Absolute Configuration Determination of Chiral API Molecules by MicroED Analysis of Cocrystal Powders Formed Based on Cocrystal Propensity Prediction Calculations.

Establishing the absolute configuration of chiral active pharmaceutical ingredients (APIs) is of great importance. Single crystal X-ray diffraction (scXRD) has traditionally been the method of choice for such analysis, but scXRD requires the growth of large crystals, which can be challenging. Here, we present a method for determining absolute configuration that does not rely on the growth of large crystals. By examining microcrystals formed with chiral probes (small chiral compounds such as amino acids), absolute configuration can be unambiguously determined by microcrystal electron diffraction (MicroED). Our streamlined method employs three steps: (1) virtual screening to identify promising chiral probes, (2) experimental cocrystal screening and (3) structure determination by MicroED and absolute configuration assignment. We successfully applied this method to analyze two chiral API molecules currently on the market for which scXRD was not used to determine absolute configuration.

Quantum dynamics studies of isotope effects in the Mg+(3p) + HD → MgH+/MgD+ + D/H insertion reaction.

The time-dependent wave packet quantum dynamics studies for the Mg+(3p) + HD → MgH+/MgD+ + D/H diabatic reaction are carried out for the first time on recently developed diabatic YHWCH potential energy surfaces [Phys. Chem. Chem. Phys., 2018, 20, 6638-6647]. The results of reaction probabilities and total integral cross sections show a dramatic preference to the formation of MgD+ over MgH+ owing to the insertion reaction mechanism in the title reaction. The MgD+/MgH+ branching ratio witnesses a monotonic decrease from 10.58 to 3.88 at collision energy range of 0.01 to 0.20 eV, and at the collision energy of 0.114 eV, it is close to the experimental value of 5. The rovibrational state-resolved ICSs of the two channels show the products MgD+ have higher vibrational excitation and hotter rotational state distributions. The opacity function P(J) suggests that the MgH+ + D channel and MgD+ + H channel are dominated by high-b and low-b collisions, respectively. Both forward and backward scattering peaks are found in the differential cross section curves, whereas the angle distributions of products are not strictly forward-backward symmetric because of the short lifetime of the complex in the reaction.

Neural network potential energy surface and dynamical isotope effects for the N+(3P) + H2→ NH+ + H reaction.

The N+(3P) + H2(X1Σ) → NH+(X2Π) + H(2S) reaction is important for initiating the chain reaction of ammonia synthesis in the universe. To study the dynamics of this reaction, a global accurate potential energy surface (PES) of the ground state NH was constructed by combining numerous high-level ab initio energy points with the permutation invariant polynomial neural network method. Utilizing this newly constructed PES, time-dependent wave packet calculations were performed on the state-to-state reactions of N+(3P0) + H2 (v = 0, j = 0) and N+(3P0) + D2 (v = 0, j = 0) in order to study the microscopic reaction mechanisms and dynamical isotope effects. Isotope effects have a significant influence on the rovibrational state distributions and state resolved angle distributions of the product. The total differential cross sections (DCSs) present in the aforementioned reactions are dominated by both forward and backward scattering, as expected from the observable deep well along the reaction path. Meanwhile, the rovibrational state-resolved DCSs show that both reactions are not entirely statistical at the state-to-state level.

New diabatic potential energy surfaces of the NaH2 system and dynamics studies for the Na(3p) + H2 → NaH + H reaction.

