Conformational analysis of diastereomeric α-amino nitriles [1S,2R,(S)]- and [1S,2R,(R)]-N-cyanophenylmethyl-1-aminoindan-2-ol [(S)-1 and (R)-1] has been carried out at the DFT B3LYP/6-31G* level. It was found that these compounds consist of tens of conformers: There are three stable conformations S1–S3 for (S)-1 within a narrow energy window (0.4 kcal/mol) with the population being 43% (S1), 24% (S2), and 22% (S3), respectively (Table 1). On the other hand, the global minimum conformation of (R)-1 (R1) is more than 1.51 kcal/mol more stable than the other conformations and occupies 76% of the population (Table 2). The difference in the total energy between the two diastereomers is small (ΔE = –0.09 kcal/mol), which is in reasonable agreement with the fact that the two diastereomers equilibrate with a ratio of 50:50 in DMSO. On the contrary, it has been shown that (S)-1 is more stable than (R)-1 in the crystal form. The crystal-state conformation of (S)-1 (S0) determined by an X-ray crystallographic analysis agrees well with S3 (Figure 1, Table 3). In the crystals, one molecule binds to four neighboring molecules with hydrogen bonds (Figure 2b). In addition, the crystal density of (S)-1 is higher than that of (R)-1. These observations suggest that the S3 molecules are packed tightly together to form, with assistance of the intermolecular hydrogen bonds, a stable crystal. On the other hand, the crystal-state conformation of (R)-1 (R0) is different from R1 with regard to the conformation of the phenyl moiety, as well as the mode of an intramolecular hydrogen bond (Figure 1, Table 3). Taking account of the low crystal density of (R)-1, it seems that R1 is not likely to crystallize in its conformation. Therefore, the R1 molecules are assumed to change the conformation and the hydrogen-bond mode upon crystallization to narrowly form a not so stable crystal.

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Room temperature ionic liquids (RTILs) are useful as new solvents or materials owing to their favorable properties such as negligible vapor pressure, non-flammability, and wide electrochemical window. For further development of new RTILs, it is indispensable to understand macroscopic properties as solvent and/or liquids of RTILs at a molecular or atomistic level. Here, liquid structure and the ion-ion interactions of room temperature ionic liquid ethylammonium nitrate (EAN) were studied by means of large angle X-ray scattering (LAXS) experiment and molecular dynamics simulations. X-ray interference function for EAN shows a small peak of 0.62 Å^–1 indicating nano-scale segregation in the ionic liquid. X-ray radial distribution function as the form of D(r) – 4πr²ρ₀ evidently shows a peak of 3.4 and broad ones of 4.7, 8 and 12 Å, suggesting that EAN has long range ordering in the liquid state. The intra-molecular X-ray interference function was estimated on the basis of molecular geometries found in crystals to yield the inter-molecular X-ray pair correlation functionG_mathrm{inter}mathrm{LAXS}(r). In G_mathrm{inter}mathrm{LAXS}(r), peaks of 3.0, 3.4, and 4.7 Å were found as the atom-atom correlation. The peak of 3.0 Å can be assigned to the atom-atom correlation of N (C₂H₅NH₃⁺)…O (NO₃^–) in the NH…O hydrogen bonding. In addition, the peak of 3.4 Å is also ascribable to C (C₂H₅NH₃⁺)…O (NO₃^–) correlations in the CH…O interactions. Molecular dynamics simulations based on newly developed force fields to describe a series of primary ammonium cation were performed to ascribe the peaks found in G_mathrm{inter}mathrm{LAXS}(r). The X-ray interference function imathrm{MD}(s) and the pair correlation function Gmathrm{MD}(r) derived from simulations were reasonably in agreement with the experimental ones. According to the partial atom-atom correlation functions derived from the simulations, the experimentally observed peaks of 3.0 and 3.4 Å can be ascribable to the NH…O and the CH…O correlations in the closest ethylammonium and nitrate interaction, respectively. The CH…O interactions may play an important role in macroscopic properties of this kind of ionic liquids.

