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Using density functional theory, polyols were used as model ligands for Cu+/Cu2+ complexes to study the role of the hydrogen bond network on the metal binding affinity. In addition to the gas phase studies, the calculations were performed in 1‐decanol and DMSO solvents. The Cu2+ complexes were the most stable complexes with the highest bond dissociation energies (BDE). The presence of three H‐bonds in the first shell increased BDE values up to 17.99 and 57.07 kcal/mol for Cu+ and Cu2+ complexes in the gas phase, respectively, whereas the presence of another three H‐bonds in the second shell increased BDE values up to 7.27 and 24.35 kcal/mol for Cu+ and Cu2+ complexes in the gas phase, respectively. Therefore, this H‐bond network caused, for example, a more stable Cu+ complex with a formation constant of 1.4 × 1017 times. The natural bond orbital (NBO), atoms in molecules (AIM), and reduced density gradient (RDG) analyses showed that the intramolecular hydrogen bond network led to the enhancement of metal‐binding affinity. [ABSTRACT FROM AUTHOR]

In this work, the role of Lewis acid–base (LAB) interaction on the stereoselectivity of the Diels–Alder (DA) reaction has been studied by DFT in gas and solution (dichloromethane) phases. The calculations were performed at the B3LYP/6-311G++ (d, p) level. Two different series of DA reactions were investigated: (1)—three mono-substituted cyclopentadienes + dimethyl(vinyl)borane; (2)—five α,β-unsaturated carbonyl compounds + cyclopenta-2,4-dien-1-yldimethylborane. The reacting diene and dienophile pairs were chosen to restrict LAB interaction to the exo reaction pathway. It was found that in some of the examined cases, the favorable LAB interaction is so strong that it can lead to a completely exo-selective DA reaction. Furthermore, a novel multistep synthetic method was hypothesized for preparing exo cycloadduct with near 100% stereoselectivity. Our results can open up new avenues toward the rational design of exo-selective DA reactions for synthesizing novel bioorganic compounds. [ABSTRACT FROM AUTHOR]

Designing drug delivery systems for therapeutic compounds whose receptors are located in the cytosol of cells is challenging as a bilayer cell membrane is negatively charged. The newly designed drug delivery systems should assist the mentioned drugs in passing the membrane barriers and achieving their targets. This study concentrated on developing novel ionic liquids (ILs) that interact effectively with cell membranes. These ILs are based on glucose-containing choline and are expected to be non-toxic. The binding energies of the known pharmaceutically active ionic liquids were calculated at the B3LYP/6-311++G(d,p) level in the gas phase and compared with those of our newly designed carbohydrate-based ionic liquids. Subsequently, we employed MD simulations to obtain information about the interactions of these known and designed ILs with the cell membrane. In our approach, we adopted QM and MD studies and illustrated that there could be a link between the QM and MD results. [ABSTRACT FROM AUTHOR]

DNA polymerase η (polη) is of significant value for designing new families of anticancer drugs. This protein takes a role in many stages of the cell cycle, including DNA replication, translesion DNA synthesis, and the repairing process of DNA. According to many studies, a high level of expression of polη in most cases has been associated with low rates of patients' survival, regardless of considering the stage of tumor cells. Thus, the design of new drugs with fewer side effects to inhibit polη in cancerous cells has attracted attention in recent years. This project aims to design and explore the alternative inhibitors for polη, which are based on carbohydrates and amino acids. In terms of physicochemical properties, they are similar to the traditional anticancer drugs such as Cytarabine (cytosine arabinose). These alternative inhibitors are supposed to disrupt the DNA replication process in cancerous cells and prevent the tumor cells from mitosis. These newly designed structures, which are based on natural products, are expected to be non-toxic and to have the same chemotherapeutic impact as the traditional agents. The combinatorial use of quantum mechanics studies and molecular dynamic simulation has enabled us to precisely predict the inhibition mechanism of the newly designed structure, which is based on carbohydrates and amino acids, and compare it with that of the traditional chemotherapeutic drugs such as Cytarabine. Our results suggest that the inhibitors containing the natural building blocks of amino acid and carbohydrate could be considered alternative drugs for Cytarabine to block polη. [ABSTRACT FROM AUTHOR]

PIM-1 is a serine-threonine kinase mainly expressed in tissues like the Thymus, spleen, bone marrow, and liver. Overexpression of PIM kinases occurs in various types of human tumours, such as lymphomas, prostate cancer, and oral cancer. As a result, the design of drugs to inhibit PIM-1 in cancerous cells has attracted much attention in recent years. This study aimed to design the alternative inhibitors for PIM-1 kinase, which are based on carbohydrates and amino acids and are expected to be non-toxic with the same chemotherapeutic effects as the traditional known anticancer drugs. The combinatorial use of quantum mechanics (QM) and molecular dynamic simulation (MD) has enabled us to precisely predict the inhibition of PIM-1 kinase by the novel designed drugs and compare them with the recently synthesized chemotherapeutic drugs such as DBC (Table 1). All designed structures were optimized at the B3LYP/6-311++G(d,p) level. The designed structure UNK4 (Table 1) was the most similar structure to DBC in terms of volumes, areas, and electrostatic potential map to DBC. The results obtained in this research represented that UNK4, with the building blocks of amino acid and cyclic carbohydrates could be considered an alternative anticancer drug for DBC. [ABSTRACT FROM AUTHOR]

We have studied the intramolecular H‐bonds existing in cyclic and open forms of glucose using B3LYP/6‐311++G(d,p) level, AIM, and NBO methods. The theoretical results indicated that based on acidity values, (ΔHacid), glucose in the open form is more acidic than cyclic form. The acidity values for open and cyclic glucose (332 and 338 kcal/mol) exhibit significantly lower values (i.e., stronger acid) than the reported acidity values for α‐/ß‐anomers of D‐glucopyranose and simple alcohols. Because their conjugate bases are more stabilized through trifurcated and bifurcated intramolecular H‐bonds. AIM analysis showed normal H‐bonds in the conjugate bases of open glucose (O‐Glc), bifurcated, and normal H‐bonds in the conjugate base of cyclic glucose. In the conjugate base of glucose, the O–H···O bonds are categorized as mostly electrostatic and strong, whereas multiple interactions including C–H···O, C–H···H–C (dihydrogen bonding), C–H···C–H, and C=O···H are categorized as weak H‐bonds. The NBO results confirm that the O–H···O intramolecular H‐bonds should be the strongest among all H‐bonds existing within glucose. [ABSTRACT FROM AUTHOR]