The Na(3p) + H2(X1Σg+) → NaH(X1Σ+) + H(2S) reaction plays an important role in the field of diabatic reaction dynamics. A set of new diabatic potential energy surfaces (PESs) of the NaH2 system are structured, which include the diabatic coupling between the lowest two adiabatic states. The electronic structure calculations are performed on the multi-reference configuration interaction level with the cc-pwCVQZ and aug-cc-PVQZ basis sets for Na and H atoms. 32402 geometries are chosen to construct the diabatic data by a unitary transformation based on the molecular property method. The diabatic matrix elements of [Formula: see text], [Formula: see text] and [Formula: see text] ([Formula: see text]) are fitted by the artificial neural network model. The spectroscopic constants of diatoms obtained from the present PESs are consistent with the experimental data. The topographical and intersection characteristics of the [Formula: see text] and [Formula: see text] surfaces are discussed. Based on the new PESs, the time-dependent quantum wave packet calculations are carried out to study the reaction mechanism of the title reaction in detail.

Significant effects of vibrational excitation of reactant in K + H2 → H + KH reaction based on a new neural network potential energy surface.

The study of K + H2 collision has a long experimental history, but there have been few theoretical studies due to lack of a global potential energy surface (PES). In this study, a new global PES for the ground state of KH2 system was constructed based on numerous ab initio points, using the permutation invariant polynomial neural network method. The root mean square error (RMSE) of PES is very small (5.64 meV). On the new PES, time-dependent quantum wave packet (TDWP) and quasiclassical trajectory (QCT) calculations were carried out to study the dynamics of the K(2S) + H2(X1Σ+g) → H(2S) + KH(X1Σ+) reaction. Dynamics results show that (i) the K + H2(v = 0) → H + KH reaction scarcely occurred, (ii) the K + H2(v = 1) → H + KH reaction took place in small quantities, and (iii) the K + H2(v = 2) → H + KH reaction occurred in large quantities. This indicates that vibrational energy of the reactant is significantly more effective at promoting the reaction than the translational energy. This characteristic stems from a major physical model in reactive collisions: the vibrationally excited H2 molecule and K atom collide first in a T-geometric configuration and the vibrational motion of the H2 molecule helps separate the two H atoms a large distance after the collision. At a large H-H distance, a broad well exists on the PES, so the heavy K atom could pull back the light H atom to initiate the reaction. Similar to the reactive channel, vibrational excitation of the reactant also has a significant effect on the collision-induced dissociation channel.

Diabatic potential energy surfaces of MgH2+ and dynamic studies for the Mg+(3p) + H2 → MgH+ + H reaction.

The global diabatic potential energy surfaces (PESs) of the MgH2+ system, which can be used to study the dynamics of the Mg+(3p2P) + H2(X1Σ) → MgH+(X1Σ+) + H(2S) reaction, are structured for the first time. The diabatic PESs are correlated with the ground state 12A' and the first excited state 22A'. The multi-reference configuration interaction method and the VQZ basis set are used in ab initio calculations, and diabatic potential energies are calculated based on the molecular properties of the dipole moment. The neural network method is applied to fit the matrix elements of the diabatic energy surfaces. Spectroscopic constants of H2(X1Σg+) and MgH+(X1Σ+) obtained from the new PESs agree well with the experimental data. Based on the diabatic PESs of MgH2+, the time-dependent wavepacket calculations for the Mg+(3p2P) + H2(X1Σg+) → MgH+(X1Σ+) + H(2S) reaction are carried out to study the reaction dynamics. There is no threshold for this reaction because of the existence of barrierless reactive paths. The reaction has a high total integral cross section (ICS), and vibrationally resolved ICSs show an obvious population inversion of product vibrational states. The results of differential cross sections (DCSs) indicate that most product molecules tend to forward scatter.

Global diabatic potential energy surfaces for the BeH2 + system and dynamics studies on the Be+(2P) + H2(X1Σg +) → BeH+(X1Σ+) + H(2S) reaction.

