Intramolecular Bond Research Articles

Investigating the molecular origins of deformation in polyurea

This paper discusses some of the fundamental mechanisms of atomic-scale deformation associated with inter and intramolecular bond forces under applied loads in polyurea, through simulations using a detailed all-atom molecular dynamics model. The study demonstrates the evolution of conformational changes in the polymer molecular structure, as well as how internal variables associated with bond length, bond angle, bond dihedral, chain entanglements of the soft regime of the molecule, and free volume evolve with tensile loading at high strain-rates. Furthermore, it explores the effect of strain rates, simulation constraints, and nanofillers (buckyballs) on the overall polyurea response and properties. The observations made in this study can be used in the design of materials that can exhibit superior performance in extreme environments.

Crystal structure of the AlbEF complex involved in subtilosin A biosynthesis

Subtilosin A is a sactipeptide bacteriocin produced by Bacillus subtilis strain 168, containing intramolecular thioether bonds and a head-to-tail macrocyclic peptide bond. Macrocyclization is presumably catalyzed by AlbE and AlbF proteins encoded by the subtilosin A biosynthesis gene cluster. However, the underlying mechanism of macrocyclization remains uncertain as the tertiary structures of the proteins are undetermined. Here, we report the crystal structures of AlbE and AlbF homologs in Quasibacillus thermotolerans, wherein the subtilosin biosynthesis gene cluster is highly conserved. Structural analysis and pull-down assays revealed that AlbE and AlbF form heterodimeric complexes. Although the AlbEF complex shows structural similarity to M16B family metalloproteases, the substrate-binding chamber is shallower and more open than the other M16B family proteins. The chamber surface showed electrostatic complementarity to the precursor of subtilosin. Our findings provide insights into the role of AlbEF in metalloprotease catalysis and macrocyclic peptide bond formation.

Recent Advances in Organic Room-Temperature Phosphorescence of Heteroatom (B/S/P)-Containing Chromophores

Recent Advances in Organic Room-Temperature Phosphorescence of Heteroatom (B/S/P)-Containing Chromophores

Structural, vibrational and electronic properties of some tetrel-bonded complexes of the fluorinated methanes methyl fluoride, difluoromethane and fluoroform: an ab initio study.

A search has been conducted, by means of ab initio molecular orbital theory, for potential tetrel-bonded complexes formed between the fluorinated methanes methyl fluoride, difluoromethane and fluoroform, and the related hydrides ammonia, water, hydrogen fluoride, phosphine, hydrogen sulphide and hydrogen chloride. Eleven such complexes have been identified, six containing CH3F and five CH2F2. The complexes are typically less strongly bound than their hydrogen-bonded counterparts, and the interaction energies vary in a consistent way with the periodic trend of the electron donors. The intermolecular separations and changes of the relevant intramolecular bond lengths, the wavenumber shifts of the critical vibrational modes and the extents of charge transfer correlate, by and large, with the strengths of interaction.

Structure of novel N-fluorosilylmethyl-N-isopropylureas

Novel N-isopropyl-N',N'-dimethyl-N-(silylmethyl)ureas Me2NC(O)N(Pri)CH2SiMenX3–n (X = OEt, F; n = 0–2) were synthesized, and their structure was confirmed by 1H, 13C and 29Si NMR spectroscopy. According to NMR data, the silicon atom of the fluorosilanes (X = F) is pentacoordinated. The X-ray diffraction analysis of the (trifluorosilyl)methylcontaining urea showed that it exists as (O–Si) chelate with intramolecular dative bond C=O→Si (1.880 Å).

Visible-light-induced photocatalyst-free intramolecular sp3 C–H oxidation of 2‑alkyl benzamides

A new amidyl radical-mediated intramolecular 2‑alkyl benzamide oxidation reaction was developed under mild photochemical conditions. This Hofmann–Löffler–Freytag (HLF) type reaction involved the formation of intramolecular sp3 CO bonds via a different pathway than the construction of CN bonds in classic and modified HLF reactions. The oxidation proceeded smoothly at room temperature without any photocatalyst, and the desired products were provided in moderate to excellent yields with exclusive chemoselectivity.

New Fmoc-Amino Acids/Peptides-Based Supramolecular Gels Obtained through Co-Assembly Process: Preparation and Characterization.

