 50% methanol tolerance. Kinetic parameters analysis revealed that the Km value for ET2.2 decreased by 60% and the kcat/Km value increased by 166%. The molecular docking indicated that the shortening of hydrogen bond between Ser146-OH and DBP-CO, which may led to an increase in enzyme activity and catalytic efficiency, the enhancement of hydrophobicity of hydrophobic pocket was related to the improvement of organic solvents tolerance, and three hydrophobic amino acid substitutions Thr91Met, Ala67Val, and Val249Ile facilitated to improve the thermal stability and organic solvents tolerance. These results confirmed that random mutagenesis was an effective tool for improving enzyme properties and lay a foundation for practical applications of phthalate-degrading hydrolase in biotechnology and industrial fields.

Tetrel and Pnictogen Bonds Complement Hydrogen and Halogen Bonds in Framing the Interactional Landscape of Barbituric Acids

Experimental and theoretical studies of fluoro-, chloro-, and bromo-substituted derivatives of barbituric acid and indandione show that imide protons form short hydrogen bonds and bromine or, to a lesser extent, chlorine atoms form halogen bonds. The imide nitrogen atoms act as effective pnictogen bond donors, while C(sp2) and C(sp3) atoms act as tetrel bond donors; the resulting N···O and C···O close interactions are a distinctive feature of crystal lattices in all compounds. Importantly, halogen atoms promote the electrophilicity of C(sp3) sites and favor the formation of C(sp3)···O close contacts. Oxygen atoms of carbonyl groups of barbituric and indandione units or of water molecules function as the interaction acceptor sites: namely, they donate electron density to hydrogen, halogen, nitrogen, and carbon atoms. Modeling of various barbituric acid derivatives indicates that the positive electrostatic potentials of π-holes orthogonal to the C(sp2) carbons and σ-holes on the elongation of quasi-axial F/Cl/Br–C(sp3) bonds merge to produce a single well-defined point of the most positive electrostatic potential on one face of the barbituric acids. This single local maximum of the potential on the molecular face is close to the site occupied by the oxygen forming the C(sp3)···O, and C(sp2)···O, short contacts observed in crystals.

Supramolecular Paradigm for Capture and Co‐Precipitation of Gold(III) Coordination Complexes

A new supramolecular paradigm is presented for reliable capture and co-precipitation of haloauric acids (HAuX4 ) from organic solvents or water. Two classes of acyclic organic compounds act as complementary receptors (tectons) by forming two sets of directional non-covalent interactions, (a) hydrogen bonding between amide (or amidinium) NH residues and the electronegative X ligands on the AuX4 - , and (b) electrostatic stacking of the electron deficient Au center against the face of an aromatic surface. X-ray diffraction analysis of four co-crystal structures reveals the additional common feature of proton bridged carbonyls as a new and predictable supramolecular design element that creates one-dimensional polymers linked by very short hydrogen bonds (CO⋅⋅⋅OC distance <2.5 Å). Two other co-crystal structures show that the amidinium-π⋅⋅⋅XAu interaction will reliably engage AuX4 - with high directionality. These acyclic compounds are very attractive as co-precipitation agents within new "green" gold recovery processes. They also have high potential as tectons for controlled self-assembly or co-crystal engineering of haloaurate composites. More generally, the supramolecular paradigm will facilitate the design of next-generation receptors or tectons with high affinity for precious metal square planar coordination complexes for use in advanced materials, nanotechnology, or medicine.

Unusual Spectroscopic and Electric Field Sensitivity of Chromophores with Short Hydrogen Bonds: GFP and PYP as Model Systems.

Short hydrogen bonds, with heavy-atom distances less than 2.7 Å, are believed to exhibit proton delocalization, and their possible role in catalysis has been widely debated. While spectroscopic and/or structural methods are usually employed to study the degree of proton delocalization, ambiguities still arise, and no direct information on the corresponding potential energy surface is obtained. Here, we apply an external electric field to perturb the short hydrogen bond(s) within a collection of green fluorescent protein S65T/H148D variants and photoactive yellow protein mutants, where the chromophore participates in the short hydrogen bond(s) and serves as an optical probe of the proton position. As the proton is charged, its position may shift in response to the external electric field, and the chromophore's electronic absorption can thus reflect the ease of proton transfer. The results suggest that low-barrier hydrogen bonds (LBHBs) are not present within these proteins even when proton affinities between donor and acceptor are closely matched. Exploiting the chromophores as precalibrated electrostatic probes, the covalency of short hydrogen bonds as a nonelectrostatic component is also revealed. A theoretical framework is developed to address a possible contribution of unusually large polarizabilities of short hydrogen bonds due to proton delocalization, but no clear evidence for this phenomenon is found in accordance with the absence of LBHBs.

