Hydrogen Bond Distances Research Articles

Structural characterization of green fluorescent protein in the I-state

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

Regulating the structure and gelling properties of maize starch by non-thermal effect of low intensity radio frequency wave

To verify whether there is a non-thermal effect in the radio frequency (RF) treatment process, it's very important for effectively excluding the thermal effect. Native maize starch (MS) slurry was treated under a specific electric field intensity while maintaining the sample temperature at 25 ± 2 °C for different times (1, 2, 4 and 8 h), which would effectively eliminate the influence of thermal effect on starch. A corresponding low electric field intensity of 3.3–3.4 kV/m was established after adjusting the electrode gap to be 220 mm of the 27.12 MHz RF system. Samples treated without RF-wave for the same time (1, 2, 4 and 8 h) were used as controls. The differences between the effect of these two treatments on the multi-scale structural and gelling properties of starch samples were investigated. Results showed that the low intensity RF-wave treatment enhanced the short-range structural order. A higher degree of order value and the double helical structure were observed from Fourier transform infrared (FTIR) spectra and solid state 13C nuclear magnetic resonance (13C NMR). Moreover, compared to control MS, the crystallinity of low intensity RF-treated starch significantly increased though the crystal pattern remained unchanged. Low intensity RF-wave treated starch had no significant difference in loss modulus, energy and distance of inter-double helices hydrogen bond, and pasting properties (i.e. TV, SB and BD) when compared with control sample. The effect of low intensity RF wave on starch without heating was insufficient to cause macroscopic property changes. These results provide valuable insights into the structural changes of starch treated by low intensity RF-wave and verify that the non-thermal effect of RF waves may be primarily achieved through the dipole polarization mechanism.

Green synthesis of potent anticancer and antibacterial xanthene and chromene derivatives using agar as a catalyst: Molecular docking and in silico ADMET insights

This study presents an innovative green synthesis method for xanthene, benzoxanthene, and chromene derivatives using agar as a natural catalyst. Our method achieves high yields (up to 95%) with short reaction times (less than 1 hour) under environmentally friendly conditions and simple work-up procedures. The docking analysis conducted provides insights into the complex binding energies, molecular interactions, and hydrogen bond energies and distances. Molecular docking studies reveal strong chemical interactions with human serum albumin (HSA) and DNA gyrase, suggesting strong anticancer and antibacterial potential with binding energies ranging from -8.5 to -9.8 kcal/mol. In silico ADMET analysis and drug-likeness analysis confirm favorable pharmacokinetic properties, including high oral bioavailability and low toxicity. This work offers a sustainable and effective approach to developing new therapeutic agents.

Molecular Docking and ADMET Studies to Investigate Antioxidant Potency of New Amides of Piper retrofractum Vahl by Targeting Keap1 Inhibitor

Abstract Antioxidants are considered important in maintaining the balance of free radicals in the body due to exposure to air pollution. Piper retrofractum Vahl which is a traditional Indonesian medicinal herb which is said to have the characteristics of being an antioxidant in preventing free radicals in the body. Therefore, this research aims to investigate possible interactions between new amides of Piper retrofractum Vahl. and Keap1, one of the key proteins of the Keap1/Nrf2 pathway, the major system involved in redox regulation. Molecular docking study, using molecular mechanic calculations with Yasara to investigate binding energy and pkCSM to predict ADMET. Results this study showed that dipiperamides F has binding energy of 9.855 kcal/mol (closest to that of the crystallographic ligands), dipiperamides G (9.543 kcal/mol), piperodione (8.448 kcal/mol), (E)-N-cinnamoyl-2-methoxypiperidine (7.560 kcal/mol), (2E, 12E)-pipertride cadienamid (7.084 kcal/mol), N-isobutyl-(2E, 4E, 10Z)-hexadeca-2, 4, 10-trienamide (6.788 kcal/mol), (R)-1-(2-oxopyrrolidin-3-yl)-5, 6-dihydropyridin-2(1H)-one (6.524 kcal/mol), 2E, 14Z)-N-isobutyleicosa-2, 14-dienamide (5.116 kcal/mol). Visualization of receptors-ligands complex showed data on hydrogen bonds and no-covalen interactions, including hydrogen bond distances. Finally, ADMET (Adsorption, Desorption, Metabolism, Excretion, Toxicity) predictions and drug-likeness properties were performed on the tested compound. Our study indicates that new amides from Piper retrofractum Vahl may behave as potential natural antioxidant agents by targeting the Keap1 inhibitor.