One of the methods of obtaining supramolecular gels consists of the possibility of self-assembly of low molecular weight gelators (LMWGs). However, LMWG-based gels are often difficult to handle, easy to destroy and have poor rheological performance. In order to improve the gels’ properties, the LMWGs molecules are co-assembled, which induces more cross-links with more stable structures. Starting from these aspects, the present study refers to the preparation of a bionic hydrogel stabilized with a physiologically occurring, bifunctional biomolecule, L-lysine, co-assembled with other amino acids or peptides (such as a modified amino acid (Fmoc-serine or Fmoc-glutamic acid) or a tripeptide (Fmoc-Gly-Gly-Gly)) with the potential to support the repair of injuries or the age-related impaired structures or functions of living tissues. The introduction of a copartner aims to improve hydrogel characteristics from a morphological, rheological and structural point of view. On the other hand, the process will allow the understanding of the phenomenon of specific self-association and molecular recognition. Various characterization techniques were used to assess the ability to co-assemble: DLS, FT-IR, SEM and fluorescence microscopy, rheology and thermal analysis. Studies have confirmed that the supramolecular structure occurs through the formation of inter- and intramolecular physical bonds that ensure the formation of fibrils organized into 3D networks. The rheological data, namely the G′ > G″ and tan δ approximately 0.1–0.2 gel-like behavior observed for all studied samples, demonstrate and sustain the appearance of the co-assembly processes and the ability of the samples to act as LMWG. From the studied systems, the Fmoc–Lys–Fmoc_ Fmoc–Glu sample presented the best rheological characteristics that are consistent with the observations that resulted from the dichroism, fluorescence and SEM investigations.

Chalcogen bond-guided conformational isomerization enables catalytic dynamic kinetic resolution of sulfoxides

Conformational isomerization can be guided by weak interactions such as chalcogen bonding (ChB) interactions. Here we report a catalytic strategy for asymmetric access to chiral sulfoxides by employing conformational isomerization and chalcogen bonding interactions. The reaction involves a sulfoxide bearing two aldehyde moieties as the substrate that, according to structural analysis and DFT calculations, exists as a racemic mixture due to the presence of an intramolecular chalcogen bond. This chalcogen bond formed between aldehyde (oxygen atom) and sulfoxide (sulfur atom), induces a conformational locking effect, thus making the symmetric sulfoxide as a racemate. In the presence of N–heterocyclic carbene (NHC) as catalyst, the aldehyde moiety activated by the chalcogen bond selectively reacts with an alcohol to afford the corresponding chiral sulfoxide products with excellent optical purities. This reaction involves a dynamic kinetic resolution (DKR) process enabled by conformational locking and facile isomerization by chalcogen bonding interactions.

In silico analysis of the C-terminal domain of big defensin from the Pacific oyster

Defensins are antimicrobial peptides consisting of intramolecular disulphide bonds in a complex folded arrangement of two or three antiparallel β-sheets with or without an α-helical structure. They are produced by a vast range of organisms being constitutively expressed or induced in various tissues against different stimuli like infection, injury or other inflammatory factors. Two classes of invertebrate defensin exist, namely CS-αβ and big defensin, the latter being predominantly present in molluscs. Intriguingly, an invertebrate big defensin gene has been hypothesized as the most probable ancestor of vertebrate β-defensins. Here, conserved residues were identified for both big defensin and β-defensin. In silico mutation on conserved amino acid positions of the β-defensin-like domain of big defensin from Crassostrea gigas was carried out to understand the effects of mutation on the structure and function of the protein. R64A and E71A have been identified as deleterious as well as destabilizing for the protein. Changes in amino acid network and aggregation propensity were also observed upon mutating these two charged residues. 100 ns molecular dynamics simulations of wild-type, R64A and E71A structures revealed significant conformational changes in the case of mutants. Furthermore, molecular docking highlighted the significance of R64 in ligand interaction. In conclusion, these results provide the first in-depth understanding of the structural and functional importance imparted by two conserved charged residues in the C-terminal region of big defensin. It also enhances the existing knowledge about this antimicrobial peptide for application in therapeutics and other aspects of protein engineering. Communicated by Ramaswamy H. Sarma

Intramolecular Covalent Bonds in Gram-Positive Bacterial Surface Proteins.