IR Study on Cellulose with the Varied Moisture Contents: Insight into the Supramolecular Structure.

The following article is the first attempt to investigate the supramolecular structure of cellulose with the varied moisture content by the means of Fourier-transform and near infrared spectroscopy techniques. Moreover, authors aimed at the detailed and precise presentation of IR spectra interpretation approach in order to create a reliable guideline for other researchers. On the basis of obtained data, factors indicating biopolymer crystallinity and development of hydrogen interactions were calculated and the peaks representing hydrogen bonding (7500–6000 cm−1, 3700–3000 cm−1, and 1750–1550 cm−1) were resolved using the Gaussian distribution function. Then, the deconvoluted signals have been assigned to the specific interactions occurring at the supramolecular level and the hydrogen bond length, as well bonding-energy were established. Furthermore, not only was the water molecules adsorption observed, but also the possibility of the 3OH⋯O5 intramolecular hydrogen bond shortening in the wet state was found-from (27,786 ± 2) 10−5 nm to (27,770 ± 5) 10−5 nm. Additionally, it was proposed that some deconvoluted signals from the region of 3000–2750 cm−1 might be assigned to the hydroxyl group-incorporated hydrogen bonding, which is, undoubtedly, a scientific novelty as the peak was not resolved before.

The KDEL trafficking receptor exploits pH to tune the strength of an unusual short hydrogen bond

The endoplasmic reticulum (ER) is the main site of protein synthesis in eukaryotic cells and requires a high concentration of luminal chaperones to function. During protein synthesis, ER luminal chaperones are swept along the secretory pathway and must be retrieved to maintain cell viability. ER protein retrieval is achieved by the KDEL receptor, which recognises a C-terminal Lys-Asp-Glu-Leu (KDEL) sequence. Recognition of ER proteins by the KDEL receptor is pH dependent, with binding occurring under acidic conditions in the Golgi and release under conditions of higher pH in the ER. Recent crystal structures of the KDEL receptor in the apo and peptide bound state suggested that peptide binding drives the formation of a short-hydrogen bond that locks the KDEL sequence in the receptor and activates the receptor for COPI binding in the cytoplasm. Using quantum mechanical calculations we demonstrate that the strength of this short hydrogen bond is reinforced following protonation of a nearby histidine, providing a conceptual link between receptor protonation and KDEL peptide binding. Protonation also controls the water networks adjacent to the peptide binding site, leading to a conformational change that ultimately allows the receptor-complex to be recognized by the COPI system.

Crystal structures of four isomeric hydrogen-bonded co-crystals of 6-methyl-quinoline with 2-chloro-4-nitro-benzoic acid, 2-chloro-5-nitro-benzoic acid, 3-chloro-2-nitro-benzoic acid and 4-chloro-2-nitro-benzoic acid.