6-Octadecenoic and Oleic Acid in Liquid Smoke Rice Husk Showed COVID-19 Inhibitor Properties.

In recent years, liquid smoke rice husk (LSRH) has shown its therapeutic potency to diabetes, wound healing, stomatitis, and periodontitis. The phenol, 6-octadecenoic acid, oleic acid, and 9-octadecanoic acid were responsible for their therapeutic effect. The LSRH also demonstrated their potential for infectious diseases such as coronavirus disease (COVID-19). Therefore, the molecular dynamics (MDs) simulation and pharmacophore analysis was performed to analyse the binding stability of 6-octadecenoic and oleic acid. Based on MD simulation, 6-octadecenoic and oleic acids seemed to retain their interactions with Ser144 and Thr24, respectively, with hydrogen bond distance less than 2.9 Å. This interaction was stable during the simulation and has hydrophobic and hydrogen bonds/acceptors. The 6-octadecenoic acid and oleic acid were confirmed to have great potency as inhibitors for COVID-19. These compounds also showed that the existence of hydrophobic and hydrogen bonds/acceptors could increase biological activity.

Potential acridinedione derivatives for the development of a heterobifunctional PROTAC for targeted degradation of PCSK9 protein

Proprotein convertase substilisin-like/kexin type 9 (PCSK9) interacts with the low-density lipoprotein (LDL) receptor by protein-protein interaction (PPI). The inhibition of this PPI lowers the LDL cholesterol levels, thereby reducing the risks of cardiovascular diseases. We identified in-house synthesized acridinedione scaffolds as binders of PCSK9 through microsecond timescale conventional and biased molecular dynamics (MD) simulations. The free energy of binding was calculated by the Molecular Mechanics Poisson-Boltzmann Surface Area and umbrella sampling methods for acridinedione molecules and compared with reference molecules (co-crystallized inhibitors). Three acridinedione molecules (DSPD-2, DSPD-4, and DSPD-6) were identified as potential binders of the PCSK9 allosteric binding site from preliminary docking and steered MD simulations. The stability of molecules inside the allosteric pocket was established by the low values of root mean square deviations of backbone C-α atoms. The acridinedione derivatives also showed a shorter distance of hydrogen bonds as compared to the standard molecules. The molecule DSPD-6 showed the lowest binding free energy as compared to other selected and standard molecules. The binding of the selected molecules at the allosteric binding pocket had no effect on structural parameters of LDL receptor-binding site of PCSK9 protein. Finally, a proteolysis targeting chimera (PROTAC) was developed by attaching a proteasome recruiting tag to DSPD-6 (lowest binding affinity) to achieve ligand-induced protein degradation. These results qualify the development of the DSPD-6 molecule as a heterobifunctional PROTAC for targeted degradation of PCSK9 protein. Moreover, our computational strategy provides a framework for the identification of molecules against conventionally undruggable PPI targets.

Comparing Microcrystal Electron Diffraction (MicroED) and X-ray crystallography as methods for structure determination of Oseltamivir phosphate

Oseltamivir phosphate is a pharmaceutical used in the treatment of influenza viruses. Panče Naumov et al. took two years of dedicated single crystal cultivation and successfully obtained low-quality single crystals through a diffusion method. Cultivation of Oseltamivir phosphate single crystals was proved to be difficult and can extend over several months or more. We employed microcrystalline electron diffraction (MicroED) for direct powder measurements, eliminating the need for lengthy single-crystal cultivation, and the time to obtain the molecular structure of Oseltamivir phosphate was shortened from several months to five hours. Comparative analyses of single crystal (Crystal 1) and MicroED (Crystal 2) results revealed equivalent crystal structures, with minimal differences in hydrogen bond distances, identical powder X-ray diffraction patterns, and negligible variations in Hirshfeld surface analysis. The differential scanning calorimetry (DSC) analysis showcased a higher melting point of Oseltamivir phosphate (206.0 °C) than Oseltamivir (110.7 °C), indicating that Oseltamivir phosphate had high temperature stability, and may result in the selection of Oseltamivir phosphate as a formulation form. The study establishes and verifies a congruence between MicroED detection and traditional single-crystal detection methods and may be applied in the elucidation of compound structures and the surveillance of drug polymorphism.

