Relative Stability Of Conformers Research Articles

Exploring the conformational landscape, hydrogen bonding, and internal dynamics in the diallyl ether and diallyl sulfide monohydrates.

The conformational spaces of the diallyl ether (DAE) and diallyl sulfide (DAS) monohydrates were explored using rotational spectroscopy from 6 to 19GHz. Calculations at the B3LYP-D3(BJ)/aug-cc-pVTZ level suggested significant differences in their conformational behavior, with DAE-w exhibiting 22 unique conformers and DAS-w featuring three stable structures within 6 kJ mol-1. However, only transitions from the lowest energy conformer of each were experimentally observed. Spectral analysis confirmed that binding with water does not alter the conformational preference for the lowest energy structure of the monomers, but it does influence the relative stabilities of all other conformers, particularly in the case of DAE. Non-covalent interaction and quantum theory of atoms in molecules analyses showed that the observed conformer for each complex is stabilized by two intermolecular hydrogen bonds (HBs), where water primarily interacts with the central oxygen or sulfur atom of the diallyl compounds, along with secondary interactions involving the allyl groups. The nature of these interactions was further elucidated using symmetry-adapted perturbation theory, which suggests that the primary HB interaction with S in DAS is weaker and more dispersive in nature compared to the primary HB in DAE. This supports the experimental observation of a tunneling splitting exclusively in the rotational spectrum of DAS-w, as the weaker contact allows water to undergo internal motions within the complex, as shown based on calculated transition state structures for possible tunneling pathways.

DFT study, and natural bond orbital (NBO) population analysis of 2-(2-Hydroxyphenyl)-1-azaazulene tautomers and their mercapto analouges

Theoretical research on the keto-enol tautomerization of 2-(2-Hydroxyphenyl)-1-aza azulene (2HPhAZ) and its thiol-thione (2MPhAZ) analouge has been performed using the density functional B3LYP method with the 6–311 + + G(2d,2p) basis set in gas and ethanol phases. The findings of the MO computation on the energy scale and the prediction of the frontier molecular orbital (FMO) energies demonstrate that the tautomeric structures exist in a static mixture in the ground state, with the enol and thiol structure being more stable than the keto and thione structures in gas phase. The ethanol solvent causes some reordering of the relative stability of 2HPhAZ and 2MPhAZ conformers. The geometries created at the B3LYP/6–311 + + G(2d,2p) level of theory were used for NBO analysis. In the tautomerization of 2HPhAZ and its mercapto analogue 2-(2-Mercaptophenyl)-1-azaazulene (2MPhAZ), it has been found that the O(S)-C sigma bond is weak due to nO(S)—> σ*C25-O26(S26) and nO(S)—> σ*C15-N16 delocalization. It is also noted that the resulting p character of the corresponding oxygen (sulfur) natural hybrid orbital (NHO) of σO(S)-C bond orbital is related to the decreased occupancy of the localized σO(S)-C orbital in the idealized Lewis structure or the increased occupancy of σ*O(S)-C of the non-Lewis orbital and their subsequent impact on molecular stability and geometry (bond lengths) in gas phase and ethanol. Additionally, the energy of charge transfer decreases as the potential rotamers' Hammett constants (R1–R3 for O(S) atoms) increase. The partial charge distribution on the skeleton atoms demonstrates that the intra- and intermolecular interactions can be significantly influenced by the electrostatic attraction or repulsion between atoms. Lastly, the currently applied NBO-based HB strength indicator enables a fair prediction of the frequency of the proton donor NH stretching mode, but this simple picture is hidden by abundant hype conjugative effects.

Exploring Kinase Asp-Phe-Gly (DFG) Loop Conformational Stability with AlphaFold2-RAVE.

