Solution conformational preferences of glutaric, 3‐hydroxyglutaric, 3‐methylglutaric acid,and their mono‐ and dianions

Conformational preferences of glutaric, 3‐hydroxyglutaric and 3‐methylglutaric acid, and their mono‐ and dianions have been investigated with the aid of NMR spectroscopy. In contrast to succinic acid, glutaric acid displays essentially statistical conformational equilibria in polar and non‐polar solutions of high and low hydrogen‐bonding ability with no clear evidence for intramolecular hydrogen‐bonding interactions. The acid ionization constant ratios, K ₁/K₂, in D₂O and DMSO of glutaric, 3‐hydroxyglutaric, and 3‐methylglutaric acids also indicate that intramolecular interactions are much less important than, or indeed insignificant, for shorter‐chain acids. FTIR studies on 3‐methylglutaric acid indicate some preference for either association with solvent or dimerization, depending on the solvent, rather than intramolecular hydrogen bonding. Copyright © 2008 John Wiley & Sons, Ltd.     

A detailed DFT/TDDFT study on excited‐state intramolecular hydrogen bonding dynamics and proton‐transfer mechanism of 2‐phenanthro[9,10‐d]oxazol‐2‐yl‐phenol

In this present work, using density functional theory and time‐dependent density functional theory methods, we theoretically study the excited‐state hydrogen bonding dynamics and the excited state intramolecular proton transfer mechanism of a new 2‐phenanthro[9,10‐d]oxazol‐2‐yl‐phenol (2PYP) system. Via exploring the reduced density gradient versus sign(λ₂(r))ρ(r), we affirm that the intramolecular hydrogen bond O1‐H2?N3 is formed in the ground state. Based on photoexcitation, comparing bond lengths, bond angles, and infrared vibrational spectra involved in hydrogen bond, we confirm that the hydrogen bond O1‐H2?N3 of 2PYP should be strengthened in the S₁ state. Analyses about frontier molecular orbitals prove that charge redistribution of 2PYP facilitates excited state intramolecular proton transfer process. Via constructing potential energy curves and searching transition state structure, we clarify the excited state intramolecular proton transfer mechanism of 2PYP in detail, which may make contributions for the applications of such kinds of system in future.     

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

A series of trans‐2‐aminocyclohexanol derivatives have been explored as powerful conformational pH triggers. On protonation of the amino group, a conformer with equatorial position of ammonio and hydroxy groups becomes predominant because of an intramolecular hydrogen bond and electrostatic interactions. The energy of these interactions was estimated to be above 10 kJ/mol and in some models exceeded 20 kJ/mol (strong enough to twist a ring in tert‐butyl derivatives). As a result of this conformational flip, all other substituents are forced to change their orientation. If the substituents are designed to perform certain geometry‐dependent functions, for example, as cation chelators or as lipid tails, such acid‐induced transition may be used to control the corresponding molecular properties. The pH sensitivity of conformational equilibria was explored by ¹H nuclear magnetic resonance spectroscopy (NMR), and the titration curves were used for estimation of the pK_a values of protonated compounds that varied from 2.6 to 8.5 (in d₄‐methanol) depending on the structure of amino group. Thus, trans‐2‐aminocyclohexanols can be also used as conformational pH indicators in organic solvents.     

A theoretical and experimental 1H NMR spectroscopy study of the stereoelectronic interactions that rule the conformational energies of alanine and valine methyl ester

Amino acids exhibit a bipolar zwitterionic structure (⁺H₃N‐CHR‐COO^?) in solution; hence, conformational studies of these compounds have been limited to the gas phase. The conformational preferences of amino acids have been widely attributed to intramolecular hydrogen bonding, despite steric and hyperconjugative effects. In this work, we propose the conformational study of alanine and valine methyl esters, which do not show zwitterionic structures in solution, by¹H NMR and theoretical calculations. The ³J_HH spin–spin coupling constants and theoretical calculations were found to be in agreement, showing that the interplay between steric hindrance and hyperconjugation is the forces that are responsible for determining the conformational preferences of alanine and valine methyl esters. Copyright © 2013 John Wiley & Sons, Ltd.     