The structures of the four isomeric compounds of 6-methyl-quinoline with chloro- and nitro-substituted benzoic acids, C7H4ClNO4·C10H9N, namely, 2-chloro-4-nitro-benzoic acid-6-methyl-quinoline (1/1), (I), 2-chloro-5-nitro-benzoic acid-6-methyl-quinoline (1/1), (II), 3-chloro-2-nitro-benzoic acid-6-methyl-quinoline (1/1), (III), and 4-chloro-2-nitro-benzoic acid-6-methyl-quinoline (1/1), (IV), have been determined at 185-190 K. In each compound, the acid and base mol-ecules are linked by a short hydrogen bond between a carboxyl O atom and an N atom of the base. The O⋯N distances are 2.5452 (12), 2.6569 (13), 2.5640 (17) and 2.514 (2) Å, respectively, for compounds (I)-(IV). In the hydrogen-bonded acid-base units of (I), (III) and (IV), the H atoms are each disordered over two positions with O site:N site occupancies of 0.65 (3):0.35 (3), 0.59 (4):0.41 (4) and 0.48 (5):0.52 (5), respectively, for (I), (III) and (IV). The H atom in the hydrogen-bonded unit of (II) is located at the O-atom site. In all of the crystals of (I)-(IV), π-π inter-actions between the quinoline ring system and the benzene ring of the acid mol-ecule are observed. In addition, a π-π inter-action between the benzene rings of adjacent acid mol-ecules and a C-H⋯O hydrogen bond are observed in the crystal of (I), and C-H⋯O hydrogen bonds and O⋯Cl contacts occur in the crystals of (III) and (IV). These inter-molecular inter-actions connect the acid and base mol-ecules, forming a layer structure parallel to the bc plane in (I), a column along the a-axis direction in (II), a layer parallel to the ab plane in (III) and a three-dimensional network in (IV). Hirshfeld surfaces for the title compounds mapped over d norm and shape index were generated to visualize the weak inter-molecular inter-actions.

Polyol and sugar osmolytes can shorten protein hydrogen bonds to modulate function

Polyol and sugar osmolytes are commonly used in therapeutic protein formulations. How they may affect protein structure and function is an important question. In this work, through NMR measurements, we show that glycerol and sorbitol (polyols), as well as glucose (sugar), can shorten protein backbone hydrogen bonds. The hydrogen bond shortening is also captured by molecular dynamics simulations, which suggest a hydrogen bond competition mechanism. Specifically, osmolytes weaken hydrogen bonds between the protein and solvent to strengthen those within the protein. Although the hydrogen bond change is small, with the average experimental cross hydrogen bond 3hJNC′ coupling of two proteins GB3 and TTHA increased by ~ 0.01 Hz by the three osmolytes (160 g/L), its effect on protein function should not be overlooked. This is exemplified by the PDZ3−peptide binding where several intermolecular hydrogen bonds are formed and osmolytes shift the equilibrium towards the bound state.

Quantum effects and 1H NMR chemical shifts of a bifurcated short hydrogen bond.

The monoprotonated compound N,N',N''-tris(p-tolyl)azacalix[3](2,6)pyridine (TAPH) contains an intramolecular hydrogen bond that is formed from three N atoms in its cavity. Constrained by the macrocyclic molecular structure, the separations between the N atoms in this bifurcated hydrogen bond are about 2.6 Å, considerably shorter than those typically observed for hydrogen bonded systems in the condensed phases. As such, TAPH exhibits significantly elongated N-H lengths in its hydrogen bond and a downfield 1H NMR chemical shift of 22.1 ppm. In this work, we carry out ab initio molecular dynamics and ab initio path integral molecular dynamics simulations of TAPH in the acetonitrile solution to reveal the geometry and proton sharing conditions of the bifurcated short hydrogen bond and uncover how the interplay of electronic and nuclear quantum effects gives rise to its far downfield 1H chemical shift. Taking a linear short hydrogen bond as a reference, we demonstrate the distinct features of competing quantum effects and electronic shielding effects in the bifurcated hydrogen bond of TAPH. We further use the degree of deshielding on the proton as a measure of the hydrogen bonding interactions and evaluate the strength of the bifurcated short hydrogen bond as compared to its linear counterpart.