Ionic liquids, which are widely known as room temperature molten salts, have been the subject of much scientific debate for more than a decade. These compounds can be used as green solvents or even as additives in many reactions. Due to their noticeable conductivity, which is a function of the interaction energies existing between the ion pairs in ionic liquids, the synthesis and introduction of new families of these chemicals are of importance. The target of this paper is to design new carboxylate-based ionic liquids containing OH and CF3 groups. Our results indicate that the properties of these ILs are highly affected by the presence of OH and CF3 groups, in which OH stabilizes the negative charge of the anion via intramolecular hydrogen bonds and CF3 stabilizes it through the electron withdrawing effect. These groups decrease the binding energy between the anion and cation of the carboxylate-based ionic liquids and thus affect their physical properties such as melting point and density as well as their chemical properties. All calculations in this study were performed in the gas phase at the B3LYP/6-311++G(d,p) level. [ABSTRACT FROM AUTHOR]

Density functional theory method and B3LYP/6‐311++G(d,p) level of theory were used to determine the acidity of α‐carbon in the hydroxyl derivatives of beta diketones in the gas phase. An investigation of acidity strength in the gas phase indicates that α‐carbon of hydroxyl derivatives of beta diketones become stronger acids than the α‐carbon of beta diketone itself as their conjugate bases gain more stability via both enolate and hydrogen bond formation. Natural bond orbital and quantum theory of atoms in molecules analyses also confirm the role of hydrogen bond interactions on increasing the acidity of α‐carbon of hydroxyl derivatives of beta diketones. [ABSTRACT FROM AUTHOR]

The unusual monosaccharaides such as deoxy‐hexose sugars, including methyl‐pentose and aldo‐pentose, are promising and important sugars in life science. However, little research on H‐bond interactions in these systems has been reported. The aldo‐pentose has a proton instead of the CH2OH group on C5; conversely, methyl‐pentose has a CH3 group on C5. The aim of the present study is to investigate the role and nature of intramolecular H‐bonds on acidity of CH3‐pentose sugars (L‐fucose and L‐rhamnose) and aldo‐pentose sugars (D‐xylose, L‐lyxose, D‐ribose, and L‐arabinose) using B3LYP/6‐311++G (d, p) level. The calculated acidity values (ΔHacid) of these Dexoy‐hexose were found to be from 343 to 369 kcal.mol−1, indicating they are stronger acid than ethanol and 2‐propanol with the acidity values of 378.3 and 375.1 kcal.mol−1, respectively. This is related to the stabilization of the conjugate bases of these sugar through intramolecular H‐bonds, which were analyzed in this study using atoms in molecules (AIM) and natural bonding orbital (NBO) methods. AIM and NBO analyses indicate the presence of one bifurcated intramolecular H‐bond in the conjugate bases of L‐lyxose and L‐arabinose and two bifurcated H‐bonds in conjugate base of D‐ribose, whereas the conjugate bases of L‐fucose, L‐rhamnose, and D‐xylose present one normal intramolecular H‐bond. According to the topological parameters and charge transfer data, existence of normal and bifurcated intramolecular H‐bonds could greatly increase acidity of deoxy‐hexose sugars. The H‐bond strength in the conjugate bases of aldo‐pentose sugars is higher than that in the conjugate bases of methyl‐pentose sugars including CH3 group on C5, making aldo‐pentose sugars stronger acid than methyl‐pentose sugars. [ABSTRACT FROM AUTHOR]

Abstract: In this study, the structural and electronic properties of a carbohydrate‐based (6‐amino‐6‐deoxy hexopyranose [ADHP]) ionic liquid were explored. The interactions among 3 anions (BF4¯, PF6¯, and ClO4¯) and ADHP as cation were investigated at B3LYP/6‐311++G(d,p) level. Based on the calculated interaction energy, it was found that PF6¯ anion has the highest interaction energy with ADHP. It was found that the hydrogen bonds play an important role in the interaction of ion pairs. The nature of hydrogen bonds in the optimized ion pars was analyzed by using natural bond orbital analysis and the quantum theory of atoms in molecules. The linear relationship between electron density at the bond critical points of hydrogen bonds and the interaction energy values was checked. [ABSTRACT FROM AUTHOR]

Abstract: The free radical activity of lespedezacoumestan was investigated toward hydroxyl (˙OH) radical in polar and nonpolar media using density functional theory. Four reaction mechanisms including radical adduct formation, hydrogen atom transfer, sequential single electron‐proton transfer (SET‐PT), and sequential proton loss electron transfer were considered. The rate constants and branching ratio for all possible sites of reaction were calculated and reported for the first time. According to the obtained results, lespedezacoumestan reacts faster with ˙OH radical in aqueous solution than in nonpolar media. Also, lespedezacoumestan is an excellent ˙OH radical scavenger regardless of the environment polarity. [ABSTRACT FROM AUTHOR]

Polyols were used as model ligands for Mg2+, Ca2+, and Zn2+ complexes to study the role of the hydrogen bond network on the metal binding affinity and modulation of successive pKa values using density functional theory. The results confirm that the acidity of polyols dramatically increases upon metal complexation in the order Zn2+ ＞ Mg2+ ＞ Ca2+. For example, the three H-site positions in the hydroxyl groups of the heptaol, bound to Zn2+, are 11.2, 29.9, and 30.9 pKa units (in methanol) more acidic than those of pure heptaol. This acidity enhancement leads to making polyols as good ligands toward complexation. For instance, the formation constants of the heptaol in the presence of Zn2+, Mg2+, and Ca2+ in methanol were 5.67 × 1071, 6.46 × 1066, and 1.26 × 1053 times lower than those in its third deprotonation state, respectively. The natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM), and reduced density gradient (RDG) analyses show that the intramolecular hydrogen bond network and increment of carbon chain length lead to the enhancement of metal binding affinity. These findings can be used for the manipulation of ligands and metal cations in designing metalloproteins. [ABSTRACT FROM AUTHOR]

In this work, the antioxidant ability of fisetin was explored toward hydroxyl (•OH) radical in aqueous and lipid solution using density functional level of theory. Different reaction mechanisms have been studied: hydrogen atom transfer, single electron transfer followed by proton transfer, and radical adduct formation, and sequential proton loss electron transfer. Rate constants for all possible reaction sites have been calculated using conventional transition state theory in conjunction with the Collins-Kimball theory. Branching ratios for the different channels of reaction are reported for the first time. Results show that the reactivity of fisetin toward hydroxyl (•OH) radical takes place almost exclusively by radical adduct formation regardless of the polarity of the environment. Also, the single-electron transfer process seems to be thermodynamically unfavorable in both media. [ABSTRACT FROM AUTHOR]