Computational Analysis of Lenalidomide and Pomalidomide Enantiomers' Binding Interactions With Prostaglandin (PG)-Protein: Implications for Inflammatory Activity in Cancer.

Lenalidomide and Pomalidomide are chiral immunomodulatory drugs (IMiDs) and have antiangiogenic and anti-immunomodulatory activity. Each enantiomer may have distinct binding and biological activity. This study aimed to explore the in-silico binding of both enantiomers of Lenalidomide and Pomalidomide with Prostaglandin and its potential impact on persisting inflammatory activity in cancer. This can further provide insight into the transport of pro-inflammatory mediators and their potential implications for the inflammatory microenvironment within tumors. Molecular docking studies were performed to explore the binding potential of both enantiomers of Lenalidomide and Pomalidomide with Pg protein. The crystal structure of Pg-protein (PDB ID: 1IW7) was obtained from the Protein Data Bank. The binding energies for (-)-Lenalidomide and (+)-Lenalidomide were -6.7 and -7.2 kcal/mol, respectively, while the binding energies for (-)-Pomalidomide and (+)-Pomalidomide were -7.8 and -8.1 kcal/mol, respectively. The binding mode analysis revealed that all four compounds formed hydrogen bonds with key amino acid residues of Pg-protein. The hydrogen bond distances for (-)-Lenalidomide, (+)-Lenalidomide, (-)-Pomalidomide, and (+)-Pomalidomide were 2.1 Å, 2.0 Å, 2.2 Å, and 2.1 Å, respectively. The present study suggests that both enantiomers of Lenalidomide and Pomalidomide have a high affinity for Pg-protein and can effectively target the Pg-protein pathway to persist inflammatory activity in cancer.By targeting inflammation-mediated processes, these drugs may offer a novel strategy to combat tumor progression.

RNA as a component of scrapie fibrils

Recently, electron cryo-microscopy (cryo-EM) maps of fibrils from the brains of mice and hamsters with five infectious scrapie strains have been published and deposited in the electron microscopy data bank (EMDB). As noted by the primary authors, the fibrils contain a second component other than protein. The aim of the present study was to identify the nature of this second component in the published maps using an in silico approach. Extra densities (EDs) containing this component were continuous, straight, axial, at right angles to protein rungs and within hydrogen-bonding distance of protein, consistent with a structural role. EDs co-located with strips of basic residues, notably lysines, and formed a conspicuous cladding over parts of the N-terminal lobe of the protein. A Y-shaped polymer consistent with RNA was found, in places forming a single chain and at one location forming a duplex, comprising two antiparallel chains, and raising the intriguing possibility of replicative behaviour. To reflect the monotonous nature of the protein interface, it is suggested that the RNA may be a short tandem repeat. Fibrils from brains of patients with Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and other neurodegenerations also contain EDs and may be of a similar aetiology.

Dynamic Insights into DNA Conformational Changes and the Impact of Magnesium Ions on Topoisomerase IA Enzymes: A Molecular Dynamics Simulation Study

Molecular dynamics simulations were employed to scrutinize the conformational changes in DNA strands and elucidate the influence of magnesium ions on Topoisomerase IA enzymes. Through the computation of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), hydrogen bond distances, dihedral angles, and Solvated Accessible Surface Area (SASA), we meticulously examined the structural dynamics. The results reveal intricate patterns of DNA strand alterations, showcasing the profound role of magnesium ions in modulating the behavior of Topoisomerase IA enzymes. This study contributes essential insights into the molecular mechanisms governing DNA conformational changes, offering a foundation for further understanding the biochemical intricacies of Topoisomerase IA enzyme function.