The Be+(2P) + H2(X1Σg +) → BeH+(X1Σ+) + H(2S) reaction has great significance for studying diabatic processes and ultracold chemistry. The first global diabatic potential energy surfaces (PESs) which are correlated with the lowest two adiabatic states 12A' and 22A' of the BeH2 + system are constructed by using the neural network method. Ab initio energy points are calculated using the multi-reference configuration interaction method with the Davidson correction and AVQZ basis set. The diabatic energies are obtained from the transformation of ab initio data based on the dipole moment operators. The topographical characteristics of the diabatic PESs are described in detail, and the positions of crossing between the V d 11 and V d 22 are pinpointed. On new diabatic PESs, the time-dependent quantum wave packet method is carried out to study the mechanism of the title reaction. The results of dynamics calculations indicate the reaction has no threshold and the product BeH+ is excited to high vibrational states easily. In addition, the product BeH+ tends to backward scattering at most collision energies.

A new potential energy surface of the OH2+ system and state-to-state quantum dynamics studies of the O+ + H2 reaction.

A new global potential energy surface (PES) of the O+ + H2 system was constructed with the permutation invariant polynomial neural network method, using about 63 000 ab initio points, which were calculated by employing the multi-reference configuration interaction method with aug-cc-pVTZ and aug-cc-pVQZ basis sets. For improving the accuracy of the PES, the basis set was extrapolated to the complete basis set limit by the two-point extrapolation method. The root mean square error of fitting was only 5.28 × 10-3 eV. The spectroscopic constants of the diatomic molecules were calculated and compared with previous theoretical and experimental results, which suggests that the present results agree well with the experiment. On the newly constructed PES, reaction dynamics studies were performed using the time-dependent wave packet method. The calculated integral cross sections (ICSs) were compared with the available theoretical and experimental results, where a good agreement with the experimental data was seen. Significant forward and backward scatterings were observed in the whole collision energy region studied. At the same time, the differential cross sections biased the forward scattering, especially at higher collision energies.

Correction: Global diabatic potential energy surfaces for the BeH2 + system and dynamics studies on the Be+(2P) + H2(X1Σg +) → BeH+(X1Σ+) + H(2S) reaction.

[This corrects the article DOI: 10.1039/C8RA04305A.].

Influence of rovibrational excitation on the non-diabatic state-to-state dynamics for the Li(2p) + H2 → LiH + H reaction.

The non-adiabatic state-to-state dynamics of the Li(2p) + H2 → LiH + H reaction has been studied using the time-dependent wave packet method, based on a set of diabatic potential energy surfaces recently developed by our group. Integral cross sections (ICSs) can be increase more than an order of magnitude by the vibrational excitation of H2, whereas the ICSs are barely affected by the rotational excitation of H2. Moreover, ICSs of the title reaction with vibrationally excited H2 decrease rapidly with increasing collision energy, which is a typical feature of non-threshold reaction. This phenomenon implies that the title reaction can transformed from an endothermic to an exothermic reaction by vibrational excitation of H2. With the increase of the collision energy, the sideways and backward scattered tendencies of LiH for the Li(2p) + H2(v = 0, j = 0, 1) → LiH + H reactions are enhanced slightly, while the backward scattering tendency of LiH for the Li(2p) + H2(v = 1, j = 0) → LiH + H reaction becomes remarkably weakened. For the reaction with vibrationally excited H2 molecule, both direct and indirect reaction mechanism exist simultaneously.

A neural network potential energy surface for the NaH2 system and dynamics studies on the H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+) reaction.

In order to study the dynamics of the reaction H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+), a new potential energy surface (PES) for the ground state of the NaH2 system is constructed based on 35 730 ab initio energy points. Using basis sets of quadruple zeta quality, multireference configuration interaction calculations with Davidson correction were carried out to obtain the ab initio energy points. The neural network method is used to fit the PES, and the root mean square error is very small (0.00639 eV). The bond lengths, dissociation energies, zero-point energies and spectroscopic constants of H2(X1Σg+) and NaH(X1Σ+) obtained on the new NaH2 PES are in good agreement with the experiment data. On the new PES, the reactant coordinate-based time-dependent wave packet method is applied to study the reaction dynamics of H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+), and the reaction probabilities, integral cross-sections (ICSs) and differential cross-sections (DCSs) are obtained. There is no threshold in the reaction due to the absence of an energy barrier on the minimum energy path. When the collision energy increases, the ICSs decrease from a high value at low collision energy. The DCS results show that the angular distribution of the product molecules tends to the forward direction. Compared with the LiH2 system, the NaH2 system has a larger mass and the PES has a larger well at the H-NaH configuration, which leads to a higher ICS value in the H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+) reaction. Because the H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+) reaction releases more energy, the product molecules can be excited to a higher vibrational state.

