Effect Of Conformational Changes Research Articles

Environmental stress-induced conformational transitions modulate foaming and gelation properties of glycosylated egg white proteins

Glycosylation induces covalent grafting, resulting in conformational shifts that modulate the functional properties of proteins. This study examines the effect of conformational changes on the foaming and gelation properties of d-xylose glycosylated egg white protein (G-EWP) under different pH, ionic strength, and temperature conditions. Glycosylation end-products content increases initially, then reduces with increasing temperature while negatively correlating with pH and NaCl concentration. Treatment with NaCl induces electrostatic shielding on the G-EWP surface, decreasing the absolute value of ζ-potential from 19.63 mV to 14.9 mV. Temperature promotes thermal denaturation and macromolecular aggregation of G-EWP, increasing the particle size significantly from 523.9 nm to 4458.92 nm. Spectroscopic and protein structure analyses show that different environmental stresses alter the conformational structure of G-EWP, causing the rearrangement of amino acid residues. High temperature exerts a more pronounced effect on the secondary structure of G-EWP compared to variations in pH and NaCl, where the α-helices decline from 40.37% to 7.83% and the β-turns content increases from 19.30% to 39.57%. Reheating at 60 °C and acid treatment significantly increase the gel hardness, and the foaming capacity of G-EWP declines gradually with increasing pH and NaCl concentration, but improves with increasing temperature. Correlation analysis reveals that the molecular flexibility, β-sheet and β-turns effectiveness regulate the foaming capacity, and the charge variation positively modulates the gel properties of G-EWP.This study provides insight into regulating the functional properties of G-EWP effectively in industrial applications.

Binding of Selected Aroma Compounds to Myofibrillar Protein, Sarcoplasmic Protein, and Collagen during Thermal Treatment: Role of Conformational Changes and Degradation of Proteins.

To investigate the effects of conformational changes and thermal degradation of myofibrillar protein (MP), sarcoplasmic protein (SP), and collagen (CO) on the binding ability for aroma compounds during heating. Using SDS-PAGE, HPLC, and LC-MS/MS, a consistent rise in the total concentration of peptides and free amino acids formed by the thermal degradation of proteins was observed. The surface hydrophobicity, total sulfhydryl content, particle size, and secondary structure content of proteins changed significantly over time. Furthermore, the aroma binding ability of proteins was determined by gas chromatography-mass spectrometry. The results revealed an increase in binding ability during 5 or 10 min of heating due to protein unfolding and the accumulation of degradation products. However, the binding ability decreased due to protein aggregation with prolonged heating. Notably, all proteins exhibited strong affinity toward (E)-2-octenal, (E,E)-2,4-decadienal, 2-methyl-3-furanthiol, and dimethyl trisulfide. The binding ability of MP and SP was similar but differed significantly from that of CO, which had lower binding ability for hexanal, (E)-2-octenal, (E,E)-2,4-decadienal, and dimethyl trisulfide compared to MP and SP.

Quantum mechanical assessment on the optical properties of capsanthin conformers.

As optical properties, the ultraviolet-visible (UV-Vis) absorption spectra of capsanthin-based red natural dye are a decisive parameter for their usage in various applications. Thus, accurately predicting the maximum UV-Vis wavelength ( ) values is critical in designing dye-conjugated material. Extensive metadynamics simulations were carried out to generate capsanthin conformers at various levels of the extended tight-binding method. Benchmarking the time-dependent density-functional theory (TD-DFT) methods help understand the results of a particular functional and allows a comparison between results obtained with different functional. The long-range correction (LC) scheme in LC-TD-DFT-D4/ωB97X/def2-SVP has been found to reproduce the experimental and exhibited the effect of conformational changes to the calculated wavelengths. On the other hand, an inexpensive yet efficient LC-TD-DFTB method reproduced the experimental insensitive to conformational changes.