Kinases compose one of the largest fractions of the human proteome, and their misfunction is implicated in many diseases, in particular, cancers. The ubiquitousness and structural similarities of kinases make specific and effective drug design difficult. In particular, conformational variability due to the evolutionarily conserved Asp-Phe-Gly (DFG) motif adopting in and out conformations and the relative stabilities thereof are key in structure-based drug design for ATP competitive drugs. These relative conformational stabilities are extremely sensitive to small changes in sequence and provide an important problem for sampling method development. Since the invention of AlphaFold2, the world of structure-based drug design has noticeably changed. In spite of it being limited to crystal-like structure prediction, several methods have also leveraged its underlying architecture to improve dynamics and enhanced sampling of conformational ensembles, including AlphaFold2-RAVE. Here, we extend AlphaFold2-RAVE and apply it to a set of kinases: the wild type DDR1 sequence and three mutants with single point mutations that are known to behave drastically differently. We show that AlphaFold2-RAVE is able to efficiently recover the changes in relative stability using transferable learned order parameters and potentials, thereby supplementing AlphaFold2 as a tool for exploration of Boltzmann-weighted protein conformations (Meller, A.; Bhakat, S.; Solieva, S.; Bowman, G. R. Accelerating Cryptic Pocket Discovery Using AlphaFold. J. Chem. Theory Comput. 2023, 19, 4355-4363).

Effects of Gamma Radiation on Single- and Multicomponent Organic Crystalline Materials.

Exploration of highly ionizing radiation damage to organic materials has mainly been limited to polymers and single-component organic crystals due to their use in coatings and scintillation detection. Additional efforts are needed to create new tunable organic systems with stability in highly ionizing radiation to rationally design novel materials with controllable chemical and physical properties. Cocrystals are a promising class of compounds in this area because of the ability to rationally design bonding and molecular interactions that could lead to novel material properties. However, currently it is unclear if cocrystals exposed to radiation will maintain crystallinity, stability, and physical properties. Herein, we report the effects of γ radiation on both single-component- and multicrystalline organic materials. After irradiation with 11 kGy dose both single- (trans-stilbene, trans-1,2-bis(4-pyridyl)ethylene (4,4'-bpe), 1,n-diiodotetrafluorobenzene (1,n-C6I2F4 ), 1,n-dibromotetrafluorobenzene (1,n-C6Br2F4 ), 1,n-dihydroxybenzene (1,n-C6H6O2 ) (where n = 1, 2, or 3)), and multicomponent materials (4,4'-bpe)·(1,n-C6I2F4 ), (4,4'-bpe)·(1,n-C6Br2F4 ), and (4,4'-bpe)·(1,n-C6H6O2 ) were analyzed and compared to their preirradiated forms. Radiation damage was evaluated via single-crystal- and powder-X-ray diffraction, Raman spectroscopy, differential scanning calorimetry, and solid-state fluorimetry. Single-crystal X-ray diffraction analysis indicated minimal changes in the lattice postirradiation, but additional crystallinity changes for bulk materials were observed via powder X-ray diffraction. Overall, cocrystalline forms with 4,4'-bpe were more stable than the related single-component systems and were related to the relative stability of the individual conformers to γ radiation. Fluorescence signals were maintained for trans-stilbene and 4,4'-bpe, but quenching of the signal was observed for the cocrystalline forms to varying degrees. Three of the single components, 1,2-diiodotetrafluorobenzene (1,2-C6I2F4 ), 1,4-diiodotetrafluorobenzene (1,4-C6I2F4 ), and 1,4-dibromotetrafluorobenzene (1,4-C6Br2F4 ), also underwent sublimation within an hour of exposure to air postirradiation. Further analysis using differential scanning calorimetry (DSC) and Raman spectroscopy attributed this phenomenon to removal of impurities adsorbed to the crystal surface during irradiation.

Understanding the mechanism of the sulfur mustard hydrolysis reaction on the atomistic level from experiment and first-principles simulations

After World War II, the Baltic Sea was contaminated by dumping unused sulfur mustard (SM) and other chemical warfare agents (CWAs), which now constitutes a huge environmental hazard. We use both experimental and theoretical methods to understand the reactivity of SM in water, in particular the hydrolysis, which is one of the chemical reactions leading to the neutralization of SM. Real conditions present in the Baltic Sea are represented by performing Car-Parrinello molecular dynamics simulations for sulfur mustard in explicit water solution at finite temperature. We study the relative occurrence and stability of various SM conformers in water and analyze the solute–solvent interactions, with special focus on the formation of intra- and intermolecular hydrogen bonds and their lifetime. A missing piece toward the understanding of the sulfonium cation formation and SM hydrolysis reaction is provided by obtaining the activation energy for SM decomposition in water solution from gas chromatography–mass spectrometry (GC-MS) experiments. The complex mechanism of SM hydrolysis is also studied by umbrella sampling simulations to obtain the free energy barrier for the sulfonium cation formation and to provide an atomistic view of the reaction process.