Theoretical and Experimental Study of the Conformation and Vibrational Frequencies of N‐Acetyl‐L‐alanine and N‐Acetyl‐L‐alaninate

The vibrational frequencies of N‐acetyl‐L‐alanine (NAAL), its potassium salt (NAALK) and its free anionic form (NAAL^?) are calculated using density functional theory (B3LYP) combined with the 6‐311 + + G(d,p) basis set. The experimental Raman spectrum of solid NAALK and the scaling factors for calculated values are discussed as well. The three species are characterized by intramolecular NH…O hydrogen bonds leading to the formation of a five‐membered ring. As indicated by the intramolecular (N)H…O distances and by the ν(NH) frequencies, the strength of the intramolecular hydrogen bond is ordered as follows: NAAL^? < NAALK < NAAL^?. Owing to their difference in the coupling with other vibrational modes, the in‐plane and out‐of‐plane vibrations do not reflect the strength of the hydrogen bond.     

A theoretical study on the ESPT mechanism for a novel Bis‐HPBT fluorophore

In this work, based on the density functional theory and time‐dependent density functional theory methods, the properties of the 2 intramolecular hydrogen bonds (O1‐H2···N3 and O4‐H5···N6) of a new photochemical sensor 4‐(3‐(benzo[d]thiazol‐2‐yl)‐5‐tert‐butyl‐4‐hydroxybenzyl)‐2‐(benzo[d]thiazol‐2‐yl)‐6‐tert‐butyl phenol (Bis‐HPBT) have been investigated in detail. The calculated dominating bond lengths and bond angles about these 2 hydrogen bonds (O1‐H2···N3 and O4‐H5···N6) demonstrate that the intramolecular hydrogen bonds should be strengthened in the S₁ state. In addition, the variations of hydrogen bonds of Bis‐HPBT have been also testified based on infrared vibrational spectra. Our theoretical results reproduced absorption and emission spectra of the experiment, which verifies that the theoretical level we used is reasonable and effective in this work. Further, hydrogen bonding strengthening manifests the tendency of excited state intramolecular proton transfer (ESIPT) process. Frontier molecular orbitals depict the nature of electronically excited state and support the ESIPT reaction. According to the calculated results of potential energy curves along stepwise and synergetic O1‐H2 and O4‐H5 coordinates, the potential energy barrier of approximately 1.399 kcal/mol is discovered in the S₁ state, which supports the single ESIPT process along with 1 hydrogen bond of Bis‐HPBT. In other words, the proton transfer reaction can be facilitated based on the electronic excitation effectively. In turn, through the process of radiative transition, the proton‐transfer Bis‐HPBT‐SPT form regresses to the ground state with the fluorescence of 539 nm.     

Rotational spectra, conformational structures, and dipole moments of thiodiglycol by jet-cooled FTMW and ab initio calculations

The rotational spectra of three low-energy conformers of thiodiglycol (TDG) (HOCH₂CH₂SCH₂CH₂OH) have been measured in a molecular beam using a pulsed-nozzle Fourier-transform microwave spectrometer. To determine the likely conformational structures with ab initio approach, conformational structures of 2-(ethylthio)ethanol (HOEES) (CH₃CH₂SCH₂CH₂OH) were used as starting points together with the consideration of possible intramolecular hydrogen bonding in TDG. Three lower-energy conformers have been found for TDG at the MP2=Full/6311G** level and ab initio results agree nicely with experimentally determined rotational constants. In addition, Stark measurements were performed for two of the three conformers for dipole moment determinations, adding to our confidence of the conformational structure matches between experimental observations and ab initio calculations. Of the three lower-energy conformers, one displays a compact folded-like structure with strong hydrogen bonding between the two hydroxyl groups and the central sulfide atom. Two other conformers have relatively open chain-like structures with hydrogen bonding between each of the hydroxyl groups to the central sulfur atom, of which one has pure b-type dipole moment according to the ab initio results.     