Impact of Semiochemicals Binding to Fel d 1 on Its 3D Conformation and Predicted B-Cell Epitopes Using Computational Approaches.

The major cat allergen Fel d 1 is a tetrameric glycoprotein from the secretoglobin superfamily. Fel d 1's biological role is unknown, but it has been previously shown that it participates in semiochemical binding/transportation. Fel d 1 has linear epitopes, but its conformational epitope sites remain unclear. In this study, we predicted the B-cell epitopes of Fel d 1 and explored semiochemical dynamics with epitopes using bioinformatics tools. The epitope residues were tabulated for chains 1 and 2 and the heterodimers of Fel d 1. The residual interactions of Fel d 1 with IgE were evaluated, and the prominent epitope sites were predicted. The molecular dynamics simulation (MDS) of Fel d 1 was performed with seven reported semiochemicals to evaluate the Fel d 1-ligand complex stability and decipher the semiochemical effect on Fel d 1 conformational epitopes. Fel d 1-lauric acid, Fel d 1-oleic acid, and Fel d 1-progesterone showed more stability and less fluctuation than other compounds. Fel d 1-linoleic acid and Fel d 1-pregnenolone displayed the most unstable complex with fluctuations. The effects of conformational changes on epitopes are discussed. All the ligand complexes drive substantial fluctuation towards the functionally exposed IgE-binding epitopes. Fel d 1 could be examined for its ligand-binding and conformational changes caused by mutations of B-cell epitopes.

Synergistic effect of conformational changes in phosphoglycerate kinase 1 product release

In the glycolysis pathway, phosphoglycerate kinase 1 (PGK1) transfers one phosphoryl-group from 1,3-diphosphoglycerate (1,3BPG) to ADP to product 3-phosphoglycerate (3PG) and ATP. The catalytic process is accompanied with the conversion between the open conformation and the closed conformation of PGK1. However, the dynamic collaboration mechanism between the PGK1 conformation transition and the products releasing process remains poorly understood. Here using molecular dynamics simulations combined with molecular mechanics generalized born surface area (MM/GBSA) analysis, we demonstrated that PGK1 in the closed conformation first releases the product ATP to reach a semi-open conformation, and releases the product 3PG to achieve the full open conformation, which could accept new substrates ADP and 1,3BPG for the next cycle. It is noteworthy that the phosphorylation of PGK1 at T243 causes the loop region (residues L248-E260) flip outside the protein, and the phosphorylation of Y324 leads PGK1 become looser. Both modifications cause the exposure of the ADP/ATP binding site, which was beneficial for the substrates/products binding/releasing of PGK1. In addition, the other post translational modifications (PTMs) were also able to regulate the ligands binding/releasing with different effects. Our results revealed the dynamic cooperative molecular mechanism of PGK1 conformational transition with products releasing, as well as the influence of PTMs, which would contribute to the understanding of PGK1 substrates/products conversion process and the development of small molecule drugs targeting PGK1. Communicated by Ramaswamy H. Sarma.

Osteogenic Differentiation Factors of Multipotent Mesenchymal Stromal Cells in the Current Understanding.

Molecular genetic mechanisms, signaling pathways, conditions, factors, and markers of the osteogenic differentiation of mesenchymal stem cells (MSCs) are being actively studied and are among the most studied areas in the field of cellular technology. This attention is largely due to the mounting contradictions in the seemingly classical knowledge and the constant updating of results in the analyzed areas. In this regard, we focus on the main classical concepts and some new factors and mechanisms that have a noticeable regulatory effect on the differentiation potential of postnatal MSCs. This review considers the importance of the sources of MSCs for the realization of their differentiation potential, molecular genetic factors and signaling pathways of MSC differentiation, the role of inflammatory cytokines and chemokines in osteogenesis, biomechanical signals, and the effect of conformational changes in the cellular cytoskeleton on MSC differentiation. It is concluded that it is necessary to move from studies focused on the effects of local genes to those taking multiple measurements of the gene-regulatory profile and the biomolecules critical for the implementation of numerous, incompletely studied osteogenic factors of endogenous and exogenous origin. Among the cornerstones of future (epi)genetic studies, whether osteomodulatory effects are realized through specific signaling pathways and/or whether cross-signaling with known genes drives the osteogenic differentiation of MSCs remains to be determined.