Importance of Solvent-Bridged Structures of Fluorinated Diphenylalanines: Synthesis, Detailed NMR Analysis, and Rotational Profiles of Phe(2-F)-Phe(2-F), Phe(2-F)-Phe, and Phe-Phe(2-F).

The crystal structure of l-phenylalanyl l-phenylalanine (Phe-Phe, FF, a.k.a. diphenylalanine) is not merely noncentrosymmetric, but it is highly dipole parallel aligned. It is for this reason that FF is a nonlinear optical (NLO) material and exhibits strong second harmonic generation (SHG). Enhancement of the SHG response by ortho fluorination was demonstrated. Crystallization is nontrivial, and learning about the zwitterion structures in solution is important for the rational improvement of the crystallization process. Here, we present an NMR study of di-fluorinated FF (Phe(2-F)-Phe(2-F)) and mono-fluorinated FF isomers (Phe(2-F)-Phe and Phe-Phe(2-F)). The dipeptides were prepared by solid-phase synthesis and purified by high-performance liquid chromatography (HPLC). Their 1H and 13C NMR spectra were recorded in partially deuterated water (10% D2O), and two-dimensional (2D) NMR techniques were employed for signal assignments. The unambiguous assignments are reported of all chemical shifts for the aliphatic H and C atoms and of the C atoms of the carboxylate, the amide carbonyl, the CF carbons, and of every arene C atom in each phenyl ring. The dipeptides are trans amides and intramolecular hydrogen bonding between the ammonium group and the amide carbonyl restricts the H3N-CH-C(O) geometry. We explored the rotational profile of the diphenylalanines as a function of the τ = ∠(C-N-C-CO2) dihedral angle at the SMD(B3LYP/6-31G*) level without and with specific hydration and report the associated Karplus curves J(θ) vs θ = ∠(H-N-C-H). The rotational profiles show a maximum of three stationary structures, and relative conformer stabilities of the free diphenylalanines show that the conformation found in the crystal M1 is the least stable among the three, M3 > M2 ≫ M1. Specific water solvation makes all of the difference and adds a large competitive advantage to the water-bridged ion pair M1a. In fact, M1a becomes the most stable and dominant conformation for the parent diphenylalanine and mono1 F-FF and M1a becomes competitive with M3c for mono2 F-FF and di F-FF. Implications are discussed regarding the importance of the conformational preorganization of diphenylalanines in solution and the facility for their crystallization.

An MP2/Molecular Dynamics study of the solvent effects on the conformational equilibrium of the glycine dipeptide

The solvent effects on the conformational equilibrium of the Glycine dipeptide are studied using a Quantum Mechanics/Molecular Mechanics method based on the mean field approximation. Glycine is the structurally simplest amino acid found in nature and is usually considered the amino acid that best conforms to the basic assumptions of the random coil model. It has been experimentally found, however, that in gas phase the conformational landscape of the glycine dipeptide is dominated by only two structures (C5 and C7) characterized by the formation of an intramolecular hydrogen bond (HB). In this work we show that a similar situation is found in water solution: the conformational equilibrium is also dominated by only two structures (PPII and α) that, furthermore, are not stable in gas phase and in which the intramolecular HB is replaced by an intermolecular HB. This behavior mimics that of other peptides which display less conformational freedom. We show that relative stability results from the interplay of two free energy components that operate in opposite directions: internal energy and dipeptide-water interaction energy. The influence exerted by the solvent structure and the dipeptide charge distribution on the relative stability of the different conformers is also analyzed.

Direct orbital selection within the domain-based local pair natural orbital coupled-cluster method.

Domain-based local pair natural orbital coupled cluster (DLPNO-CC) has become increasingly popular to calculate relative energies (e.g., reaction energies and reaction barriers). It can be applied within a multi-level DLPNO-CC-in-DLPNO-CC ansatz to reduce the computational cost and focus the available computational resources on a specific subset of the occupied orbitals. We demonstrate how this multi-level DLPNO-CC ansatz can be combined with our direct orbital selection (DOS) approach [M. Bensberg and J. Neugebauer, J. Chem. Phys. 150, 214106 (2019)] to automatically select orbital sets for any multi-level calculation. We find that the parameters for the DOS procedure can be chosen conservatively such that they are transferable between reactions. The resulting automatic multi-level DLPNO-CC method requires no user input and is extremely robust and accurate. The computational cost is easily reduced by a factor of 3 without sacrificing accuracy. We demonstrate the accuracy of the method for a total of 61 reactions containing up to 174 atoms and use it to predict the relative stability of conformers of a Ru-based catalyst.