The equilibrium acidity of styrene was measured (Δ H ° acid (PhCH CH 2 ) = 390.6 ± 0.5 kcal mol −1 ) and its deprotonation site was revised from the ortho position on the aromatic ring to the α-hydrogen atom based upon deuterium-labeling studies and extensive computations. Somewhat surprisingly, the nature of the anionic base plays a critical role in properly determining the ionization site and avoiding misleading results due to extraordinary hydrogen–deuterium exchange. Bracketing the electron affinity of α-styryl radical (PhC CH 2 , 23.1 ± 3.4 kcal mol −1 ) enabled the α-C H bond dissociation energy (100.1 ± 3.4 kcal mol −1 ) of styrene and the effect of a phenyl substituent at an sp 2 -hybridized carbon to be determined. These results were compared to B3LYP, M06-2X, G3 and G4 computations. [ABSTRACT FROM AUTHOR]

The α-C-H bond dissociation energy (BDE) of phenylcyclopropane (1) was experimentally determined using Hess' law. An equilibrium acidity determination of 1 afforded ΔH°acid = 389.1 ± 0.8 kcal mol-1, and isotopic labeling established that the α-position of the three-membered ring is the favored deprotonation site. Interestingly, the structure of the base proved to be a key factor in correctly determining the proper ionization site (i.e., secondary amide ions are needed, and primary ones and OH- lead to incorrect conclusions since they scramble the deuterium label). An experimental measurement of the electron affinity of 1-phenylcyclopropyl radical (EA = 17.5 ± 2.8 kcal mol-1) was combined with the ionization energy of hydrogen (313.6 kcal mol-1) to afford BDE = 93.0 ± 2.9 kcal mol-1. This enabled the effect of the phenyl substituent to be evaluated and compared to other situations where it is attached to an sp³- or sp²-hybridized carbon center. M06-2X, CCSD(T), G4, and W1BD computations were also carried out, and a revised C-H BDE for cyclopropane of 108.9 ± 1.0 kcal mol-1 is recommended. [ABSTRACT FROM AUTHOR]

• A cooperative network of trifurcated and bifurcated in addition to normal H-bonds were found in the conjugate base of O-Gal. In contrast, bifurcated and normal H-bond were observed in the conjugate base of cyclic galactose and neutral form of O-Gal. • Based on acidity values (Δ H a c i d ), galactose in open form (O-Gal) is more acidic than its cyclic form (Gal). • The acidity value for galactose in open and cyclic forms exhibit significantly lower values (i.e., stronger acid) compared to the reported acidity value for α-/ß- anomers of D-glucopyranose and simple alcohols because their conjugate bases are more stabilized through intramolecular H-bonds like trifurcated and bifurcated H-bonds. In this work, the intramolecular H-bonds in galactose were studied using DFT at the B3LYP/6–311++G (d,p) levels of theory, atoms in molecules (AIM), and natural bond orbital (NBO). AIM and NBO analysis revealed a cooperative network of trifurcated, bifurcated, and normal H-bonds for the conjugate bases of open galactse (O-Gal). While for the conjugate base of the cyclic form of galactose, we identified bifurcated and normal H-bonds, which may highlight a crucial feature of the biological activity of a whole class of natural sugars. The O-H...O bonds are categorized as mostly electrostatic, strong H-bonds and more favorable, whereas for multiple interactions involving C=O...H, C-H...O and C-H...H-C (dihydrogen bonding) interactions are categorized as weak H-bonds bonds in the conjugate base of considered sugar. The theoretical results indicated that based on acidity values (Δ H a c i d ), galactose in open form (O-Gal) is more acidic than cyclic form (Gal).The acidity value for galactose in open and cyclic forms exhibit significantly lower values (i.e., stronger acid) compared to the reported acidity value for α-/ß- anomers of D-glucopyranose and simple alcohols because their conjugate bases are more stabilized through intramolecular H-bonds like trifurcated and bifurcated, which are studied in details using AIM and NBO analysis. [ABSTRACT FROM AUTHOR]

The heat of hydrogenation of indenone was measured via two partially independent thermodynamic cycles by carrying out energetic measurements (i.e., electron affinities, proton affinities and ionization potentials) on both negative and positive ions (Δ H ° H 2 = 17.8 ± 5.5 and 17.5 ± 5.7 kcal mol −1 , respectively). High level G3 computations were also carried out to provide the heats of formation of indenone (16.8 kcal mol −1 ) and cyclopentadienone (14.0 kcal mol −1 ). These 4 n π electron systems are found to be nonaromatic in contrast to previous views. A recent report on cyclopropenyl anion (J. Org. Chem. 2013, 78, 7370–7372) indicates that this ion is also nonaromatic, and suggests that NMR ring currents and nucleus independent chemical shift (NICS) calculations do not correlate with the energetic criterion for antiaromatic compounds. [ABSTRACT FROM AUTHOR]

The heat of hydrogenation of indenone was measured via two partially independent thermodynamic cycles by carrying out energetic measurements (i.e., electron affinities, proton affinities and ionization potentials) on both negative and positive ions (ΔH°H2 = 17.8 ± 5.5 and 17.5 ± 5.7 kcal mol-1, respectively). High level G3 computations were also carried out to provide the heats of formation of indenone (16.8 kcal mol-1) and cyclopentadienone (14.0 kcal mol-1). These 4n π electron systems are found to be nonaromatic in contrast to previous views. A recent report on cyclopropenyl anion (J. Org. Chem. 2013, 78, 7370-7372) indicates that this ion is also nonaromatic, and suggests that NMR ring currents and nucleus independent chemical shift (NICS) calculations do not correlate with the energetic criterion for antiaromatic compounds. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) was used to investigate the acidity of the various silica alkyl sulfonic acids. In this regard, cluster models with various alkyl spacer lengths were selected to mimic the surface of silica gel. The effects of distance from the surface and the role of hydrogen bond (H–bond) on the ΔHacidityvalues of these catalysts were investigated. DFT calculations revealed that a notable gap of ΔHacidityvalues exists between the structures considering lateral hydrogen bonding with the surface of the silicaHB structureand the structures with omitted surface interactions (non-HB structures). Natural bonding orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses were carried out to obtain detailed information about the nature of the H–bonds. [ABSTRACT FROM AUTHOR]