Computational insight of dexamethasone against potential targets of SARS-CoV-2

The health sector has been on the race to find a potent therapy for coronavirus disease (COVID)-19, a diseases caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. Repurposed anti-viral drugs have played a huge role in combating the virus, and most recently, dexamethasone (Dex) have shown its therapeutic activity in severe cases of COVID-19 patients. The study sought to provide insights on the anti-COVID-19 mechanism of Dex at both atomic and molecular level against SARS-CoV-2 targets. Computational methods were employed to predict the binding affinity of Dex to SARS-CoV-2 using the Schrodinger suite (v2020-2). The target molecules and ligand (Dex) were retrieved from PDB and PubChem, respectively. The selected targets were SARS-CoV-2 main protease (Mpro), and host secreted molecules glucocorticoid receptor, and Interleukin-6 (IL-6). Critical analyses such as Protein and ligand preparation, molecular docking, molecular dynamic (MD) simulations, and absorption, distribution, metabolism, excretion (ADME), and toxicity analyses were performed using the targets and the ligand as inputs. Dex showed stronger affinity to its theoretical (glucocorticoid) receptor with a superior docking score of −14.7 and a good binding energy value of −147.48 kcal/mol; while short hydrogen bond distances were observed in both Mpro and IL-6 when compared to glucocorticoid receptor. Based on these findings, Dex-target complexes were used to perform MD simulations to analyze Dex stability at 50 ns. This study demonstrates that Dex could bind to both the viral and host receptors as a potential drug candidate for COVID-19. To ascertain the biological fitness of this study, other SARS-CoV-2 targets should be explored. Also, the in vitro studies of dexamethasone against several SARS-CoV-2 targets warrant further investigation. Communicated by Ramaswamy H. Sarma

On the Case of the Misplaced Hydrogens.

Few other elements play a more central role in biology than hydrogen. The interactions, bonding and movement of hydrogen atoms are central to biological catalysis, structure and function. Yet owing to the elusive nature of a single hydrogen atom few experimental and computational techniques can precisely determine its location. This is exemplified in short hydrogen bonds (SHBs) where the location of the hydrogen atom is indicative of the underlying strength of the bonds, which can vary from 1-5 kcal/mol in canonical hydrogen bonds, to an almost covalent nature in single-well hydrogen bonds. Owing to the often-times inferred position of hydrogen, the role of SHBs in biology has remained highly contested and debated. This has also led to discrepancies in computational, biochemical and structural studies of proteins thought to use SHBs in performing chemistry and stabilizing interactions. Herein, we discuss in detail two distinct examples, namely the conserved catalytic triad and the photoreceptor, photoactive yellow protein, where studies of these SHB-containing systems have permitted contextualization of the role these unique hydrogen bonds play in biology.

Natural-like products as potential SARS-CoV-2 Mpro inhibitors: in-silico drug discovery

In December 2019, a COVID-19 epidemic was discovered in Wuhan, China, and since has disseminated around the world impacting human health for millions. Herein, in-silico drug discovery approaches have been utilized to identify potential natural products (NPs) as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) inhibitors. The MolPort database that contains over 100,000 NPs was screened and filtered using molecular docking techniques. Based on calculated docking scores, the top 5,000 NPs/natural-like products (NLPs) were selected and subjected to molecular dynamics (MD) simulations followed by molecular mechanics–generalized Born surface area (MM-GBSA) binding energy calculations. Combined 50 ns MD simulations and MM-GBSA calculations revealed nine potent NLPs with binding affinities (ΔGbinding ) > −48.0 kcal/mol. Interestingly, among the identified NLPs, four bis([1,3]dioxolo)pyran-5-carboxamide derivatives showed ΔGbinding > −56.0 kcal/mol, forming essential short hydrogen bonds with HIS163 and GLY143 amino acids via dioxolane oxygen atoms. Structural and energetic analyses over 50 ns MD simulation demonstrated NLP-Mpro complex stability. Drug-likeness predictions revealed the prospects of the identified NLPs as potential drug candidates. The findings are expected to provide a novel contribution to the field of COVID-19 drug discovery. Communicated by Ramaswamy H. Sarma

First-principles identification of ferroelectric metal-organic frameworks of [CH3NH3][B(HCOO)3] (B = Mg, Ca, Sr, and Cd)

The ferroelectric instabilities of perovskite-type metal-organic frameworks (MOFs) of [CH3NH3][B(HCOO)3] (B = Mg, Ca, Sr, and Cd) were examined theoretically. Out of these four compounds, the highest ferroelectric instability was observed in [CH3NH3][Sr(HCOO)3]. Energy comparisons of the non-polar Pnma and polar Pna21 space groups confirmed that the polar space group is more stable than the non-polar space group in each compound, and the largest energy difference between these two space groups was found in the Sr-based compound. To determine why the Sr-based system shows the highest amplitude of a ferroelectric mode, the bond distance, including hydrogen bonds, was analyzed systematically. The shortest hydrogen bonds were found in [CH3NH3][Sr(HCOO)3].