Temperature-dependent solid-state phase transition with twinning in the crystal structure of 4-meth-oxy-anilinium chloride.

At room temperature, the title salt, C7H10NO+·Cl-, is ortho-rhom-bic, space group Pbca with Z' = 1, as previously reported [Zhao (2009 ▸). Acta Cryst. E65, o2378]. Between 250 and 200 K, there is a solid-state phase transition to a twinned monoclinic P21/c structure with Z' = 2. We report the high temperature structure at 250 K and the low-temperature structure at 100 K. In the low-temperature structure, the -NH3 hydrogen atoms are ordered and this group has a different orientation in each independent mol-ecule, in keeping with optimizing N-H⋯Cl hydrogen bonding, some of which are bifurcated: these hydrogen bonds have N⋯Cl distances in the range 3.1201 (8)-3.4047 (8) Å. In the single cation of the high-temperature structure, the NH hydrogen atoms are disordered into the average of the two low-temperature positions and the N⋯Cl hydrogen bond distances are in the range 3.1570 (15)-3.3323 (18) Å. At both temperatures, the meth-oxy group is nearly coplanar with the rest of the mol-ecule, with the C-C-O-C torsion angles being -7.0 (2)° at 250 K and -6.94 (12) and -9.35 (12)° at 100 K. In the extended ortho-rhom-bic structure, (001) hydrogen-bonded sheets occur; in the monoclinic structure, the sheets propagate in the (010) plane.

Identification of natural antimicrobial peptides mimetic to inhibit Ca2+ influx DDX3X activity for blocking dengue viral infectivity.

Viruses are microscopic biological entities that can quickly invade and multiply in a living organism. Each year, over 36,000 people die and nearly 400 million are infected with the dengue virus (DENV). Despite dengue being an endemic disease, no targeted and effective antiviral peptide resource is available against the dengue species. Antiviral peptides (AVPs) have shown tremendous ability to fight against different viruses. Accelerating antiviral drug discovery is crucial, particularly for RNA viruses. DDX3X, a vital cell component, supports viral translation and interacts with TRPV4, regulating viral RNA metabolism and infectivity. Its diverse signaling pathway makes it a potential therapeutic target. Our study focuses on inhibiting viral RNA translation by blocking the activity of the target gene and the TRPV4-mediated Ca2+ cation channel. Six major proteins from camel milk were first extracted and split with the enzyme pepsin. The antiviral properties were then analyzed using online bioinformatics programs, including AVPpred, Meta-iAVP, AMPfun, and ENNAVIA. The stability of the complex was assessed using MD simulation, MM/GBSA, and principal component analysis. Cytotoxicity evaluations were conducted using COPid and ToxinPred. The top ten AVPs, determined by optimal scores, were selected and saved for docking studies with the GalaxyPepDock tools. Bioinformatics analyses revealed that the peptides had very short hydrogen bond distances (1.8 to 3.6Å) near the active site of the target protein. Approximately 76% of the peptide residues were 5-11 amino acids long. Additionally, the identified peptide candidates exhibited desirable properties for potential therapeutic agents, including a net positive charge, moderate toxicity, hydrophilicity, and selectivity. In conclusion, this computational study provides promising insights for discovering peptide-based therapeutic agents against DENV.

Intramolecular CH-Hydrogen Bonding During the Dissociation of the Oxaphosphetane Intermediate Facilitates Z/E-Selectivity in Wittig Olefination.

Herein, DFT studies corroborating experimental results revealed that the shortest intramolecular hydrogen bonding distance of cis/trans-oxaphosphetane (OPA) oxygen with the CH-hydrogen of a triphenylphosphine phenyl ring provides good evidence for the attained olefin Z/E-selectivity in Wittig olefination of the studied examples. 2-Nitrobenzaldehyde, 3-nitrobenzaldehyde, 2-nitro-3-bromobenzaldehyde, 2-nitro-5-bromobenzaldehyde and 2-nitro-5-arylbenzaldehydes provided Z-nitrostilbenes with (2-chloro-4-hydroxy-3-methoxy-5-(methoxycarbonyl)benzyl) triphenylphosphonium chloride as the major products. However, 4-nitrobenzaldehyde and 2-nitro-6-bromobenzaldehydes furnished E-nitrostilbenes as the major products in high yields. Furthermore, the DFT computed intramolecular CH1/CH2-hydrogen bond distances with Cl/NO2 of selected stilbene derivatives were in good agreement with intramolecular hydrogen bond distances measured from single-crystal X-ray diffraction measurements.