Catalytic Mechanism of Human Ten-Eleven Translocation-2 (TET2) Enzyme: Effects of Conformational Changes, Electric Field, and Mutations

Ten-eleven translocation (TET) family of enzymes are non-heme Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenases that perform oxidation of the methyl group of the 5-methylcytosine (5mC) on DNA. ...

Kinase inhibitors allosterically disrupt a regulatory interaction to enhance PKCα membrane translocation

The eukaryotic kinase domain has multiple intrinsically disordered regions whose conformation dictates kinase activity. Small molecule kinase inhibitors (SMKIs) rely on disrupting the active conformations of these disordered regions to inactivate the kinase. While SMKIs are selected for their ability to cause this disruption, the allosteric effects of conformational changes in disordered regions is limited by a lack of dynamic information provided by traditional structural techniques. In this study, we integrated multiscale molecular dynamics simulations with FRET sensors to characterize a novel allosteric mechanism that is selectively triggered by SMKI binding to the protein kinase Cα domain. The indole maleimide inhibitors BimI and sotrastaurin were found to displace the Gly-rich loop (G-loop) that normally shields the ATP-binding site. Displacement of the G-loop interferes with a newly identified, structurally conserved binding pocket for the C1a domain on the N lobe of the kinase domain. This binding pocket, in conjunction with the N-terminal regulatory sequence, masks a diacylglycerol (DAG) binding site on the C1a domain. SMKI-mediated displacement of the G-loop released C1a and exposed the DAG binding site, enhancing protein kinase Cα translocation both to synthetic lipid bilayers and to live cell membranes in the presence of DAG. Inhibitor chemotype determined the extent of the observed allosteric effects on the kinase domain and correlated with the extent of membrane recruitment. Our findings demonstrate the allosteric effects of SMKIs beyond the confines of kinase catalytic conformation and provide an integrated computational-experimental paradigm to investigate parallel mechanisms in other kinases.

Machine Learned Model for Solid Form Volume Estimation Based on Packing-Accessible Surface and Molecular Topological Fragments.

We present a machine learned model for predicting the volume of a homomolecular crystal based on the single-molecule structure, implemented in the open-source Python package for Molecular Volume Estimation (PyMoVE). The model is based on two descriptors: the volume enclosed by the packing-accessible surface and molecular topological fragments. To calculate the volume enclosed by the molecular surface, we have developed a new "projected marching cubes" algorithm. The new algorithm achieves a higher accuracy with a smaller number of elements than the traditional marching cubes algorithm, the marching tetrahedron variant, and Monte Carlo methods. The packing-accessible surface is then calculated using an optimized probe radius. The molecular topological fragments are used to construct a representation that captures the bonding environments of the atoms in the molecule. Feature selection is used to determine which fragments to include in the model. The accuracy and robustness of the model may be attributed to including both geometric and chemical features. The volume enclosed by the packing-accessible surface accounts for the presence of voids and sterically hindered regions as well as for the effect of conformational changes. The molecular topological fragments account for the effect of intermolecular interactions on the packing density. The model is trained on a dataset of structures extracted from the Cambridge Structural Database. Excellent performance is demonstrated for three validation sets of unseen data.