Theoretical insight into the excited‐state behavior of a novel Compound 1: A TDDFT investigation

In the present work, using density functional theory and time‐dependent density functional theory methods, we investigated and presented the excited‐state intramolecular proton transfer (ESIPT) mechanisms of a novel Compound 1 theoretically. Analyses of electrostatic potential surfaces and reduced density gradient (RDG) versus sign(λ₂)ρ, we confirm the existence of intramolecular hydrogen bond O1‐H2···N3 for Compound 1 in the S₀ state. Comparing the primary structural variations of Compound 1 involved in the intramolecular hydrogen bond, we find that O1‐H2···N3 should be strengthened in the S₁ state, which may facilitate the ESIPT process. Concomitantly, infrared (IR) vibrational spectra analyses further verify the stability of hydrogen bond. In addition, the role of charge transfer interaction has been addressed under the frontier molecular orbitals, which depicts the nature of electronical excited state and supports the ESIPT reaction. The theoretically scanned and optimized potential energy curves according to variational O1‐H2 coordinate demonstrate that the proton transfer process should occur spontaneously in the S₁ state. It further explains why the emission peak of Compound 1‐enol was not reported in previous experiment. This work not only presents the ESIPT mechanism of Compound 1 but also promotes the understanding of this kind of molecules for further applications in future.     

Difference between 1H NMR signals of primary amide protons as a simple spectral index of the amide intramolecular hydrogen bond strength

The effect of the intramolecular H‐bonding of the primary amide group on the spectral properties and reactivity of this group towards electrophiles has been studied in systematic rows of 1,2,5,6,7,8‐hexahydro‐7,7‐dimethyl‐2,5‐dioxo‐1‐R‐quinoline‐3‐carboxamides and 2‐aryliminocoumarin‐3‐carboxamides using ¹H and ¹⁵N NMR spectroscopy and the kinetics of model reactions. The upfield signal of the amide proton that is not intramolecularly H‐bonded (H^a) depends on external factors such as solvent nature and concentration. At the same time, the downfield chemical shift of the H^b proton (bonded by the intramolecular hydrogen bond) depends mostly on the strength of the intramolecular H‐bond, which is affected by such internal factor as electron nature of substituent R. The substituent's influence on the H^b proton's chemical shift is more effective in deuterochloroform medium than in DMSO‐d₆ where the intramolecular hydrogen bond is less stable. The value Δδ(H) = δ(H^b) ? δ(H^a) is suggested as a simple comparative spectral index of the intramolecular hydrogen bond strength in these and similar compounds. By contrast, the effect of R on the ¹⁵N NMR chemical shift of the amide nitrogen has turned out to be too small to estimate changes of the electron density at the nitrogen. The effect of the intramolecular H‐bond on the reactivity of the amide group is twofold. When the cleavage of the H‐bond occurs on the rate limiting step it dramatically reduces the reaction rate. In the other case, the strengthening of the H‐bond favors the reaction rate because of the increase of the electron density at the amide nitrogen. Copyright © 2011 John Wiley & Sons, Ltd.     

Effect of proton donors on the intramolecular coordination C=O→Si–F in (acyloxymethyl)trifluorosilanes. Ab initio,DFT and FTIR study,QTAIM analysis

The intramolecular С=O→Si coordination in H‐complexes of (acetoxymethyl)trifluorosilane and (benzoyloxymethyl)trifluorosilane with proton donors HCl, PhOH, MeOH, and CHCl₃ was investigated by density functional theory and second‐order Møller‐Plesset perturbation theory (MP2) methods. Interrelation and mutual influence of the intramolecular coordination bond С=O→Si and intermolecular hydrogen bonds C=O···H and Si–F···H in H‐complexes was established using the AIM and NBO analyses. The С=O→Si coordination is weakened by the C=O···H hydrogen bonding but enhanced by the Si–F_ax···H hydrogen bonding. The structure of H‐complexes of (acetoxymethyl)trifluorosilane with proton donors in solution was determined by comparing the ν(C=O) and ν(Si–F) frequencies calculated using the conductor‐like polarizable continuum model and their experimental Fourier transform infrared values. Copyright © 2014 John Wiley & Sons, Ltd.     