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For theoretical study on interesting enantiodifferenciating photoisomerization of (Z)-cyclooctene (1Z) to (E)-cyclooctene (1E) by chiral benzenepolycarboxylates (2a) in solution, the profiles of energy and stereochemical change of the sensitized photoisomerization were inferred by molecular simulation by use of MOPAC-PM5 method.
The energy, stereochemical change and equilibrium of the ground states and excited singlet states of 1Z, 1E, tetramethyl 1,2,4,5-benzenetetracarboxylate (2b), dimethyl 3,5-bis(trifluoromethyl)benzoate (2c), and (R)- and (S)-dimenthyl 3,5-bis(trifluoromethyl)benzoate (2dr and 2ds) as a chiral model of 2a were first interpreted. 1Z has an asymmetric conformer and the isomerization to (R)- or (S)-1E may be dependent on preferential one-side rotation. Inferred exciplexes (Ex1) such as 1Z·2b^* (2b^*: excited singlet state of 2b) occur via energy transfers through some interactions to bring the next loose exciplexes (Ex2) such as 1E^*·2b, which give 1E at the respective 1E/1Z ratio. The Ex1 and Ex2 structures were inferred to possess proper π^*/π and C-H/π interactions, ester C=O/HC (olefin and allyl) and F/H hydrogen bondings, placed in parallel or alongside depending on the substituents. The photoisomerization may depend on the energy difference between the two exciplexes, and the transition state (TS) energy. The carbonyl groups and π components on the enantiomeric polycarboxylates make selective hydrogen bondings, π^*/π and CH/π interactions with the olefin and allyl groups on asymmetric 1Z, and bring diastereomeric Ex1. Those interaction accumulations are inferred to bring enantiodifferentiating energy transfer by one-side rotation (asymmetric environment) of the two molecules for (R)-1E or (S)-1E like enzymes.

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Firefly luciferase is a well-known enzyme that participates in the bioluminescence reaction. Recently, it was reported that this enzyme also exhibits enantioselective thioester formation activity of 2-arylpropanoic acid such as ketoprofen. However, the enantiodifferential mechanism was still unknown. Therefore to clarify the reason of enantioselective thioester formation toward ketoprofen, we have performed molecular dynamics (MD) simulations for three kinds of firefly luciferase / acyl-AMP intermediate analogue complexes. Targeted substrates were N-acylsulfamate derivatives of R-ketoprofen, S-ketoprofen and 3-benzoylphenylacetic acids. Our results show that the dynamic behavior of Ser200 and Ser201 around the asymmetric carbon atom in the complexes is quite different.

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In order to explore the possible polymorphs of aspirin crystal recently discovered in the subtle crystal packing form, conformational analysis of aspirin monomer and conformational polymorphism analysis of aspirin crystal were carried out using CONFLEX/KESSHOU (CONFLEX/K) which have implemented all functions of our crystal calculation program KESSHOU into our molecular mechanics program CONFLEX having an efficient conformational space search method. Ten conformers found by the exhaustive conformation search of a monomeric aspirin molecule (isolated in vacuum) were subjected to geometry optimizations and normal mode analyses using MMFF94 and ab initio (MP2/6-31+G**) calculations, and then, we examined the energy minima on the MMFF94 and MP2 potential energy surface, respectively. On the MM3 potential energy surface, nine conformers were also confirmed (energy minima), although one conformation was merged into another minimum by the geometry optimization. In comparison with the known aspirin conformations reported by Glaser, CONFLEX conformation search missed one of his conformations, but it is not an energy minimum of MMFF94 and MM3. To examine the accuracy of our CONFLEX/K crystal calculation, both known X-ray crystal forms of aspirin were subjected to crystal lattice optimization (LOPT) method by using MMFF94 and MM3 for intermolecular potential. It is surprisingly noted that MM3 can almost completely represent the observed crystal structures. In order to analyze the conformational polymorphism of aspirin crystal, twenty and eighteen trial crystal structures were generated by using ten MMFF94 and nine MM3 conformers, respectively, and applying form I and form II crystal structure information, and were optimized by LOPT optimizations with the corresponding force field. The results showed that 2SSc/I and 2SSc/II are the most stable crystal structures in both force fields and were in good agreement with the experimental crystal structures. The tautomeric conformational polymorphs, 1SAc/I and 1SAc/II, which can be formed from 2SSc/I and 2SSc/II, respectively, by proton exchange between the carboxylic groups of centrosymmetric aspirin dimer in the crystal, were also evaluated as stable crystal structures with both MMFF and MM3 intermolecular potential. On the other hand, the other conformational polymorphs have higher crystal energies than 10 kcal/mol from the lowest energy polymorph 2SSc/II. Therefore, we concluded that, except for two known polymorphs and their tautomers, there are extremely low probabilities for the existence of the artificial conformational polymorphs, at least, that we examined here.

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Density functional calculations were carried out on some reaction center models of horse heart carbonmonoxy myoglobin (MbCO) to investigate, from a quantum chemical perspective, the relationship between the heme-ligand moiety and the imidazole hydrogen in the distal histidine. Compared to the δ positioned model, the ε positioned one, in which the hydrogen is close to the carbonyl (CO) ligand, produced positive electrostatic potential around the heme Fe-CO moiety, and stabilized the energy levels of the highest occupied states originated in heme Fe. The difference in the hydrogen position also influenced the CO, and the amount of the difference in Mulliken charge on the CO carbon was 0.016. The interaction between the distal histidine and heme-ligand in MbCO was remarkable, and it was suggested that quantum chemical study to take distal histidine into consideration is indispensable in the representation of the electronic structure of the MbCO reaction center.

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