Exploring the State of the F1-ATPase after ATP Binding and before ADP Release: Effects of Conformational Changes on Phosphate Displacement

Single-molecule imaging experiments provide information that is not available from ensemble experiments. We are interested in the interpretation of dynamical studies imaging and manipulation in F₁-ATPase single-molecules. One key question that has arisen in single molecule stalling experiments is the erratic behavior a rotor angle of 55° between the binding and hydrolysis dwell angles of 0 and 80°, respectively. In our previous theoretical work, we used the elastic property of the rotor-stator structure to treat the experiments on controlled rotation. Our modeling suggests that there has to be a change in the bonding network, for example, of hydrogen bonds, as the system transitions between the two dwell points, perhaps at 55°, as indicated by an unusual stalling behavior around that angle. Therefore, in order to get further insights on these events, we have performed full-atomistic molecular dynamics (MD) simulations on the F₁-ATPase to explore the relationship between the conformational changes and the phosphate displacement. The pK_a values for phosphoric acid are 2.2, 7.2, and 12.3; although the effective pK_a for H₂PO₄⁻ within the binding site could be different. Hence, both protonation states (i.e., H₂PO₄⁻ and HPO₄²⁻) were assessed, performing molecular dynamics for 650 ns at 298.15K (Nose-Hoover thermostat) using the CHARMM36 force field. After the analysis of five MD trajectories, we found that the displacement of the phosphate was, to some extent, correlated with the dynamics of the protein. Moreover, one of the MD trajectories led to the complete release of the diprotic phosphate.

Near-infrared resonance stimulated Raman study of short-lived transients in PTB7 films

Low-bandgap conjugated polymers, which have an alternating structure of electron-donating and electron-withdrawing monomer units in their main chains, are expected to show high photovoltaic efficiency when the monomer units are appropriately designed. For understanding key factors of the photovoltaic efficiency, we have investigated the structure and dynamics of short-lived transients in films of a low-bandgap conjugated polymer with an alternating structure of thieno[3,4-b]thiophene and benzo[1,2-b:4,5-b′]dithiophene, PTB7, by time-resolved near-infrared stimulated Raman spectroscopy as well as time-resolved near-infrared absorption spectroscopy. Positive polarons of PTB7 are clearly distinguished from its singlet excitons in stimulated Raman spectra by the peak position of a CC stretch band of the thiophene rings in benzodithiophene and intensity of a CSC deformation band of them. These differences strongly suggest that the repeated structure of thiophene rings in the main chain predominantly contributes to the charge transfer characteristics of PTB7 in films. Time-resolved absorption and stimulated Raman spectra of PTB7 films blended with a fullerene derivative show that spectral changes associated with the initial charge separation complete within 1 ps while effects of conformational changes and intermediate species are absent. We suggest that alternating copolymers composed of electron-donating and electron-accepting units commonly undergo the initial charge separation process without conformational changes or intermediates.

Hybrid Electron Microscopy Normal Mode Analysis with Scipion.

Hybrid Electron Microscopy Normal Mode Analysis (HEMNMA) method was introduced in 2014. HEMNMA computes normal modes of a reference model (an atomic structure or an electron microscopy map) of a molecular complex and uses this model and its normal modes to analyze single-particle images of the complex to obtain information on its continuous conformational changes, by determining the full distribution of conformational variability from the images. An advantage of HEMNMA is a simultaneous determination of all parameters of each image (particle conformation, orientation, and shift) through their iterative optimization, which allows applications of HEMNMA even when the effects of conformational changes dominate those of orientational changes. HEMNMA was first implemented in Xmipp and was using MATLAB for statistical analysis of obtained conformational distributions and for fitting of underlying trajectories of conformational changes. A HEMNMA implementation independent of MATLAB is now available as part of a plugin of Scipion V2.0 (http://scipion.i2pc.es). This plugin, named ContinuousFlex, can be installed by following the instructions at https://pypi.org/project/scipion-em-continuousflex. In this article, we present this new HEMNMA software, which is user-friendly, totally free, and open-source. STATEMENT FOR A BROADER AUDIENCE: This article presents Hybrid Electron Microscopy Normal Mode Analysis (HEMNMA) software that allows analyzing single-particle images of a complex to obtain information on continuous conformational changes of the complex, by determining the full distribution of conformational variability from the images. The HEMNMA software is user-friendly, totally free, open-source, and available as part of ContinuousFlex plugin (https://pypi.org/project/scipion-em-continuousflex) of Scipion V2.0 (http://scipion.i2pc.es).