Influence of the hydrogen bonding on the basicity of selected macrocyclic amines

The optimized minimum‐energy geometries of different macrocyclic amines and their protonated structures were determined by using ab initio and density functional theory (DFT) calculations. All the gas phase optimizations and energy calculations were performed at the DFT/B3LYP/6‐311++G(d,p) level of theory. The HF/6‐31 + G(d,p) level was used for all single point calculations in the solution phase. Geometry optimizations indicate that the most stable structures are stabilized by intramolecular hydrogen bonds. The proton affinity (PA) of macrocyclic amines is controlled by the strength of intramolecular hydrogen bonds of macrocyclic amines. These hydrogen bonds strongly influence the basicity of heteroatoms in macrocycles. The highest PA value among the studied macrocyclic amines was found to be 264.9 kcal mol^?1 for structure 7. This is comparable with PA of proton sponges such as 1,8‐bis(dimethylamino)naphthalene. The solution phase calculations were carried out in the dimethyl sulfoxide solution as a commonly used solvent in organic reactions. Natural bond orbital analysis was performed to calculate the charge transfers and the second‐order interaction energies (E⁽²⁾) between the donor and acceptor. Quantum theory of atoms in molecules (QTAIM) was also applied to determine the nature of hydrogen bonds. QTAIM studies showed that the intramolecular hydrogen bonds in these structures are electrostatic (closed‐shell) interactions as well as partially covalent and partially electrostatic in nature. Copyright © 2012 John Wiley & Sons, Ltd.     

Raman,FT‐IR,and DFT studies of 3,5‐pyrazoledicarboxylic acid and its Ce(III) and Nd(III) complexes

3,5‐Pyrazoledicarboxylic acid was used as a ligand for the synthesis of its Ce(III) and Nd(III) complexes. The complexes of Ce(III) and Nd(III) with 3,5‐pyrazoledicarboxylic acid were synthesized and their compositions were determined by elemental analysis. Vibrational study in the solid state of 3,5‐pyrazoledicarboxylic acid and its new Ce(III) and Nd(III) complexes was performed by IR and Raman spectroscopy. The changes observed between the IR and Raman spectra of the ligand and of the complexes allowed us to establish the coordination mode of the metal in both complexes. The comparative vibrational analysis of the free ligand and its lanthanide(III) complexes gave evidence that 3,5‐pyrazoledicarboxylic acid binds Ln(III) through the deprotonated carboxylic oxygens. The density functional theory (DFT) calculated geometries, harmonic vibrational modes and Raman scattering activities of the ligand were in good agreement with the experimental data, and a complete vibrational assignment is being proposed. The experimental IR and Raman bands of the ligand were assigned to normal modes on the basis of DFT calculations. The effect of the intramolecular hydrogen bonds in the ligand on vibrational mode positions is also discussed. The characteristic IR and Raman bands of 3,5‐pyrazoledicarboxylic acid and its lanthanide complexes were specified and discussed. Copyright © 2006 John Wiley & Sons, Ltd.     

Tautomerism and Spectral Properties of 2‐Anilinomethylenecyclopentane‐1,3‐Dione According to the Data of Quantum‐Mechanical Calculations, IR Spectroscopy, and Secondary Isotopic Effects in the 13C NMR Spectra

Using the methods of IR spectroscopy, ¹³C NMR spectroscopy, and quantum‐mechanical methods (semiempirical AM1 and PM3 methods and the method of the density functional theory), we have investigated the tautomerism and spectral properties of 2‐anilinomethylenecyclopentane‐1,3‐dione. It is shown that this compound in crystals and solutions in CCl₄ and CHCl₃ exists in the form of a tautomer with an exocyclic arrangement of the C=C bond and a NH group participating in the formation of an intramolecular hydrogen bond with a carbonyl group of the carbocycle.     

Theoretical insight into the excited‐state proton transfer process: Role of the substituent ‐CN on HBT system