Silica gelâ€confined ionic liquid (IL) is a class of heterogeneous catalysts with broad catalytic applications. Leaching of the IL from the surface of the support is the major drawback of these catalysts, which reduce the catalyst efficiency during the chemical reactions. To investigate the effect of the hydrogen bonding on the leaching phenomena, the interaction between the 1â€ethylâ€3â€methylimidazoliumâ€based IL with various anions (Clâˆ', Brâˆ', HSO4âˆ', NO3âˆ', BF4âˆ', and PF6âˆ') and the surface of the silica gel were studied using density functional theory. Hence, a hydroxylated cageâ€like cluster of silica gel, Si4O6(OH), was selected to mimic the surface. The values of Î'Einteraction show that ILs with halogen counter ions have stronger interactions than that of the IL with BF4âˆ' and PF6âˆ' counter ions. We also carried out stirringâ€'filtration method for some prepared samples of IL@silica to experimentally explore the leaching phenomena. The results show good agreement with computational achievements. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In recent years, there has been increasing interest in damaged DNA and RNA nucleobases. These damaged nucleobases can cause DNA mutation, resulting in various diseases such as cancer. Alkylating agents are mutagenic and carcinogenic in a variety of prokaryotic and eukaryotic organisms. The present study employs density functional theory (DFT/B3LYP) with the 6-311++G(d,p) basis set to investigate the effect of chemical damage in O-alkyl pyrimidines such as O-methylthymine, O-methylcytosine and O-methylthymine. We compared the intrinsic properties, such as proton affinities, gas phase acidities, equilibrium tautomerization and nucleobase pair's hydrogen bonding properties, of these molecules with those in the normal nucleobases thymine and cytosine. The results are of interest for chemical reasons and also possibly for biological purposes since biological media can be quite non-polar. Furthermore, we found that N1-H of O-methylthymine is less acidic than N1-H of thymine, suggesting that alkyl DNA glycosylase enzyme cannot discriminate this damaged nucleobase from a normal thymine nucleobase. This result indicates that the conjugated base anion of O-methylthymine would be a worse leaving group and O-methylthymine is repaired in genome by demethylation rather than enzyme-catalyzed excision at N1. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) method and B3LYP/6-311++G(d,p) basis set were used to determine coordination geometries, binding strength, and metal ion affinity (MIA) for interaction of 2′-deoxythymidine (dT) with alkali metal cations including , and . Calculations demonstrated that the interaction of dT with these cations is tri-coordinated η (O2, O4′, O5′). Among these cations, cation exhibited the most tendency for interaction with dT. Cations via their interaction with dT can affect the N-glycosidic bond length, the values of pseudorotation of the sugar ring, the orientation of base unit with respect to sugar ring and the acidity of O5′H, O3′H, and N3H groups in 2′-dT nucleoside. Natural bond orbital (NBO) analysis was performed to calculate the charge transfer and natural population analysis of the complexes. Quantum theory of atoms in molecules (QTAIM) was also applied to determine the nature of interactions. It was shown that in these complexes, (dT-, dT-, and dT-), the bonds are an electrostatic (closed-shell) interaction in the nature. [ABSTRACT FROM AUTHOR]

Glutathione tripeptide (γ-glutamyl-cysteinyl-glycine) is a flexible molecule and its conformational energy landscape is strongly influenced by forming intramolecular hydrogen bond, its charge and the environment. This study employs DFT-B3LYP method with the 6-31+G (d,p) basis set to carry out conformational analysis of neutral, zwitterionic, cationic, and anionic forms of glutathione. In analyzing the structural characteristics of these structures, intramolecular hydrogen bonds were identified and characterized in details by topological parameters such as electron density ρ( r) and Laplacian of electron density $$ \nabla^{2} $$ρ( r) from Bader's atom in molecules theory. Charge transfer energies based on natural bond orbital analysis are also considered to interpret these intramolecular hydrogen bonds. Our results show that these hydrogen bonds are partially electrostatic and partially covalent in nature, in which the covalent contribution increases as the stabilization energy of hydrogen bond increases. Furthermore, the back bone and side chain (Ramachandran map) orientations of various ionic forms of glutathione have been studied and conformation of each constitution of glutathione tripeptide (i.e., Glu, Cys, and Gly moieties) was determined. In most species side chain conformation were found to be hindered gauche-gauche orientation by intramolecular hydrogen bonds. [ABSTRACT FROM AUTHOR]

Thiotepa ( N,N′, N″-triethylenethiophosphoramide) and its major metabolite (Tepa) as trifunctional alkylating agents has recently been used in cancer therapy. In vivo and vitro studies show the possible pathways of alkylation of DNA by Thiotepa and Tepa. Two pathways are suggested, but the main pathway of mechanism remains unclear. In pathway 1, forming cross-links with DNA molecules can be carried out via two different mechanisms. In first mechanism, these agents undergo the ring opening reaction which is initiated by protonating aziridine, which then becomes the main target of nucleophilic attack by the N7-Guanine of DNA. The second probable mechanism is ring opening of aziridyl group by nucleophilic attack of N7-Guanine without initial protonation. Thiotepa and Tepa in pathway 2, act as a cell penetrating carrier for aziridine, which is released via hydrolysis. The released aziridine can form a cross-link with N7-Guanine. In this study, we calculated the activation free energy and kinetic rate constant for alkylating the Guanine via the first pathway to determine the most precise mechanism by applying density functional theory using B3LYP method. We carried out geometrical optimizations with the conductor-like polarizable continuum model to account for the solvent effect, and the results were compared with those in the gas phase. Hyperconjugation stabilization factors that affect on stability of generated transition state were investigated by natural bond order analysis. Furthermore, quantum theory of atoms in molecules analysis was performed to extract the bond critical points properties because the electron densities can be considered as a good description of the strength of different types of interactions. [ABSTRACT FROM AUTHOR]