Gram-positive bacteria experience considerable mechanical perturbation when adhering to host surfaces during colonization and infection. They have evolved various adhesion proteins that are mechanically robust to ensure strong surface adhesion. Recently, it was discovered that these adhesion proteins contain rare, extra intramolecular covalent bonds that stabilize protein structures and participate in surface bonding. These intramolecular covalent bonds include isopeptides, thioesters, and ester bonds, which often form spontaneously without the need for additional enzymes. With the development of single-molecule force spectroscopy techniques, the detailed mechanical roles of these intramolecular covalent bonds have been revealed. In this review, we summarize the recent advances in this area of research, focusing on the link between the mechanical stability and function of these covalent bonds in Gram-positive bacterial surface proteins. We also highlight the potential impact of these discoveries on the development of novel antibiotics and chemical biology tools.

A Bond-Energy/Bond-Order and Populations Relationship.

We report an analytical bond energy from bond orders and populations (BEBOP) model that provides intramolecular bond energy decompositions for chemical insight into the thermochemistry of molecules. The implementation reported here employs a minimum basis set Mulliken population analysis on well-conditioned Hartree-Fock orbitals to decompose total electronic energies into physically interpretable contributions. The model's parametrization scheme is based on atom-specific parameters for hybridization and atom pair-specific parameters for short-range repulsion and extended Hückel-type bond energy term fitted to reproduce CBS-QB3 thermochemistry data. The current implementation is suitable for molecules involving H, Li, Be, B, C, N, O, and F atoms, and it can be used to analyze intramolecular bond energies of molecular structures at optimized stationary points found from other computational methods. This first-generation model brings the computational cost of a Hartree-Fock calculation using a large triple-ζ basis set, and its atomization energies are comparable to those from widely used hybrid Kohn-Sham density functional theory (DFT, as benchmarked to 109 species from the G2/97 test set and an additional 83 reference species). This model should be useful for the community by interpreting overall ab initio molecular energies in terms of physically insightful bond energy contributions, e.g., bond dissociation energies, resonance energies, molecular strain energies, and qualitative energetic contributions to the activation barrier in chemical reaction mechanisms. This work reports a critical benchmarking of this method as well as discussions of its strengths and weaknesses compared to hybrid DFT (i.e., B3LYP, M062X, PBE0, and APF methods), and other cost-effective approximate Hamiltonian semiempirical quantum methods (i.e., AM1, PM6, PM7, and DFTB3).

Sensitivity Analysis of the Catalysis Recombination Mechanism on Nanoscale Silica Surfaces.

A deep understanding of surface catalysis recombination characteristics is significant for accurately predicting the aeroheating between hypersonic non-equilibrium flow and thermal protection materials, while a de-coupling sensitivity analysis of various influential factors is still lacking. A gas–solid interface (GSI) model with a hyperthermal flux boundary was established to investigate the surface catalysis recombination mechanisms on nanoscale silica surfaces. Using the reactive molecular dynamics (RMD) simulation method, the effects of solid surface temperature, gas incident angle, and translational energy on the silica surface catalysis recombination were qualified under hyperthermal atomic oxygen (AO), atomic nitrogen (AN), and various AN/AO gas mixtures’ influence. It can be found that, though the Eley–Rideal (E–R) recombination mechanism plays a dominant role over the Langmuir–Hinshelwood (L–H) mechanism for all the sensitivity analyses, a non-linear increasing pattern of AO recombination coefficient γO2 with the increase in incident angle θin and translational energy Ek is observed. Compared with the surface catalysis under hyperthermal AO impact, the AN surface adsorption fraction shows an inverse trend with the increase in surface temperature, which suggests the potential inadequacy of the traditional proportional relationship assumptions between the surface adsorption concentration and the surface catalysis recombination coefficient for other species’ impact instead of AOs. For the incoming bi-component AO/AN gas mixtures, the corresponding surface catalysis coefficient is not the simple superposition of the effects of individual gases but is affected by both the intramolecular bond energies (e.g., O2, N2) and intermolecular energies (e.g., Si/N, Si/O).

High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies.