A red emissive covalently bonded graphene quantum dot-Tetraaminophenylporphyrin hybrid as a probe for the sensing of L-proline

L-Proline, the exclusive secondary amino acid with proteinogenic properties, is a vital contributor to body metabolism and the maintenance of muscle repairs, playing a pivotal role in numerous physiological processes in the human body. However, the current understanding of proline sensing is limited. In this study, we have used Tetraaminophenylporphyrin (TAPP) covalently functionalized graphene quantum dot (GQD) as a probe for the selective and sensitive detection of L-Proline. Analytical studies carried out under the optimized conditions reveal a good linear range of 9.8×10−5 M to 3.5×10−3 M with 1.6×10−7 M limit of detection. Photophysical studies reveal a ground state complex formation between the probe and proline which is responsible for the turn-off behaviour. This is not present in the case of the individual components GQD and TAPP separately which highlights the importance of covalent functionalization. The stabilization energy of the complex between the probe and different aminoacids and the corresponding hydrogen bond distances between these two moieties were calculated theoretically using density functional theory. This corroborates the enhanced stability of complex formation and the selectivity of probe towards proline compared to other aminoacids. The practical utility of the developed probe for the detection of proline in real samples like commercial milk and artificial urine is also demonstrated by spike recovery analysis which results in a recovery percent and RSD values within the acceptable limit.

Effect of the mixture composition of BmimBF4/PC on the solvation structure of C153 in as seen from molecular dynamics study

In this work we report the results of the molecular dynamics (MD) simulation of the effect of the mixture composition of 1-butyl-3-methylimidazolium terafluoroborate (BmimBF4) and propylene carbonate (PC) on the solvation structure of coumarin 153.For this purpose, the local structure around C153 was characterized using distance and angle descriptors of the C-H…A configuration. They are based on the calculation of the nearest neighbor radial distributions between the C or H atoms of one component of the solution (C153, PC, Bmim+) and the electronegative A atoms (F, O) of the other ones. We also considered the combined distribution functions that include the radial and the orientation between the ring of either the cation or the solvent and that of C153.Our results show that in neat ionic liquid, the BF4− anion and in particular its F atoms, is, as expected, located close to the hydrogen atoms of the C153, while the cation, in particular its ring hydrogen atoms, are located close to the F and O atoms of the C153 and its ring has an almost the above/below parallel orientation with respect to the C153 lactone ring. In neat PC, its O atoms are located in the direct environment of the H atoms of C153 and concomitantly, its ring has the above/below parallel orientation with respect to the C153 rings. By comparing the distance and angle descriptors values of the C-H…A configuration, with a threshold hydrogen bond distance 0.30 nm and an angle of 151°, we were able to rank the C-H…A interactions as weak hydrogen bonds. Furthermore, in the excited state, noticeable changes in charge values on the H, F and O atoms of C153, occurs and as a consequence, the radial distribution of the anion, cation and the solvent around these atoms of C153 is more affected.At the mixture composition around 0.20 mol fraction of BmimBF4, the behavior of the distance angle descriptors of the solvation of C153, indicates a cross over between the situation where solvation is dominated by the ions to that dominated by the solvent molecules. In the excited state of C153, the distance descriptor values are slightly decreasing with respect to those in the ground state while the angle descriptor values remain almost the same.