N,N′,N″-triethylenethiophosphoramide (Thiotepa) and its oxo analogue (Tepa) as the major metabolite are trifunctional alkylating agents with a broad spectrum of antitumor activity. In vivo and vitro studies show alkylation of DNA by Thiotepa and Tepa can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. In pathway 1, these agents are capable of forming cross-links with DNA molecules via two different mechanisms. In the first mechanism, the ring opening reaction is initiated by protonating the aziridine, which then becomes the primary target of nucleophilic attack by the N7-Guanine. The second one is a direct nucleophilic ring opening of aziridyl group. Thiotepa and Tepa in pathway 2, act as a cell penetrating carrier for aziridine, which is released via hydrolysis. The released aziridine can form a cross-link with N7-Guanine. In this study, we calculated the activation free energy and kinetic rate constant for hydrolysis of these agents and explored interaction of aziridine with Guanine to predict the most probable mechanism by applying density functional theory (DFT) using B3LYP method. In addition, solvent effect was introduced using the conductor-like polarizable continuum model (CPCM) in water, THF and diethylether. Hyperconjugation stabilization factors that have an effect on stability of generated transition state were investigated by natural bond order (NBO) analysis. Furthermore, quantum theory of atoms in molecules (QTAIM) analysis was performed to extract the bond critical points (BCP) properties, because the electron densities can be considered as a good description of the strength of different types of interactions. [ABSTRACT FROM AUTHOR]

The interactions between five amino acid based anions([AA]−(AA = Gly, Phe, His, Try, and Tyr)) and N7,N9-dimethylguaniniumcation ([dMG]+) have been investigated by the hybrid densityfunctional theory method B3LYP together with the basis set 6-311++G(d,p).The calculated interaction energy was found to decrease in magnitudewith increasing side-chain length in the amino acid anion. The interactionbetween the [dMG]+cation and [AA]−anionin the most stable configurations of ion pairs is a hydrogen bondinginteraction. These hydrogen bonds (H bonds) were analyzed by the quantumtheory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. Finally, several correlations between electron densities inbond critical points of hydrogen bonds and interaction energy as wellas vibrational frequencies in the most stable configurations of ionpairs have been checked. [ABSTRACT FROM AUTHOR]

Bridgehead C-H bond dissociation enthalpies of 105.7 ± 2.0, 102.9 ± 1.7, and 102.4 7plusmn; 1.9 kcal mol-1 for bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, and adamantane, respectively, were determined in the gas phase by making use of a thermodynamic cycle (i.e., BDE(R-H) = ΔHºacid(H-X) - IE(H) + EA(X)). These results are in good accord with high-level G3 theory calculations and the experimental values along with G3 predictions for bicyclo[1.1.1]pentane, bicyclo[2.2.1]hexane, bicyclo[3.1.1]heptane, and bicyclo[4.2.1]nonane the gas found to correlate with the flexibility of the ring system. Rare examples of alkyl anions in the gas phase are also provided. [ABSTRACT FROM AUTHOR]

Hydrogen bonding interactions between thymine nucleobase and 2′-deoxythymidine nucleoside (dT) with some biological anions such as F (fluoride), Cl (chloride), OH (hydroxide), and NO (nitrate) have been explored theoretically. In this study, complexes have been studied by density functional theory (B3LYP method and 6-311++G (d,p) basis set). The relevant geometries, energies, and characteristics of hydrogen bonds (H-bonds) have been systematically investigated. There is a correlation between interaction energy and proton affinity for complexes of thymine nucleobase. The nature of all the interactions has been analyzed by means of the natural bonding orbital (NBO) and quantum theory atoms in molecules (QTAIM) approaches. Donors, acceptors, and orbital interaction energies were also calculated for the hydrogen bonds. Excellent correlations between structural parameter (δ R) and electron density topological parameter ( ρ) as well as between E(2) and ρ have been found. It is interesting that hydrogen bonds with anions can affect the geometry of thymine and 2′-deoxythymidine molecules. For example, these interactions can change the bond lengths in thymine nucleobase, the orientation of base unit with respect to sugar ring, the furanose ring puckering, and the C1′-N1 glycosidic linkage in dT nucleoside. Thus, it is necessary to obtain a fundamental understanding of chemical behavior of nucleobases and nucleosides in presence of anions. [ABSTRACT FROM AUTHOR]

Binding of Mg2+, Ca2+, Zn2+, and Cu+ metal ions with 2′-deoxythymidine (dT) nucleoside was studied using a density functional theory method and a 6-311++G(d,p) basis set. This work demonstrated that the interaction of dT with these cations is tri-coordinated η (O2, O4′, O5′). Among the four types of cations, Zn2+ cation exhibited the most tendency to interact with the dT. Cations via their interaction with dT can affect the N-glycosidic bond length, the values of pseudorotation of the sugar ring, the orientation of the base unit with respect to the sugar ring, and the acidity of the O5′H, O3′H, and N3H groups in the dT nucleoside. Natural bond orbital analysis was performed to calculate the charge transfer and natural population analysis of the complexes. Quantum theory of atoms in molecules was also applied to determine the nature of interactions. It was shown that in dT-Mg2+ and dT-Ca2+ complexes, the bonds are electrostatic (closed-shell) interactions, although they are partially covalent and partially electrostatic interactions in dT-Zn2+ and dT-Cu+ complexes. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this paper, we explore theoretically energetic and structural properties of the possible cations formed via hydride ion abstraction at various sites of sugar part of cytosine nucleosides by employing B3LYP exchange-correlation functional with 6-311++G (d,p) orbital basis sets. In general, the hydride ion abstracted sugar cations of cytosine nucleosides have the following stability sequence: caH2′ > caH1′ > caH3′ > caH4′ > caH5′ for cytidine and caH1′ > caH4′ > caH3′ > caH5′ > caH2′ for deoxycytidine. Furthermore, the effect of solvent environment on the stability order of cations integral equation formalism of the polarized model (IEF-PCM) was employed to model aqueous solution. The natural bond orbital method was used for quantitative analysis of the electron delocalization donor-acceptor interaction of various hydride ions abstracted centers of cytosine nucleosides. The role of CH⋯O and HO⋯H intramolecular hydrogen bonds in the stability of cations is investigated based on the results of topological properties of atom in molecule theory. Moreover, variations of significant structural parameters such as puckering amplitudes and phase angles of sugar parts of cytosine nucleosides after cation formation are also found. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) calculations were performed at the B3LYP/6-311++G(d, p) level to determine coordination geometries, absolute metal ion affinities, and free energies for all possible complexation stable products formed by monovalent metal cations including Li+, Na+, K+ with the nucleoside 2′-Deoxyguanosine. All computations indicate that the metal ion affinity (MIA) decreases on going from Li+ to Na+ and K+ for 2′-Deoxyguanosine. For example, the affinities for the metal ions described above are 75.2, 57.3, 43.4 kcal/mol, respectively. Furthermore, the influence of metal cationization and O6 protonation on the strength of the N-glycosidic bond, torsion angles and angle of pseudorotation (P) have been studied. With respect to the results, it has been found that metal binding significantly change the values of the phase angle of pseudorotation (P) in the sugar unit of these nucleosides but, O6-protonation do not significantly change the values of the torsion angles and angle of pseudorotation (P). In all modified forms, the length of the C1'–N9 bond increases. The Mulliken population analysis and natural bond orbital (NBO) analysis on atomic charges have been carried out on the optimized geometries. [ABSTRACT FROM AUTHOR]

Electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) combined with H/D exchange reactions was utilized to explore the existence of different b5 + and b4 + fragment ion conformers/isomers of hexapeptide WHWLQL in the gas phase. Distinct H/D exchange trends for protonated WHWLQL ([M + H]+) and its b5 + and b4 + fragment ions (with ND3) were observed. Isolated 12Call isotopomers of both b5 + and b4 + fragment ions yielded bimodal distributions of H/D exchanged product ions. The H/D exchange reaction kinetics also confirmed that b5 + and b4 + fragment ions exist as combination of slow-exchanging (“s”) and fast-exchanging (“f”) species. The calculated rate constant for the first labile hydrogen exchange of [M + H]+ (k[M + H]+ = 3.80 ± 0.7 × 10–10 cm3 mol–1 s–1) was ∼30 and ∼5 times greater than those for the “s” and “f” species of b5 +, respectively. Data from H/D exchange of isolated “s” species at longer ND3 reaction times confirmed the existence of different conformers or isomers for b5 + fragment ions. The sustained off-resonance irradiation collision-activated dissociation (SORI-CAD) of WHWLQL combined with the H/D exchange reactions indicate that “s” and “f” species of b5 + and b4 + fragment ions can be produced in the ICR cell as well as the ESI source. The significance of these observations for detailed understanding of protein sequencing and ion fragmentation pathways is discussed. [Copyright &y& Elsevier]

Hydrogen bonds are the dominant motif for organizing the three-dimensional structures of biomolecules such as carbohydrates, nucleic acids, and proteins, and serve as templates for proton transfer reactions. Computations, gas-phase acidity measurements, and pKa determinations in dimethyl sulfoxide on a series of polyols indicate that multiple hydrogen bonds to a single charged center lead to greatly enhanced acidities. A new class of Brønsted acids, consequently, is proposed. [ABSTRACT FROM AUTHOR]

Abstract: The noncovalent interactions between cytosine nucleobase with some biological anions such as F−, Cl−, CN−, , and OH− and cytosine nucleosides (i.e., cytidine and deoxycytidine molecules) with F−, Cl−, CN− anions have been demonstrated by DFT study. The molecular geometries, energy properties, H-bonding patterns, dipole moments and charge distribution of these complexes were investigated with the B3LYP method in conjunction with the 6-311++G(d,p) basis set. It has been found that anions can interact with cytosine nucleobase forming hydrogen bonds. In general, these interactions occur via N–H, O–H and C–H substituents of cytosine, cytidine and deoxycytidine. The presence of anions near these molecules strongly affects the electron distribution in the base structure. From this study, a greater understanding of hydrogen bonding interactions involving DNA and RNA molecules will be obtained. These interactions could provide insight to an unrecognized control element in biological processes, providing new and intriguing opportunities of exploring the electrostatic effects on biological processes. [Copyright &y& Elsevier]

Abstract: The coordination geometries, electronic features, absolute metal ion affinities, geometrical multiplicity and binding strength for the complexes formed by Mg2+, Ca2+, Zn2+ and Cu+ with cytidine and deoxycytidine have been determined theoretically employing the hybrid B3LYP exchange-correlation functional and using 6-311++G(d,p) orbital basis sets. Our study shows that the most stable coordination modes of cytosine nucleosides with these cations are rather similar. In the isolated state, the most stable form corresponds to a tridentate complex in which the cation interacts with three oxygen atoms: one from the carbonyl oxygen of cytosine moiety and two from the sugar unit (i.e., O5′ and O4′). The influences of metal cationization on the strength of the N-glycosidic bond, the values of the phase angle of pseudorotation P in the sugar unit and sugar ring conformation have been studied. In all cases, the N1; bond distance changes upon introducing positive charge in the nucleosides. [Copyright &y& Elsevier]

In view of better understanding interactions of amino acids and peptides with metallic cations in the isolated state, the model system histidine–M2+ (M2+ = Mg2+, Ca2+, Zn2+) has been studied theoretically. The computations have been performed with the help of the density functional theory (DFT) and the B3LYP functional. The extended basis set was the standard 6-311++G**. All the molecular complexes obtained by the interaction between several energetically low-lying tautomers/conformers/zwitterions of histidine and the cations on different binding sites were considered. Our study shows that complexes of histidine with Mg2+, Ca2+, Zn2+ are rather similar. In the isolated state, the most stable form corresponds to a tridentate complex in which the cation interacts with oxygen and two nitrogen atoms: one from the terminal NH2 and one from the imidazole ring. All computations indicate that the metal ion affinity (MIA) decreases on going from Zn2+ to Mg2+ and Ca2+, for the considered amino acid. This indicates that histidine prefers to bind to the transition metal cation rather than alkali earth metals. The influence of theses cations on the acidity of histidine were also considered. As expected, upon metal complexation, proton dissociation of histidine becomes much more favorable, that is, its acidity becomes much less endothermic. [ABSTRACT FROM AUTHOR]

The gas-phase metal affinities of histidine Li+, Na+ and K+ ions have been determined theoretically employing the hybrid B3LYP exchange–correlation functional and using 6-311++G** basis sets. All computations indicate that the metal ion affinity decreases on going from Li+ to Na+ and K+ for the considered amino acid. Different types of M+ coordinations on several histidine conformers/tautomers were considered in detail. The optimized structures indicate that Li+ and Na+ prefer a tri-dentate coordination, bonding with a nitrogen atom of imidazole ring (Nτ), –NH2, and an oxygen atom of a carbonyl, while in the K+-histidine lowest-energy conformer, the cation appears to be bi-coordinated to both oxygen atoms of the zwitterionic form by the energy values not too far from that of tri-coordination. We also performed the DFT calculations for proton dissociation energy of histidine both in the presence and absence of alkali metal ions. Our results also reveal that the acidity of histidine dramatically increases upon metal ion complexation. [ABSTRACT FROM AUTHOR]