In this work, using density functional theory and time‐dependent density functional theory methods, we theoretically studied the excited‐state behaviors of 3 novel 2‐(2‐hydroxyphenyl)benzothiazole (HBT) derivatives (HBT‐H‐H, HBT‐CN‐H, and HBT‐CN‐CN). Analyses about primary chemical structures such as bond lengths and bond angles, we found that all the intramolecular hydrogen bonds in these 3 structures should be strengthened in the S₁ state upon the photoexcitation. Exploring the infrared vibrational spectra at the hydrogen bonds groups, we confirmed that nonsubstitutional HBT‐H‐H structure might play more important roles in the excited‐state intramolecular proton transfer (ESIPT) reaction than HBT‐CN‐H and HBT‐CN‐CN. Further, investigating vertical excitation process, it can be revealed that charge redistribution involved in hydrogen bonding moieties could facilitate the ESIPT reaction. Based on constructing potential energy curves of both S₀ and S₁ states, we confirmed that the substituents on HBT systems can reasonably regulate and control the ESIPT processes because of the different potential energy barriers. We deem that this present work not only elaborates the different excited‐state behaviors of HBT‐H‐H, HBT‐CN‐H, and HBT‐CN‐CN but also may play important roles in designing and developing new materials and applications involved in HBT systems in future.     

The role of water in the design of glycosidic linkage flexibility

In this paper we show how a variety of computational methods are used to understand the role that water plays in the solution conformational dynamics of carbohydrates. A comparison is made between maltose and a designed disaccharide (α-D-Glc-NAc-(1→4)-β-D-Glc-3-NH₂) in which the cross glycosidic linkage hydrogen bonds have been significantly strengthened. However, despite the stronger intramolecular hydrogen bonds in the maltose derivative, the correlation times for glycosidic dihedral angle fluctuations are approximately the same for the two sugars. Upon investigation of the water in the first hydration shells for the two disaccharides, high water probability densities were found between the functional groups straddling the glycosidic linkage that bonds the two monosaccharides together. This probability density corresponds to single water molecules forming bridging hydrogen bonds between the functional groups on either side of the linkage for periods of 3.66 ps in the case of maltose and 8.36 ps in the case of the amine derivative. Ab initio studies of saccharide structure interaction with single water molecules reveal that these intermolecular (sugar-solvent) hydrogen bonds are of similar strength to the intramolecular (sugar-sugar) hydrogen bonds. This combination of molecular dynamics and ab initio computational methods demonstrates that increasing the internal hydrogen bond strength in oligosaccharides does not lead to significantly slower internal molecular motion of these sugars in solution. The intermolecular hydrogen bonds formed with water compete equally with the intramolecular hydrogen bonds in the sugar. This result has important implications when considering hydrophobic versus hydrophilic effects in glycoproteins.     

Vibrational spectra and scaled quantum chemical studies of the structure of Martius yellow sodium salt monohydrate

The FT‐IR and Raman spectra of Martius Yellow sodium salt Monohydrate (MYM) [2, 4‐dinitro‐1‐naphthol sodium salt] in solid‐phase have been measured. The geometry, intramolecular hydrogen bonding and harmonic vibrational wavenumbers of MYM have been investigated with the help of B3LYP density functional theory (DFT) methods. The detailed interpretation of the vibrational spectra has been carried out with the aid of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMFF). The existence of intramolecular C H···O improper, blue‐shifted hydrogen bonding was investigated by means of the NBO analysis. The infrared and Raman spectra were predicted theoretically from the calculated intensities. The observed and the calculated spectra were found to be in good agreement. Copyright © 2009 John Wiley & Sons, Ltd.     

Density functional theoretical studies on photoswitching and charge migration dynamics of thio and selenoureidopeptides

Density functional theoretical calculations have been performed to investigate the changes in electronic structure at ground and excited states of ureidopeptides on substitution with higher chalcogens like sulphur and selenium for oxygen. This replacement results in a reduced preference towards the intramolecular hydrogen bonding interaction, thus linear conformers are found to be stable at both states. Nevertheless, conformational switching observed during this process is mainly due to n to π* transition that leads to the dihedral angle ω change from trans to cis with a rotational barrier of 10 to 17 kcal mol^‐1. The computed barrier is lesser than that reported for oxopeptides (20 kcal mol^‐1). And, the hole migration dynamics after immediate ionization illustrates that the hole originated at ureido end evolves in time (2?4 fs) while the hole generated at the carboxylate end will not evolve as reported for ureidopeptides. The usage of these candidates as photoswitches has also been explored.     