Conformational Change in Molecular Crystals: Impact of Solvate Formation and Importance of Conformational Free Energies

Changes in molecular conformation and its relationship with crystal polymorphism have been well documented in previous work. To the best of our knowledge, however, the effect of solvate formation on molecular conformation has never been explored. Using the Cambridge Structural Database in combination with molecular modeling, we provide insights into the impact of solvate formation on the conformation adopted by a compound and whether such conformation is different to that found in its neat form(s). Typically, the more flexible a molecule is, the higher the chances that conformational change occurs upon solvate formation. There are no trends as to the relative stability of conformers and their likelihood to be observed in either the solvates or the neat forms. Typically, conformer energy differences in solvate-neat form pairs are small (<5 kJ/mol) and when larger energy differences are observed (>15 kJ/mol), these can be reduced significantly when both solvent and thermal effects are considered in the simulations. This highlights of the importance of computing thermal contributions in conformer energies as well as accounting for environmental effects. Overall, we find that conformational change in solvate-neat form pairs mirrors the behavior of conformational change in polymorphism.

New promising generation of phosphates α-aminophosphonates: Design, synthesis, in-vitro biological evaluation and computational study

A novel category of phosphate-phosphonate compounds is synthesized by a sequence multicomponent reactions strategy of Kabachnik-Fields and Atherton-Todd reactions. All the designed products are obtained with good chemical yields in short reaction times, and confirmed by spectroscopy analyses. The diethyl [(4-diethylphosphate phenyl) (4-trifluoromethyl phenylamino) methyl] phosphonate 6g is characterized by single-crystal X-ray analysis. These compounds exhibited a strong antifungal effect, a low inhibition of AChE, and no inhibitory activity on BChE, with interesting antioxidant capacity. Results make them promising candidates as original organophosphorus pesticides. The DFT calculations concerning relative stability of various conformers, besides the comparison of the measured and calculated NMR spectra of selected compounds; suggest that conformational interconversion can quite easily occur in this type of molecules, so that many structures of the same compound can coexist in solution.

STRUCTURAL ANALYSIS OF PLASMID-MEDIATED VEROTOXIN GENE PRODUCING NON-O157 ESCHERICHIA COLI USING MOLECULAR DYNAMIC SIMULATIONS

Plasmid-mediated Non-O157 VTEC is a pathogenic E. coli serotype, are responsible for many life-threatening diseases such as diarrhoea. The thermostable crystal structure has been widely sought after for industry and therapeutic applications through the structural analysis. The National Center for Biotechnology Information (NCBI) Genbank Database has been sourced to obtain plasmid-mediated Verotoxin genes producing non-O157 MN 696158 (Vtx1-1) and MN688720 (Vtx2) sequences. The tertiary structure of MN696158 (Vtx1-1) and MN688720 (Vtx2) was generated by operating MODELLER. The result exposed multiple templates during modelling processes have improved the local stereochemical quality of the produced models. The structural analysis also disclosed the similarities and differences between the models (Vtx1-1 and Vtx2). Furthermore, the thermal stability profile of plasmid-mediated non-O157 VTEC were studied. The molecular dynamics simulations of plasmid-mediated non-O157 VTEC structures (Vtx1-1 and Vtx2) illustrated the interactions between amino acids. On the other hand, Vtx1-1 and Vtx2 showed noticeable differences in their relative conformational flexibility and stability at elevated temperature. However, it is expected that the information of the thermal stable of plasmid-mediated non-O157 VTEC models can be used for potential vaccine candidate through protein engineering in future.

Lactic Acid Spectroscopy: Intra- and Intermolecular Interactions.

Lactic acid, a relevant molecule in biology and the environment, is an α-hydroxy acid with a high propensity to form hydrogen bonds, both internally and to other hydrogen-bond-accepting molecules. This work includes the novel recording of infrared spectra of gas-phase lactic acid using Fourier transform infrared spectroscopy, and the vibrational absorption features of lactic acid are assigned with the aid of computationally simulated vibrational spectra with anharmonic corrections. Theoretical chemistry methods are used to relate intramolecular hydrogen-bond strengths to the relative stability of lactic acid conformers. The formation of hydrogen-bonded lactic acid dimers and 1:1 water complexes is investigated by simulated vibrational spectra and calculated thermodynamic parameters for the lactic acid monomer and dimer and its water complex in the gas phase. The results of this study are discussed in the context of environmental chemistry with an emphasis on indoor environments.