Abstract: Density functional theory (DFT) calculations were performed at the B3LYP level with a 6-311++G(d,p) basis set to systematically explore the geometrical multiplicity and binding strength for complexes formed by Li+, Na+, and K+ with cytidine and 2′-deoxycytidine. All computational studies indicate that the metal ion affinity (MIA) decreases from Li+ to Na+ and K+ for cytosine nucleosides. For example, for cytidine the affinity for the above metal ions are 79.5, 55.2, and 41.8 and for 2′-deoxycytidine, 82.8, 57.4, and 42.2kcal/mol, respectively. It is also interesting to mention that linear correlations between calculated MIA values and the atomic numbers (Z) of the above metal ions were found. The influence of metal cationization on the coordination modes and the strength of the N-glycosidic bond in cytosine nucleosides have been studied. In all cases, the N1–C1′ bond distance changes upon introducing a positive charge in the nucleosides. It has been found that metal binding significantly changes the values of the phase angle of pseudorotation P in the sugar unit of these nucleosides. With respect to the sugar ring, metal binding changes the values of the glycosyl torsion angle and sugar ring conformation. The present calculations in the gas phase provide the first clues on the intrinsic chemistry of these systems and may be of value for studies of the influence of metal cations on the conformational behavior and function of nucleic acids. [Copyright &y& Elsevier]

B3LYP/aug-cc-pVDZ computations were carried out on polyamines with up to seven amino groups. The gas-phase proton affinities of these compounds are 219.6 (1-BuNH2), 238.6 (H2NCH2CH2CH2CH2NH2), 252.8 [(H2NCH2CH2CH2)2CHNH2], 261.3 [(H2NCH2CH2CH2)3CNH2 (1)], and 288.5 kcal mol-1 [(H2NCH2CH2CH(NH2)CH2CH2)3CNH2]. These results indicate that the tetraamine is near the top of the basicity scale and the heptaamine is more basic than any neutral organic compound which has been measured to date. A gas-phase equilibrium acidity determination between 1 and DBU also was carried out, and PA(1) = 256.2 ± 2.1 kcal mol-1 was obtained. This demonstrates that multiple intramolecular hydrogen bonds can greatly increase basicities, and represents a new motif for designing super bases. [ABSTRACT FROM AUTHOR]

Abstract: We have compared the gas phase thermochemical properties of aspartame (artificial sweetener) and α- and β-glucose. These parameters include metal ion affinities with Li+-, Na+-, K+-, Mg+2-, Ca+2-, Fe+2-, Zn+2-ions, and chloride ion affinity by using DFT calculations. For example, for aspartame, the affinity values for the above described metal ions are, respectively, 86.5, 63.2, 44.2, 255.4, 178.4, 235.4, and 300.4, and for β-glucose are 65.2, 47.3 32.9, 212.9, 140.2, 190.1, and 250.0kcalmol−1, respectively. The study shows differences between the intrinsic chemistry of aspartame and glucose. [Copyright &y& Elsevier]

The effects of selected metal ions on the gas-phase acidity of weak organic acids have been explored using the DFT and Moller–Plesset Perturbation Theory (MP2) calculations. The three organic acids selected for this study were acetic acid (aliphatic), benzoic acid (aromatic), and glycine (amino acid). The acidities of these compounds are compared with the acidity of their Li+-, Na+-, and K+-complexed species. The results indicate that upon complexation with Li+, Na+, and K+ at 298 K, the gas-phase acidity of acetic acid, for example, varies from 345.3 to 218.8, 230.2, and 240.1 kcal/mol, respectively (i.e., its dissociation becomes much less endothermic). These values indicate that a weak organic acid can be converted to a super acid when it is complexed with an ionic metal. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Both C-H bond dissociation energies for cyclobutene were measured in the gas phase (BDE = 91.2 ± 2.3 (allyl) and 112.5 ± 2.5 (vinyl) kcal mol-1) via a thermodynamic cycle by carrying out proton affinity and electron-binding energy measurements on 1- and 3-cyclobutenyl anions. The results were compared to those for an acyclic model compound, cis-2-butene, and provide the needed information to experimentally establish the heat of formation of cyclobutadiene. Chemically accurate G3 and W1 calculations also were carried out on cycloalkanes, cycloalkenes, and selected reference compounds. It appears that commonly cited bond energies for cyclopropane, cyclobutane, and cyclohexane are 3 to 4 kcal mol-1 too small and their π bond strengths, as given by BDE1 - BDE2, are in error by up to 8 kcal mol-1. [ABSTRACT FROM AUTHOR]

The heat of hydrogenation of phenylcyclobutadiefle (ΔHohyd = 57.4 ± 4.9 kcal mol-1) was determined via a thermodynamic cycle by carrying out gas-phase measurements on 1 -phenylcyclobuten-3-yl cation. This leads to an antiaromatic destabilization energy of 27 ± 5 kcal mol-1, a difference of 9.6 ± 4.9 kcal mol-1 for the first and second C—H bond dissociation energies of 1 -phenylcyclobutene, and an estimate of 96 ± 5 kcal mol-1 for the heat of formation of cyclobutadiene. These results are compared to G3, G3(MP2), and B3LYP computations and represent the first experimental measurements of the energy of a monocyclic cyclobutadiene. [ABSTRACT FROM AUTHOR]

Radical anions of O-, m-, and p-benzoquinone were produced in a Fourier transform mass spectrometer by low energy electron attachment or collision-induced dissociation and were differentiated. Classical derivatization experiments also were carried out to authenticate the ortho and meta anions. Gas- phase techniques were used to measure the proton affinities of all three radical anions and the electron affinities of o- and m-benzoquinone. By combining these results in thermodynamic cycles, we derived heats of hydrogenation of o-, m-, and p-benzoquinone (AhydHo(1O, 1m, and 1p) = 42.8 ± 4.1, 74.8 ± 4.1, and 38.5 ± 3.0 kcal mol-1, respectively) and their heats of formation (Ad-P(1o, 1 m, and Ip) = -23.1 ± 4.1, 6.8 ± 4.1, and -27.7 ± 3.0 kcal mol-1, respectively). Good accord with the literature value for the para derivative was obtained. Combustion calorimetry and heats of sublimation also were measured for benzil and 3,5- di-tert-butyl-o-benzoquinone. The former heat of formation agreed with previous determinations, while the latter result (AfI-f(g) = -73.09 ± 0.87 kcal mol-1) was transformed to A1H°(lo) = -18.9 ± 2.2 kcal mol-1 by removing the effect of the tert-butyl groups via isodesmic reactions. This led to a final value of AH°(10) = -21.0 ± 3.1 kcal mol-1. Additivity was found to work well for m-benzoquinone, but BDE1 and BDE2 for 1,2- and I ,4-dihydroxybenzene differed by a remarkably small 14.1 ± 4.2 and 23.5 ± 3.7 kcal mol1, respectively, indicating that o- and p-benzoquinone should be excellent radical traps. [ABSTRACT FROM AUTHOR]