Substituent effects on the aromaticity of benzene—An approach based on interaction coordinates

Benzene and 23 monosubstituted and 32 disubstituted derivatives of benzene were optimized for minimum energy structures using the B3LYP/cc-pVTZ method. The force fields of all the compounds were evaluated at their optimized geometries using the same method and basis set. In order to understand the effect of substitution(s) on the aromaticity of benzene, the aromaticity index based on interaction coordinates (AIBIC) values were computed for each and the change from the benzene value was obtained. This difference, the substituent effect based on interaction coordinates (SEBIC), quantifies the effect of the substituent on the aromaticity of benzene ring satisfactorily. It is found that the AIBIC of disubstituted benzenes (XC6H4Y) could be predicted well by adding the respective SEBIC(C6H5X) and SEBIC(C6H5Y) values to the AIBIC of benzene. The projected force fields of the meta and para fragments of the monosubstituted benzenes when chosen properly contain the information about the directing influence of the substituent in terms of the electron density based on interaction coordinates (EDBIC). When the EDBIC(para) > EDBIC(meta) relative to benzene, the substituent is ortho-para directing, while when the reverse is true, it is meta directing. The effect of conformational changes on aromaticity has been studied using aminophenols and dihydroxybenzenes. The additivity rule and the EDBIC concept work adequately well in that the methods can have several useful practical applications that will benefit various areas of science. A good understanding of the substituent effects and the ability to predict them should add a new dimension to the applications of AIBIC.

Using Synthetic Peptides for Exploring Protein-Protein Interactions in the Assembly of the NADPH Oxidase Complex.

The NADPH oxidase complex, responsible for reactive oxygen species (ROS) generation by phagocytes, consists of a membrane-associated flavocytochrome b 558 (a heterodimer of NOX2 and p22phox) and the cytosolic components p47phox, p67phox, Rac(1 or 2), and p40phox. NOX2 carries all redox stations through which electrons flow from NADPH to molecular oxygen, to generate the primary ROS, superoxide. For the electron flow to start, a conformational change in NOX2 is required. The dominant hypothesis is that this change is the result of the interaction of NOX2 with one or more of the cytosolic components (NADPH oxidase assembly). At the most basic level, assembly is the sum of several protein-protein interactions among oxidase components. This chapter describes a reductionist approach to the identification of regions in oxidase components involved in assembly. This approach consists of "transforming" one component in an array of overlapping synthetic peptides and assessing binding to the peptides of another component, represented by a recombinant protein. The peptides are tagged with biotin, at the N- or C-terminus, and immobilized on streptavidin-coated 96-well plates. The protein partners are expressed with a 6His tag and added to the plates in the fluid phase. Binding of the protein to the peptides is quantified by a kinetic ELISA , using a peroxidase-conjugated anti-polyhistidine antibody. Protein-peptide binding assays were applied successfully to (a) identifying the binding site on one component (represented by peptides) for another component (proteins), (b) precisely defining the "binding sequence," (c) acquiring information on the binding site in the partner protein, (d) investigating the effect of conformational changes in proteins on binding to peptides, (e) determining the effect of physicochemical modification of peptides on binding of proteins, and (f) identifying epitopes recognized by anti-oxidase component antibodies by binding of antibody to peptide arrays derived from the component.

Effects of Conformational Changes in Peptide-CRM197 Conjugate Vaccines.