A new potential energy surface of LiHCl system and dynamic studies for the Li(2S) + HCl(X1Σ+) → LiCl(X1Σ+) + H(2S) reaction.

A new global potential energy surface (PES) is constructed for the ground state of LiHCl system based on high-quality ab initio energy points calculated using multi-reference configuration interaction calculations with the Davidson correction. The AVQZ and WCVQZ basis sets are employed for H and Li atoms, respectively. To compensate the relativistic effects of heavy element, the AWCVQZ-DK basis set is employed for Cl atom. The neural network method is used for fitting the PES, and the root mean square error is small (1.36 × 10-2 eV). The spectroscopic constants of the diatoms obtained from the new PES agree well with experimental data. The geometric characteristics of the transition state and the complex are examined and compared with the previous theoretical values. To study the reaction dynamics of the Li(2S) + HCl(X1Σ+) → LiCl(X1Σ+) + H(2S) reaction, quantum reactive scattering dynamics calculations using collection reactant-coordinate-based wave packet method are conducted based on the new PES. The results of the reaction probabilities indicate that a small barrier exists along the reaction path as observed from the PES. The integral cross section curves reveal that the product molecule LiCl is easily excited. In addition, the reaction is dominated by forward scattering, and similar pattern is observed from Becker's experiment.

Global diabatic potential energy surfaces and quantum dynamical studies for the Li(2p) + H2(X(1)Σ(+)g) → LiH(X(1)Σ(+)) + H reaction.

The global diabatic potential energy surfaces which are correlated with the ground state 1A' and the excited state 2A' of the Li(2p) + H2 reaction are presented in this study. The multi-reference configuration interaction method and large basis sets (aug-cc-pVQZ for H atom and cc-pwCVQZ for Li atom) were employed in the ab initio single-point energy calculations. The diabatic potential energies were generated by the diabatization scheme based on transition dipole moment operators. The neural network method was utilized to fit the matrix elements of the diabatic energy surfaces, and the root mean square errors were extremely small (3.69 meV for , 5.34 meV for and 5.06 meV for ). The topographical features of the diabatic potential energy surfaces were characterized and the surfaces were found to be sufficiently smooth for the dynamical calculation. The crossing seam of the conical intersections between the and surfaces were pinpointed. Based on this new analytical diabatic potential energy surfaces, time-dependent wave packet calculation were conducted to investigate the mechanism of the title reaction. At low collision energies, the product LiH molecule tends to forward scattering, while at high collision energies, the forward and backward scatterings exist simultaneously.

A new potential energy surface for the H2S system and dynamics study on the S((1)D) + H2(X(1)Σg(+)) reaction.

We constructed a new global potential energy surface (PES) for the electronic ground state ((1)A') of H2S based on 21,300 accurate ab initio energy points over a large configuration space. The ab initio energies are obtained from multireference configuration interaction calculations with a Davidson correction using basis sets of quadruple zeta quality. The neural network method is applied to fit the PES, and the root mean square error of fitting is small (1.68 meV). Time-dependent wave packet studies for the S((1)D) + H2(X(1)Σg(+)) → H((2)S) + SH(X(2)Π) reaction on the new PES are conducted to study the reaction dynamics. The calculated integral cross sections decrease with increasing collision energy and remain fairly constant within the high collision energy range. Both forward and backward scatterings can be observed as expected for a barrierless reaction with a deep well on the PES. The calculated integral cross sections and differential cross sections are in good agreement with the experimental results.