Metal–Organic Frameworks: On the Role of Enthalpic and Entropic Contributions to the Conformational Free Energy Landscape of MIL‐101(Cr) Secondary Building Units (Adv. Theory Simul. 12/2020)

A major cause of defects during the synthesis of metal–organic frameworks (MOFs) is the thermostructural behavior of the precursors used. In article number 2000092, Vassiliki-Alexandra Glezakou, Matteo Salvalaglio, and co-workers use enhanced sampling methods to evaluate the flexibility of MIL-101(Cr) half-secondary building units (SBUs) in solution. They find that the interplay between enthalpy and entropy determines the most probable conformational state for such precursors, highlighting the importance of explicitly considering entropic effects when estimating the relative stability of different conformers of SBUs.

On the Role of Enthalpic and Entropic Contributions to the Conformational Free Energy Landscape of MIL‐101(Cr) Secondary Building Units

AbstractThe thermo‐structural behavior of metal‐organic framework (MOF) precursors is responsible for regulating the introduction of defects in MOF structures during synthesis. In this paper, factors affecting the flexibility of MIL‐101(Cr) half‐secondary building units (half‐SBUs) are evaluated in solution using enhanced sampling methods. In particular, entropic and enthalpic contributions to the conformational free energy landscape of isolated MIL‐101(Cr) half‐SBUs are calculated in water, in the presence and absence of ionic species (Na+ and F−), and in N, N‐dimethylformamide (DMF). This analysis leads to the observation that the interplay between enthalpy and entropy determines the most probable conformational state for half‐SBUs. This observation extends to the most relevant SBU intermediate, in which conformational entropy plays a key role in stabilizing configurations that differ from those found in the MIL‐101(Cr) crystal structure. The findings highlight the importance of explicitly considering entropic effects, associated with finite‐temperature sampling when estimating the relative stability of different conformers of SBUs.

Adsorption of sulfur mustard on clean and water-saturated ZnO(10[formula omitted]0): Structural diversity from first-principles calculations

We investigate the adsorption of a chemical warfare agent, namely sulfur mustard (SM), on clean and water-saturated ZnO(101¯0) surfaces using density functional theory calculations to understand the first step of its efficient neutralization to less toxic chemical compounds. We determine the relative stability of various SM conformers adsorbed at different sites on both ZnO surfaces. The unique hydrogen bonding patterns obtained for the idealized clean and the more realistic water-saturated ZnO surface are analyzed and their influence on the stability of the SM@ZnO structures is demonstrated. We find that absolute values of the calculated binding and interaction energies are significantly higher for the clean than for the water-saturated ZnO surface due to the formation of Cl⋯Zn and S⋯Zn contacts. The high adsorptive reactivity of the clean ZnO surface is also evident from the strong structural changes of the initial local energy minimum gas-phase conformations of the SM molecules upon adsorption. This phenomenon is not observed for the water-saturated ZnO surface, which has almost no impact on the SM conformation after adsorption, leaving it as it exists in the gas phase. The insights from the results obtained provide a missing piece toward the understanding of the complex mechanism of SM neutralization on ZnO surfaces.

Computational simulation of anion binding association mechanisms contributing toward rotation of pyrrole rings in dipyrrolyldiketone BF2 complexes.

Dipyrrolyldiketone BF2 complexes have a characteristic association mechanism with anions; an anion is tightly captured by the NH bonding of the two rotated pyrrole rings and the CH bonding of the backbone in dipyrrolyldiketone BF2 complexes. In order to elucidate this anion association mechanism in dipyrrolyldiketone BF2 complexes, the relative stability of several conformers of the dipyrrolyldiketone BF2 complex and anion complexes are initially calculated by quantum mechanical density functional theory (DFT). Second, molecular dynamics (MD) simulations were performed for systems comprising a dipyrrolyldiketone BF2 complex and Cl− with several types of countercations in CH2Cl2. From our DFT calculations, it was observed that isomerization could be classified by whether Cl− changes its position relative to the dipyrrolyldiketone BF2 complex or not. From the MD simulations, we found the size effect of countercations: a large cation is released from dipyrrolyldiketone BF2 complexes more frequently than smaller cations. Meanwhile, when Na+ is employed as the cation, the formation of a seven-membered ring-like cluster suppresses both the isomerizations. Furthermore, MD simulations suggest that the presence of an anion is critical to stabilize the two rotated pyrrole rings. Hence, from our MD simulations, we have clearly found that the size of the cation affects the isomerization processes.