Conjugate vaccines prepared with the cross-reactive material 197 (CRM197) carrier protein have been successful in the clinic and are of great interest in the field of immunotherapy. One route to preparing peptide-CRM197 conjugate vaccines involves an activation-conjugation strategy, effectively coupling lysine residues on the protein to cysteine thiolate groups on the peptide of interest using a heterobifunctional linker as an activation agent. This method has been found to result in two distinct populations of conjugates, believed to be the result of a conformational change of CRM197 during preparation. This report explores the factors that lead to this conformational change, pointing to a model in which the unintentional alkylation of histidine-21 by the activating agent promotes the "opening" of the monomeric protein. This exposes a new set of lysine residues that are modified by additional activation agents. Subsequent peptide ligation to these sites results in the two conformers. This is the first time that a specific chemical modification is demonstrated to induce a defined conformational change for this carrier protein. Importantly, alternative conditions and reagents have been found to minimize this effect, improving the conformational homogeneity of peptide-CRM197 conjugates.

Length–dependence of conductance in benzothiadiazole molecular wires between graphene nanoribbon electrodes: Effect of conformational changes

In this research, we investigated the electronic transport mechanism of benzothiadiazole molecular wires connected to zigzag graphene nanoribbon (zGNR) electrodes on the basis of non-equilibrium Green's functions (NEGF) and density functional theory (DFT). It is obtained that the dynamical rotation of the central molecular wire affects the conjugated electron network along the transport direction and creates two different electronic devices with different electronic properties. First, the planer geometry, (zGNR|(IBT)n|zGNR), with strong coupling of molecular wire and graphene leads which have shown the molecular orbital delocalization over transmission eigenchannels inducing the current transport in such connections. Conformational change of connections is obtained by rotating the central molecular wire with respect to the transport direction creates the second class of electronic devices with low conductance values, (zGNR|(OBT)n|zGNR). The conductance decay constant indicates that non-resonant tunneling dominates the charge transport mechanism in the zGNR|(OBT)n|zGNR, while the zGNR|(IBT)n|zGNR devices have shown lower current attenuation that leads to a much lower decay factor and more conductive nano-connections for longer length of molecular bridge.

The Effect of Organophosphate (OP)‐Induced Structural Changes in Acetylcholinesterase on Kinetics of OP Inhibition and Oxime Reactivation

Organophosphate (OP) pesticides and nerve warfare agents covalently inhibit human acetylcholinesterase (hAChE) compromising cholinergic neurotransmission that can lead to fatal outcome. Effective therapy of OP intoxication requires that both, excess OP is removed from circulation and that activity of OP inhibited tissue hAChE is recovered. For both reactions nucleophilic oxime reactivation can play an essential role. For oxime assisted OP bioscavenging it is also important that the rate of inhibition of bioscavenger AChE is not compromised. Recently determined structures of diethylphosphorylated hAChE (POX‐hAChE) formed by paraoxon (POX) inhibition, both our unpublished and PDB released (5HF5 and 5HF8) show significant structural changes of the acyl pocket, immediately close to the active Ser203 when compared to the non‐inhibited enzyme. Those are likely to compromise nucleophilic oxime attack and rate of reactivation, but could also influence rate of hAChE inhibition by POX. Inhibition of AChE by dimethylphosphate analogue of POX (dmPOX) does not lead to conformational changes in the conjugated AChE (dmPOX‐AChE). In order to investigate effect of conformational changes in POX‐hAChE on rates of POX inhibition and oxime reactivation we studied dependence of rates of those reactions on reaction temperatures compared to dmPOX reactions. No difference was observed in temperature dependences of inhibition by diethyl‐ and dimethylphosphates. However, we observed strong temperature dependence of the oxime 2PAM reactivation, where reactivation of POX‐hAChE at 37 °C appeared an order of magnitude faster than the reaction at 22 °C. Reactivation of dimethylphosphorylated hAChE (dmPOX‐hAChE), as well as both dimetyhyl‐ and diethyl‐ phosphorylated Y337A/F338A hAChE mutant by 2PAM was significantly less temperature dependent, consistent with the absence of compromising conformational changes in dmPOX‐hAChE and in the mutant. This result indicates that formation of distorted acyl pocket loop in POX‐hAChE is not limiting for inhibition reaction but affects rates of oxime reactivation. Ability of POX‐hAChE to change acyl pocket loop conformation at the higher temperature allows for faster oxime reactivation and emphasizes the importance of conformational flexibility of hAChE for the efficient oxime reactivation.Support or Funding InformationThis work was supported by the CounterACT Program, National Institutes of Health Office of the Director, Grant 1U01NS083451 from NINDS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