Nowadays, proteins and polysaccharides play a fundamental role in the manufacturing of biocompatible materials applied in food packaging. The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. The dynamic mechanical measurements were realized taking into account the parameters of temperature and relative humidity. The results indicate a significant change in the viscosity of the protein–polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs.

Structure Elucidation, Hirshfeld Surface Analysis, Molecular Docking and Computational Studies of a Jahn-Teller Distorted Octahedral Cobalt (II) Complex with Saccharin Ligand

A Jahn-Teller distorted octahedral cobalt(II) complex with saccharin and water ligands was synthesized and characterized using single-crystal X-ray diffraction, density functional theory calculation, surface analysis (MEP and Hirshfeld) and molecular docking studies. Co(II) center is six-coordinated in a distorted octahedral arrangement, with the two water O atoms located in the axial positions, and the two water O atoms and the saccharin N atoms located in the equatorial plane. Theoretical molecular modeling was carried out with Density Functional Theory (DFT) using UB3LYP with hybrid function LANL2DZ. To support intra-molecular and inter-molecular bondings in crystal structure, molecular electrostatic potential (MEP) and Hirshfeld surfaces are generated and visualized. The molecular docking analysis was investigated between cobalt complex ligand and the receptor of breast cancer mutant PDB: 3HB5-oxidoreductase.

Kinetics and Reaction Mechanism of Biothiols Involved in SNAr Reactions: An Experimental Study

Few kinetic parameters, or reaction rates, are known up to date in detail about 1-chloro and 1-fluoro-2,4-dinitrobenzene (ClDNB and FDNB, respectively) with a series of biothiols in aqueous media. These biological nucleophiles with thiol groups have been widely used as a reference in nucleophile reactivity assays due to their prevalence and cellular abundance. The main aim of this study was to elucidate the reaction mechanism based on Brönsted-type plots and reactivity patterns of the electrophile/nucleophile pairs. A complete kinetic study was performed in terms of the comparison of Brönsted-type slope parameters (β nuc) for the reactions and was used for assigning the mechanism and the rate-determining step associated with the reaction route. A mass spectrometry analysis demonstrated that the nucleophilic center of the biothiols is the -SH group and there is only one kinetic product. The kinetic study suggests that the reaction mechanism might be the borderline between concerted and stepwise pathways. An amine–enol equilibrium for the most reactive nucleophiles appears to be the main determining factor controlling the nucleophilic attack in the nucleophilic aromatic substitution reactions investigated, highlighting the anionic form for these nucleophiles. This amine–enol equilibrium involves a hydrogen bond which stabilizes the intermediate species in the reaction pathway. Thus, intramolecular bonds are formed and enhance the nucleophilic strength through the contribution of the solvent surrounding the electrophile/nucleophile pairs. Finally, we highlight the importance of the formation of electrophile/nucleophile adducts that could modify structures and/or functions of biological systems with potential toxic effects. Therefore, it is essential to know all these kinetic and reactivity patterns and their incidence on other studies.

Competition between Intra and Intermolecular Pnicogen Bonds: Complexes between Naphthalene Derivatives and Neutral or Anionic Bases.

The PnF2 (Pn=P,As,Sb,Bi) on a naphthalene scaffold can engage in an internal pnicogen Pn⋅⋅⋅N bond (PnB) with an NH2 group placed close to it on the adjoining ring. An approaching neutral NH3 molecule can engage in a second PnB with the central Pn, which tends to weaken the intramolecular bond. The presence of the latter in turn weakens the intermolecular PnB with respect to that formed in its absence. Replacement of the external NH3 by a CN- anion causes a fundamental change in the bonding pattern, producing a fourth covalent bond with Pn, which rearranges into a trigonal bipyramidal motif. This addition disrupts the internal Pn⋅⋅⋅N pnicogen bond, recasting the PnF2 ⋅⋅⋅NH2 interaction into an NH⋅⋅⋅F H-bond.

Molecular dynamics simulation study of NH4+ and NH2- in liquid ammonia: interaction potentials, structural and dynamical properties.