Spectroscopic and computational studies of the noncovalent interactions in the structures of the 2-hydroxy-3-iodo-6-methoxybenzenecarbonyl (-C(O)CH3, -CHO) derivatives

The structures of 2‑hydroxy-3-iodo-6-methoxyacetophenone 2a and 2‑hydroxy-3-iodo-6-methoxybenzaldehyde 2b were elucidated using a combination of NMR, IR and UV–Vis spectroscopic techniques complemented with single crystal X-ray diffraction analysis. XRD confirmed the presence of thermodynamically more favourable six-membered intramolecular hydrogen bonding motif designated as S(6) in the graph-set assignments involving interaction between OH (donor) and an oxygen atom (acceptor) of the carbonyl group with hydrogen bond distance, O(2)-H(2)⋯O(1) of 2.463(2) Å and 2.606(2) Å for 2a and 2b, respectively. The halogen bonding affinity of the iodine atom of 2a as a representative model was investigated in the solution phase by 13CNMR spectroscopy in various deuterated solvents (CDCl3, DMSO‑d6, pyridine-d5 & benzene-d6) and also in benzene-d6 in the presence of triethylamine (Et3N) as a Lewis base. XRD analysis determined that the iodine atom of 2b is involved in two main types of halogen bonding, namely C–I⋯O and halogen-halogen (C–I⋯I–C) contacts. The C–I⋯π and intermolecular C–I⋯O–H contacts were observed in the case of 2a. The DFT calculations were also performed in the gas phase to correlate the experimental results with the simulated data.

The unusual (syn-/anti-)2 conformation of a di-meth-oxy-pyrimidyl-based tennimide.

The tennimide macrocycle, (I) (C52H40N16O16.0.167H2O), was synthesized from 2-amino-4,6-di-meth-oxy-pyrimidine and pyridine-2,6-dicarbonyl dichloride. Compound (I) represents the first tennimide incorporating pyridine rings in the macrocycle scaffold. In the macrocycle ring, the carbonyl groups at each successive dicarbon-yl(pyridine) moiety adopt the (syn/anti)2 conformation. This contrasts with all previously reported tetra-imide macrocycles, which exhibit the (syn)4 conformation. The effect is to close any potential cavity or niche by having two of the central pyridine C5N rings aligned close to each other [with closest pyridine Cg⋯Cg ring centroid separations of 3.5775 (19) Å; closest C⋯C = 3.467 (5) Å]. A partial occupancy water mol-ecule (with s.o.f. = 0.167), resides with its oxygen atom on a twofold axis at hydrogen-bonding distances to the carbonyl O atom, in a mol-ecular niche between two pyridine rings. Macrocyles of (I) have all six C=O groups and all eight meth-oxy O atoms present on the macrocycle surface. However, all twelve N atoms are effectively shielded on steric grounds from any potential inter-molecular inter-actions. The remaining two C=O O atoms inter-act with the partial occupancy water mol-ecule via two O-H⋯O=C hydrogen bonds. Macrocycles of (I) stack as one-dimensional chains along the b-axis direction with primary inter-molecular inter-actions involving weak C-H⋯O=C/OCH3/H2O contacts. Chains inter-lock weakly via meth-oxy-meth-oxy C-H⋯O inter-actions into two-dimensional sheets.

Correlation between Si-Al disorder and hydrogen-bonding distance variation in ussingite (Na2AlSi3O8OH) revealed by one- and two-dimensional multi-nuclear NMR and first-principles calculation