Bond energies, acidities, and electron affinities are related in a thermodynamic cycle, and by measuring two of these quantities one can derive the third. This procedure is most often used to determine bond dissociation energies. In this work, we show that ΔHOacid(HX), EA(X), and BDE(HX) are all linearly related for specific classes of compounds (e.g., alcohols and carboxylic acids), and therefore, only one of these quantities is needed to determine the others. This should simplify thermodynamic determinations and enable hundreds of new values to be obtained from already existing data in the literature. The intercepts obtained from plots of ΔHOacid(HX) vs EA(XO provide bond energies which correspond to BDE(HX) when EA(X) = 0. The results for eight different types of compounds are provided and some of these values are discussed. Sensitivity factors are obtained from the slopes of these plots, and their sign (+ vs -) can be predicted by considering physical effects such as hybridization and resonance. [ABSTRACT FROM AUTHOR]

A systematic treatment of chemical equilibria is used to determine the average molecular weight (AMW) of the Suwannee River fulvic acids directly from aqueous solutions. In addition to molecular weight determination, parameters such as equilibrium constant and reaction stoichiometry can be calculated; in this approach, it is not necessary to measure the initial mass of unknown analytes. The key experimental and theoretical considerations for systematic treatment of equilibrium and determination of unknown parameters are addressed. Results from the equilibrium considerations yield an AMW of 551±10 Da for the Suwannee River fulvic acid sample analyzed in this study. In addition to the Suwannee River fulvic acid sample, experimental data for selected monoprotic and polyprotic acids are presented and discussed. [Copyright &y& Elsevier]

Measures the gas-phase acidity of 3,3-dimethylcyclopropene by bracketing and equilibrium techniques. Evidence showing that the derived value is indistinguishable from that of methylacetylene; Electron affinity of 3,3-dimethylcyclopropenyl radical.

The derivatives of glucose such as glucosamine (β-D-GlcN) and N-acetyl-D-β-glucosamine (GlcNAc) are significant in several biological systems. D-GlcN has been used widely to treat osteoarthritis in humans and animal models as well as GlcNAc has been proposed as a treatment for autoimmune diseases. The DFT/B3LYP/6–311++G (d,p) method as well as QTAIM and NBO analyses were used to the acidity values of D-GlcN and GlcNAc sugars and their complexes with alkali ions in the gas phase. The Li+, Na+ and K+ prefer bi-dentate chelate in these complexes. The computed results indicate that metal ion affinity (MIA) in GlcNAc is higher than that in D-GlcN. There are direct correlations between the MIA values of D-GlcN and GlcNAc sugars and the atomic numbers of Li, Na, and K. The calculated acidity values for GlcNAc at C 2 –NH and C 6 –HO 6 sites are 331 and 333 kcal mol−1, respectively. Whereas the calculated acidity values for D-GlcN at C 2 –NH and C 6 –HO 6 sites are 365 and 372 kcal mol−1, respectively. The AIM and NBO analyses indicate the presence of intramolecular H-bonds in GlcNAc sugar in both its neutral form and conjugate base; whereas D-GlcN indicates intramolecular H-bonds in only its conjugate base. Image 1 • Hydrogen bonding effect on Acidity of d -Glucosamine and N-Acetyl- d -Glucosamine. • Metal Ion Affinity of d -Glucosamine and N-Acetyl- d -Glucosamine. • D-Glucosamine and N-acetyl-D-glucosamine as ideal cation exchangers models. [ABSTRACT FROM AUTHOR]

In this article, we report the computational examination of the impact of hydrogen bonding (HB) on the stereoselectivity of a series of Diels–Alder (DA) reactions. Four different types of diene/dienophile couples were studied including (a) cyclopenta-2,4-dien-1-ol and heteroatom-substituted cyclopentenes, (b) substituted cyclopentadienes and N-protonated 2,5-dihydro-1H-pyrrole, (c) furan and N-protonated 5-azabicyclo[2.1.1]hex-2-ene, and (d) N-protonated cyclopenta-2,4-dien-1-amine and α,β-unsaturated carbonyl compounds. These systems were designed such that the HB can only exist in the exo reaction pathway. The optimized structures of the transition states (TSs) and products, along with the Gibbs free energies of activation and reaction were calculated in the gas phase and dichloromethane by B3LYP/6-31G++(d,p) method. It was found that the exo adduct is the most kinetically and thermodynamically favored product for all of the DA reactions mentioned above. Moreover, the role of the HB in stabilizing the exo stereoisomer (and the corresponding TS) was much more pronounced for the reactions involving cationic species (cases b–d). In the end, a hypothetical synthetic method was proposed for obtaining exo-2-alkylbicyclo[2.2.1]heptanes. Our findings suggest that the HB can be employed as an effective interaction to control the stereoselectivity of DA reactions. [ABSTRACT FROM AUTHOR]

In this study, the effects of the remote intramolecular hydrogen bonding on the acidity of hydroxy‐1,4‐benzoquinone derivatives have been investigated ab initio by employing density functional theory (DFT) methods. The computational studies were performed for both gas and solution (H2O, DMSO, and MeCN solutions) phases. Our results indicated that remote hydrogen bonding could play an important role in increasing the acidity of hydroxy‐1,4‐benzoquinone. Noncovalent interaction reduced density gradient (NCI‐RDG) methods were used to visualize the attractive and repulsive interactions in the studied acids and their conjugate bases. Natural bond orbital (NBO) analysis was performed to confirm intramolecular hydrogen bonding effect on acidity. Quantum theory of atoms in molecules (QTAIM) was also used to study the nature of hydrogen bonds. QTAIM results showed that the intramolecular hydrogen bonds in these structures are electrostatic (closed‐shell) interactions in nature. In this study, the effects of the remote intramolecular hydrogen bonding on the acidity of hydroxy‐1,4‐benzoquinone derivatives are explored by using ab initio and density functional theory (DFT) calculations. It was found that remote hydrogen bonding could play a surprisingly role in increasing the acidity of hydroxy‐1,4‐benzoquinone. [ABSTRACT FROM AUTHOR]