First hyperpolarizability of isomers of pyridinium N-phenoxide betaine dye in solution using the ASEC-FEG method

The linear and nonlinear properties of isomeric forms of pyridinium-N-phenoxide betaine dye were investigated in protic and aprotic solvents using atomistic simulations. We employed the sequential Quantum Mechanics/Molecular Mechanics (S-QM/MM) and the free energy gradient (FEG) methods to optimize the geometry of each isomer in chloroform, acetonitrile, methanol and water. The results show a complex dependence of the first hyperpolarizability with respect to the solvent nature and isomeric form, with a marked effect of conformational changes for para-betaine. Large contrasts of the first hyperpolarizability show a clear distinction between isomeric forms in solution that could be experimentally detected.

Hexadecaphyrin-(1.0.0.0.1.1.0.1.1.0.0.0.1.1.0.1): A Dual Site Ligand That Supports Thermal Conformational Changes.

A new expanded porphyrin, hexadecaphyrin-(1.0.0.0.1.1.0.1.1.0.0.0.1.1.0.1), is reported. It was obtained via the condensation of a hexapyrrolic derivative prepared in turn from a bipyrrole dialdehyde and a stable quaterpyrrole precursor. This hexadecaphyrin contains eight direct α-pyrrole-to-α-pyrrole linkages in its structure. It supports the formation of bimetallic complexes of both zinc and cobalt that are characterized by different conformational structures. Furthermore, a mixed zinc/cobalt macrocycle has been prepared. The cobalt bimetallic complex shows two stable conformations with the same oxidation state that are in equilibrium. All compounds have been characterized by common spectroscopic means, and single crystal X-ray diffraction structures were obtained for all macrocyclic compounds. DFT calculations and transient absorption spectra were used to study the electronic features of the complexes and the effect of conformational changes. This system shows promise as an accumulated heat sensor.

Theoretical analysis of tautomerization of succinimide and analogous compounds: insights from DFT approach

Tautomerizations of biologically and medicinally important heterocyclic compound, 2,5-pyrrolidinedione, commonly known as succinimide and two of its analogous compounds, 2,4-pyrrolidinedione and 3,4-pyrrolidinedione have been investigated at the density functional theory (DFT)/M06-2X level in aqueous medium, implementing polarizable continuum model (PCM). We have extended our investigation of tautomerism to the sulfur analogues of the aforementioned compounds also, i.e., 2,5-pyrrolidinedithione, 2,4-pyrrolidinedithione, and 3,4-pyrrolidinedithione. Tautomerism observed in these compounds are mainly keto-enol, thio-thiol and amine-imine, but we have detected two new kind of tautomerization shown by some of the abovementioned compounds, named as keto-epoxy (for the oxygen analogue) and thio-thioepoxy (for the sulfur analogue) which have not yet been reported in the literature. Relative energies (Er) and activation energies (Ea) have been calculated for all the tautomers and tautomerization processes. The potential energy surfaces (PESs) have been constructed using the M06-2X energy values. It has been observed that the energy difference found in the tautomers of sulfur analogues is relatively lower than that of the corresponding oxygen analogues, so does the activation energy barrier. As one-electron redox properties play an important role in biological systems, we have also explored the effect of conformational changes on the overall redox properties of the said compounds by calculating the adiabatic and vertical ionization potentials (AIPs and VIPs, respectively) and adiabatic electron affinities (AEAs).