We provide tailor-made GAFF2-type interaction potentials for modeling ammonium and amide ions in ammonia. Based on harmonic approximation of intra-molecular bond stretching and bending, our force fields nicely reproduce the vibrational modes of NH4+ and NH2-, respectively. Moreover, quantum calculations of pair-wise NH4+/NH2--NH3 interactions were used for inter-molecular force field parameterization, while (NH3)n, [(NH4)(NH3)n]+, and [(NH2)(NH3)n]- complexes with n > 2, respectively, were reserved for benchmarking in terms of both structure and formation energy. Despite the limited reliability of molecular mechanics models for describing dimer complexes (n = 1), we find that GAFF2 reasonably reproduces [(NH4)(NH3)n]+ species for n = 2-4. For the assessment of [(NH2)(NH3)n]- complexes with n = 2-4, we however suggest the introduction of specific van der Waals parameters for amide-ammonia interactions. The application of the (extended) GAFF2 models is demonstrated for the study of ammonium and amide solvation in liquid ammonia at 240K and 1atm, respectively. On this basis, we suggest the applicability of our model for both gas phase and liquid states of ammonia.

New insights into the excited state intramolecular proton transfer (ESIPT) competition mechanism for different intramolecular hydrogen bonds of Kaempferol and Quercetin in solution

In this work, the process of the Excited State Intramolecular Proton Transfer (ESIPT) competition of Kaempferol and Quercetin in methanol was studied by means of the Density Functional Theory (DFT) and the Time-Dependent Density Functional Theory (TDDFT) method. Two different ESIPT reaction pathways were analyzed by the variation trend of the 3D potential energy surfaces (PESs) with the change of the intramolecular hydroxyl bond length through the PESs of the two molecules of the ground state (S0) and the first excited (S1) state. The ESIPT process only occurred between O25–H28 and O22–H28 and was completed within 33.1fs by molecular excited state dynamics simulation. It is demonstrated that when there are two kinds of hydrogen bonds in the molecule, the ESIPT prefers the six-membered ring hydrogen bonds to the five-membered ring hydrogen bonds.

Synergistic Generation and Accumulation of Triplet Excitons for Efficient Ultralong Organic Phosphorescence.

The traditional method to achieve ultralong organic phosphorescence (UOP) is to hybrid nπ* and ππ* configurations in appropriate proportion, which are contradictory to each other for improving efficiency and lifetime of phosphorescence. In this work, through replacing the electron-donating aromatic group with a methoxy group and combining intramolecular halogen bond to promote intersystem crossing and suppress non-radiative transition, an efficient UOP molecule (2Br-OSPh) has been synthesized with the longest lifetime and brightest UOP among its isomers. As compared to CzS2Br, which has a similar substituted position of bromine atom and a larger kisc (the rate of intersystem crossing), the smaller ΔETT* (the energy gap between monomeric phosphorescence and aggregated state phosphorescence) in 2Br-OSPh could accelerate the transition from T1 to T1 *. This research indicates that both generation and accumulation of triplet excitons play an important role in realizing efficient UOP materials.

PatcHwork: a user-friendly pH sensitivity analysis web server for protein sequences and structures.

pH regulates protein function and interactions by altering the charge of individual residues causing loss or gain of intramolecular noncovalent bonds, which may lead to structural rearrangements. While tools to analyze residue-specific charge distribution of proteins at a given pH exist, currently no tool is available to investigate noncovalent bond changes at two different pH values. To make protein pH sensitivity analysis more accessible, we developed patcHwork, a web server that combines the identification of amino acids undergoing a charge shift with the determination of affected noncovalent bonds at two user-defined pH values. At the sequence-only level, patcHwork applies the Henderson–Hasselbalch equation to determine pH-sensitive residues. When the 3D protein structure is available, patcHwork can be employed to gain mechanistic understanding of the effect of pH. This is achieved using the PDB2PQR and PROPKA tools and noncovalent bond determination algorithms. A user-friendly interface allows visualizing pH-sensitive residues, affected salt bridges, hydrogen bonds and aromatic (pi–pi and cation–pi) interactions. patcHwork can be used to identify patches, a new concept we propose of pH-sensitive residues in close proximity on the protein, which may have a major impact on function. We demonstrate the attractiveness of patcHwork studying experimentally investigated pH-sensitive proteins (https://patchwork.biologie.uni-freiburg.de/).