A new potential energy surface for the ground electronic state of the LiH2 system, and dynamics studies on the H((2)S) + LiH(X(1)Σ(+)) → Li((2)S) + H2(X(1)Σg(+)) reaction.

A new global potential energy surface (PES) is obtained for the ground electronic state of the LiH2 system based on high-level energies. The energy points are calculated at the multireference configuration interaction level with aug-cc-pVXZ (X = Q, 5) basis sets, and these energies are extrapolated to the complete basis set limit. The neural network method and hierarchical construction scheme are applied in the fitting process and the root mean square error of the fitting result is very small (0.004 eV). The dissociation energies and equilibrium distances for LiH(X(1)Σ(+)) and H2(X(1)Σg(+)) obtained from the new PES are in good agreement with the experimental data. On the new PES, time-dependent wave packet studies for the H((2)S) + LiH(X(1)Σ(+)) → Li((2)S) + H2(X(1)Σg(+)) reaction have been carried out. In this reaction, no threshold is found due to the absence of an energy barrier on the minimum energy path. The calculated integral cross sections are high at low collision energy and will decrease with the increase of the collision energy. The product molecule H2 tends to be forward scattering due to direct reactive collisions, which becomes more evident at higher collision energies.

State-resolved time-dependent wave packet and quasiclassical trajectory studies of the adiabatic reaction S(3P) + HD on the (1(3)A″) state.

Time-dependent wave packet (TDWP) and quasiclassical trajectory (QCT) calculations have been carried out for the reaction S(3P) + HD(X1Σg+) at the lowest 13A″ state with both rotational and vibrational excitations of reactant HD. The calculated integral cross sections from QCT agree fairly well with the TDWP calculations. The reaction probability results from TDWP show that the reaction displays a strong tendency to the SD channel. When the reactant HD is vibrationally excited, both channels are promoted apparently. The vibration of the HD bond tends to reduce the difference of reactivity between the two channels. The detailed state-to-state differential cross sections (DCSs) are calculated. These distributions show some significant characters of the barrier-type reactions. At the same time, the scattering width of product SD has a certain relationship with its rotation excitation. For the vector properties, P(θr), P(r), and P(θr,r) distributions are calculated by QCT, and the increased collision energy weakens the rotational polarization of the SD molecule.

Accurate double many-body expansion potential energy surface by extrapolation to the complete basis set limit and dynamics calculations for ground state of NH2.

An accurate single-sheeted double many-body expansion potential energy surface is reported for the title system. A switching function formalism has been used to warrant the correct behavior at the H2(X1Σg+)+N(2D) and NH (X3Σ-)+H(2S) dissociation channels involving nitrogen in the ground N(4S) and first excited N(2D) states. The topographical features of the novel global potential energy surface are examined in detail, and found to be in good agreement with those calculated directly from the raw ab initio energies, as well as previous calculations available in the literature. The novel surface can be using to treat well the Renner-Teller degeneracy of the 12A″ and 12A' states of NH 2. Such a work can both be recommended for dynamics studies of the N(2D)+H2 reaction and as building blocks for constructing the double many-body expansion potential energy surface of larger nitrogen/hydrogen-containing systems. In turn, a test theoretical study of the reaction N(2D)+H2(X1Σg+)(ν=0,j=0)→NH (X3Σ-)+H(2S) has been carried out with the method of quantum wave packet on the new potential energy surface. Reaction probabilities, integral cross sections, and differential cross sections have been calculated. Threshold exists because of the energy barrier (68.5 meV) along the minimum energy path. On the curve of reaction probability for total angular momentum J = 0, there are two sharp peaks just above threshold. The value of integral cross section increases quickly from zero to maximum with the increase of collision energy, and then stays stable with small oscillations. The differential cross section result shows that the reaction is a typical forward and backward scatter in agreement with experimental measurement result.