Relative Stability of Digermane Conformers in Nanotubes

Relative stability of the staggered and eclipsed forms of digermane in model single-walled carbon nanotubes has been simulated by means of the PBE/3ζ DFT approximation. It has been shown that the influence of the nanosystem force field on the encapsulated molecule leads to a change in the length of the Ge—Ge bonds and partial charges on the atoms, the formation of a negative electric charge on Ge2H6 molecule and, as a result, to an increase in the relative stability of the eclipsed form for the endo complexes with relatively small nanotube diameter.

Conformational design concepts for anions in ionic liquids.

The identification of specific design concepts for the in silico design of ionic liquids (ILs) has been accomplished using theoretical methods. Molecular building blocks, such as interchangeable functional groups, are used to design a priori new ILs which have subsequently been experimentally investigated. The conformational design concepts are developed by separately and systematically changing the central (imide), bridging (sulfonyl) and end (trifluoromethyl) group of the bis(trifluoromethanesulfonyl)imide [N(Tf)2]− anion and examining the resultant potential energy surfaces. It is shown that these design concepts can be used to tune separately the minimum energy geometry, transition state barrier height and relative stability of different conformers. The insights obtained have been used to design two novel anions for ILs, trifluoroacetyl(methylsulfonyl)imide [N(Ms)(TFA)]− and acetyl(trifluoromethanesulfonyl)imide [N(Tf)(Ac)]−. The computationally predicted structures show excellent agreement with experimental structures obtained from X-ray crystallography. [C4C1im][N(Tf)(Ac)] and [C4C1im][N(Ms)(TFA)] ILs have been synthesised and ion diffusion coefficients examined using pulsed field gradient stimulated echo NMR spectroscopy. Significantly increased diffusion was observed for the more flexible [N(Tf)(Ac)]− compared with the more rigid [N(Ms)(TFA)]− analogue. Furthermore, a pronounced impact on the fluidity was observed. The viscosity of the IL with the rigid anion was found to be twice as high as the viscosity of the IL with the flexible anion. The design concepts presented in this work will enable researchers in academia and industry to tailor anions to provide ILs with specific desired properties.

Combined Experimental and Theoretical Survey of the Gas-Phase Reactions of Serine-Ca2+ Adducts.

The association of Ca2+ to serine and the subsequent gas-phase unimolecular reactivity of the [Ca(Ser)]2+ (Ser = Serine) adduct was investigated throughout the use of tandem mass spectrometry techniques and B3LYP/6-311+G(3df,2p)//B3LYP/6-311+G(d,p) density functional theory calculations. In a first step, the structure and relative stability of all possible conformers of serine were obtained and analyzed, as well as the most stable [serine-Ca]2+ adducts. For the analysis of the different potential energy surfaces associated with the gas-phase unimolecular reactivity of these adducts, only those that differ by less than 100 kJ·mol-1 from the global minimum were taken into account. In agreement with previous studies, the serine-Ca2+ global minimum corresponds to a charge-solvated structure in which Ca is tricoordinated to neutral serine. The major peaks observed in the nanoelectrospray-MS/MS spectrum of [Ca(Ser)]2+ adduct correspond to both Coulomb explosions, yielding either CaOH+ + [C3,H6,N,O2]+ or [C2,H4,O,N]+ + [Ca(C,H3,O2)]+, and to the loss of neutrals, namely, CH2O and H2O. Our theoretical survey of the energy profile allow us to conclude that, although all the aforementioned fragmentation processes can have their origin at the global minimum, similar fragmentations involving low-lying conformers, both zwitterionic and nonzwitterionic, compete and should be considered to account for the observed reactivity. We have also found that in some specific cases post-transition state dynamics similar to the ones described before in the literature for formamide-Ca2+ reactions, may also play a role.

Theoretical Comparison of the Stabilities of Hoogsteen and Watson–Crick Conformations for Proton‐bound Base‐pairing of Nucleic Acid Bases and Nucleosides in the Gas Phase

Relative stabilities of proton-bound Hoogsteen and Watson-Crick conformations.