Abstract Ussingite (Na2AlSi3O8OH) is a mineral with a unique interrupted framework structure and strong hydrogen bonding. It contains 4-, 6-, and 8-membered tetrahedral rings resembling feldspars, but, unlike the latter, is partially depolymerized. There are four crystallographically distinct tetrahedral (T) sites, two of which (T1, T2) are Q4 [i.e., having 4 next nearest neighbor (NNN) T sites], and the other two (T3, T4) are Q3 (i.e., having 3 NNN T sites), each with NNN (in brackets) of T1(1T2, 1T3, 2T4), T2(1T1, 2T3, 1T4), T3(1T1, 2T2), and T4(2T1, 1T2). There is one unique OH site in the T4-O8-H···O2-T3 configuration, where O8 and O2 are nonbridging O atoms (NBO). In the ordered structure, T1 is fully occupied by Al, and the other three T sites by Si. Previous X-ray and neutron diffraction and 1H and 29Si NMR studies gave contradictory conclusions regarding Si-Al disorder. In this study, we were able to unambiguously clarify the issue via comprehensive one- and two-dimensional 1H, 29Si, 27Al, and 23Na NMR and first-principles calculation. It was revealed that there is ~3% Si-Al disorder that occurs between neighboring T1-(O)-T2 sites, such that the formation of Al-O-Al linkage and Al(Q3) are avoided. The disorder was found to result in the development of Si(Q3) sites with various NNN, including 3Al and 3Si, and neighboring OH sites having significantly shorter and longer hydrogen-bonding distances than in the ordered structure, with 1H chemical shifts near 15~16 ppm and 11 ppm, in addition to a main peak near 13.9 ppm. Good correlation was found between 1H chemical shift, hydrogen-bonding (O-H, H···O, and O···O) distances, and Si-O distances in the Si-O-H···O-Si linkage. This suggests that Si-Al disorder is correlated with variation in hydrogen-bonding distances via through-bond transmission of bond valence variations. This could be a universal phenomenon also applicable to other hydrous minerals. The revelation of preferential partition of Al in Q4 over Q3 sites to avoid the formation of Al-OH and Al-NBO provides insight into their behavior in other partially depolymerized hydrous aluminosilicate systems, such as glasses and melts.

Improving thermostability of a PL 5 family alginate lyase with combination of rational design strategies

Alginate lyases with strict substrate specificity possess potential in directed production of alginate oligosaccharides with specific composition. However, their poor thermostability hampered their applications in industry. In this study, an efficient comprehensive strategy including sequence-based analysis, structure-based analysis, and computer-aid ΔΔGfold value calculation was proposed. It was successfully performed on alginate lyase (PMD) with strict poly-β-D-mannuronic acid substrate specificity. Four single-point variants A74V, G75V, A240V, and D250G with increased Tm of 3.94 °C, 5.21 °C, 2.56 °C, and 4.80 °C, respectively, were selected out. After ordered combined mutations, a four-point mutant (M4) was finally generated which displayed remarkable increase on thermostability. The Tm of M4 increased from 42.25 °C to 51.59 °C and its half-life at 50 °C was about 58.9-fold of PMD. Meanwhile, there was no obvious loss of enzyme activity (more than 90% retained). Molecular dynamics simulation analysis insisted that the improvement of thermostability might be attribute to the rigidified region A which might be caused by the newly formed hydrogen bonds and salt bridges introduced by mutations, the lower distance of original hydrogen bonds, and the more compact overall structures.

Dynamics simulation of excited-state proton transfer reactions of 8-hydroxyquinoline with water clusters: A TD-DFT study

Detailed pictures of the excited-state proton transfer reactions of 8-hydroxyquinoline (8HQ) and its small clusters of water have been systematically investigated using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods at B3LYP/TZVP and TD-B3LYP/TZVP level of theory, respectively. Intramolecular hydrogen bond (intraHB) and intermolecular hydrogen bond (interHB) interactions between 8HQ and water cluster become stronger in the first excited state (S1), confirmed by hydrogen bond distances and topological analysis. In addition, TD-B3LYP dynamics simulations have been elucidated and revealed that excited-state intramolecular proton transfer (ESIntraPT) and multiply excited-state intermolecular proton transfer (ESInterPT) reactions of these complexes can take place in the ultrafast time scale of femtoseconds. Increasing the number of water molecules may give rise to a barrier energy that is anti-correlated to the probability of tautomer species from phototautomerization, especially in 8HQ-W1 and 8HQ-W1+1. Moreover, water molecules initiate multiple proton transfer occurring through two- and three-step ESInterPT namely excited-state double proton transfer (ESDPT) and excited-state triple proton transfer (ESTPT) in which the interHBs are formed by rearrangement of water molecules of 8HQ-W2. This circumstance takes a longer time (up to 470 fs) compared to that of ESIntraPT. Thus, the simulated results from this study could provide insight into ESIntraPT and ESInterPT of phototautomerization and the significant photodynamics which could not be found from the experimental aspects of 8HQ and its solvent clusters.