Preferential mode of cyclization of tetrahydrofuran amino acids containing peptides: some theoretical insights

Theoretical insights have been provided for the observed preference of cyclodimerization over intramolecular cyclization reactions in linear tripeptides containing “2,5‐cis” (2S,5R)‐tetrahydrofuran amino acid as well as in those containing “2,5‐trans” (2S,5S)‐tetrahydrofuran amino acid, using quantum chemical methods. The geometries of species involved as well as the feasibility of cyclization reactions are studied at the B3LYP/6‐31G(d,p) level of theory in gas phase as well as in solvent phase. Thermodynamic data from Hessian calculations favor the intermolecular cyclization. Analysis of optimized geometries reveals the existence of additional stabilizing hydrogen bonding interactions in intermolecularly cyclized products. The existence of these second‐order interactions is substantiated by topological (atoms in molecules (AIM)) and natural bond orbital (NBO) analyses. Such interactions are absent in the intramolecular cyclization products. Further justification for the presence of stabilizing interactions in intermolecularly cyclized products comes from the molecular electrostatic potentials and electron density surfaces. Kinetic control favoring the intermolecularly cyclized products due to additional entropy of activation in the intramolecular case is surmised. Copyright © 2009 John Wiley & Sons, Ltd.     

Intramolecular hydrogen bonding in chiral alcohols: The microwave spectrum of the chloropropanols

The microwave Fourier transform spectrum of a mixture of 1-chloropropan-2-ol and 2-chloropropan-1-ol has been recorded in the range 5-18 GHz. The spectrum is extremely dense, as a result of both the large number of species present in the supersonic expansion, and the splitting of rotational transitions due to quadrupole coupling. Two conformational isomers of each molecule have been identified, and both the ³⁵Cl and ³⁷Cl isotopomers have been observed for both conformations of 1-chloropropan-2-ol and the most abundant conformation of 2-chloropropan-1-ol. All four observed conformations have weak intramolecular hydrogen bonds between the hydroxyl hydrogen and the chlorine atom. The basis of our assignment is a series of ab initio calculations, performed using the GAUSSIAN package, good agreement being observed between theoretical and experimental values of the rotational constants. Analysis of isotopic substitution and quadrupole coupling effects has reinforced this assignment. First-order centrifugal distortion coefficients, as well as diagonal and (in some cases) off-diagonal quadrupole tensor components have also been extracted. Diagonalisation of the quadrupole tensors for the ³⁵Cl isotopomers results in a near-cylindrical quadrupole tensor, distorted in the C-Cl-H plane. This distortion, which is somewhat larger than in several comparable systems, supports the assertion that the most prevalent conformations are stabilised by an intramolecular hydrogen bond.     

A theoretical assignment on excited‐state intramolecular proton transfer mechanism for quercetin

In the present work, we investigate a new chromophore (ie, quercetin) (Simkovitch et al J Phys Chem B 119 [2015] 10244) about its complex excited‐state intramolecular proton transfer (ESIPT) process based on density functional theory and time‐dependent density functional theory methods. On the basis of the calculation of electron density ρ( r ) and Laplacian ?²ρ( r ) at the bond critical point using atoms‐in‐molecule theory, the intramolecular hydrogen bonds (O₁‐H₂?O₅ and O₃‐H₄?O₅) have been supported to be formed in the S₀ state. Comparing the prime structural variations of quercetin involved in its 2 intramolecular hydrogen bonds, we find that these 2 hydrogen bonds should be strengthened in the S₁ state, which is a fundamental precondition for facilitating the ESIPT process. Concomitantly, infrared vibrational spectra analysis further verifies this viewpoint. In good agreement with previous experimental spectra results, we find that quercetin reveals 2 kinds of excited‐state structures (quercetin* and quercetin‐PT1*) in the S₁ state. Frontier molecular orbitals depict the nature of electronically excited state and support the ESIPT reaction. Our scanned potential energy curves according to variational O₁‐H₂ and O₃‐H₄ coordinates demonstrate that the proton transfer process should be more likely to occur in the S₁ state via hydrogen bond wire O₁‐H₂?O₅ rather than O₃‐H₄?O₅ because of the lower potential energy barrier 2.3 kcal/mol. Our present work explains previous experimental result and makes up the deficiency of mechanism in previous experiment. In the end, we make a reasonable assignment for ESIPT process of quercetin.