Finite temperature string by K-means clustering sampling with order parameters as collective variables for molecular crystals: application to polymorphic transformation between ß-CL-20 and ε-CL-20.

Polymorphic transformation of molecular crystals is a fundamental phase transition process, and it is important practically in the chemical, material, biopharmaceutical, and energy storage industries. However, understanding of the transformation mechanism at the molecular level is poor due to the extreme simulating challenges in enhanced sampling and formulating order parameters (OPs) as the collective variables that can distinguish polymorphs with quite similar and complicated structures so as to describe the reaction coordinate. In this work, two kinds of OPs for CL-20 were constructed by the bond distances, bond orientations and relative orientations. A K-means clustering algorithm based on the Euclidean distance and sample weight was used to smooth the initial finite temperature string (FTS), and the minimum free energy path connecting ß-CL-20 and ε-CL-20 was sketched by the string method in collective variables, and the free energy profile along the path and the nucleation kinetics were obtained by Markovian milestoning with Voronoi tessellations. In comparison with the average-based sampling, the K-means clustering algorithm provided an improved convergence rate of FTS. The simulation of transformation was independent of OP types but was affected greatly by finite-size effects. A surface-mediated local nucleation mechanism was confirmed and the configuration located at the shoulder of potential of mean force, rather than overall maximum, was confirmed to be the critical nucleus formed by the cooperative effect of the intermolecular interactions. This work provides an effective way to explore the polymorphic transformation of caged molecular crystals at the molecular level.

Strong External Electric Fields Reduce Explosive Sensitivity: A Theoretical Investigation into the Reaction Selectivity in NH2NO2∙∙∙NH3.

Controlling the selectivity of a detonation initiation reaction of explosive is essential to reduce sensitivity, and it seems impossible to reduce it by strengthening the external electric field. To verify this, the effects of external electric fields on the initiation reactions in NH2NO2∙∙∙NH3, a model system of the nitroamine explosive with alkaline additive, were investigated at the MP2/6-311++G(2d,p) and CCSD(T)/6-311++G(2d,p) levels. The concerted effect in the intermolecular hydrogen exchange is characterized by an index of the imaginary vibrations. Due to the weakened concerted effects by the electric field along the -x-direction opposite to the "reaction axis", the dominant reaction changes from the intermolecular hydrogen exchange to 1,3-intramolecular hydrogen transference with the increase in the field strengths. Furthermore, the stronger the field strengths, the higher the barrier heights become, indicating the lower sensitivities. Therefore, by increasing the field strength and adjusting the orientation between the field and "reaction axis", not only can the reaction selectivity be controlled, but the sensitivity can also be reduced, in particular under a super-strong field. Thus, a traditional concept, in which the explosive is dangerous under the super-strong external electric field, is theoretically broken. Compared to the neutral medium, a low sensitivity of the explosive with alkaline can be achieved under the stronger field. Employing atoms in molecules, reduced density gradient, and surface electrostatic potentials, the origin of the reaction selectivity and sensitivity change is revealed. This work provides a new idea for the technical improvement regarding adding the external electric field into the explosive system.

Fault diagnosis method of bearing utilizing GLCM and MBASA-based KELM.

In this study, fault diagnosis method of bearing utilizing gray level co-occurrence matrix (GLCM) and multi-beetles antennae search algorithm (MBASA)-based kernel extreme learning machine (KELM) is presented. In the proposed method, feature extraction of time-frequency image based on GLCM is proposed to extract the features of the bearing vibration signal, and multi-beetles antennae search algorithm-based KELM (MBASA-KELM) is presented to recognize the states of bearing. KELM employs the kernel-based framework, which has better generalization than traditional extreme learning machine, and it is necessary to look for an excellent optimization algorithm to select appropriate regularization parameter and kernel parameter of the KELM model because these parameters of the KELM model can affect its performance. As traditional beetle antennae search algorithm only employs one beetle, which is difficult to find the optimal parameters when the ranges of the parameters to be optimized are wide, multi-beetles antennae search algorithm (MBASA) employing multi-beetles is presented to select the regularization parameter and kernel parameter of KELM. The experimental results demonstrate that MBASA-KELM has stronger fault diagnosis ability for bearing than LSSVM, and KNN.

Facile construction of shape-regulated ß-cyclodextrin-based supramolecular self-assemblies for drug delivery.

Although supramolecular prodrug self-assemblies have been proven as efficient nanocarriers for cancer therapy, tedious synthesis procedures have made their practical applications more difficult. In this paper, ß-cyclodextrin-based supramolecular self-assemblies (SSAs) were directly constructed by utilizing ß-cyclodextrin trimer (ß-CD3) as the host unit and unmodified curcumin as the guest unit. Due to the adjustment of host-guest inclusion and hydrophilic-hydrophobic interactions occurring in the SSAs, their morphology could be readily tuned by changing the ratio of the two components. Different self-assembly morphologies, such as spherical complex micelles, spindle-like complex micelles and multi-compartment vesicles, were obtained. Furthermore, basic cell experiments were performed to study the corresponding effects of the SSA shape on their biological properties. Compared to the other micelles, the spindle-like complex micelles exhibited enhanced cellular toxicity, uptake behaviors and apoptosis rates, and the spherical complex micelles exhibited poor performance. The performance of the multi-compartment vesicles was similar to that of the spindle-like complex micelles. The facile construction of these shape-regulated SSAs and their different cellular biological properties might be valuable in the controlled drug release field.

Roads to pentazolate anion: a theoretical insight.

The formation mechanism of pentazolate anion (PZA) is not yet clear. In order to present the possible formation pathways of PZA, the potential energy surfaces of phenylpentazole (PPZ), phenylpentazole radical (PPZ-R), phenylpentazole radical anion (PPZ-RA), PPZ and m-chloroperbenzoic acid (m-CPBA), p-pentazolylphenolate anion (p-PZPolA) and m-CPBA, and p-pentazolylphenol (p-PZPol) and m-CPBA were calculated by the computational electronic structure methods including the hybrid density functional, the double hybrid density functional and the coupled-cluster theories. At the thermodynamic point of view, the cleavages of C-N bonds of PPZ and PPZ-R need to absorb large amounts of heat. Thus, they are not feasible entrance for PZA formation at ambient condition. But excitation of PPZ and deprotonation of PPZ-RA probably happen before cleavage of C-N bond of PPZ at high-energy condition. As to the radical anion mechanism, the high accuracy calculations surveyed that the barrier of PZA formation is probably lower than that of dinitrogen evolution, but the small ionization potential of PPZ-RA gives rise to the unstable ionic pair of sodium PPZ at high temperature. In respect of oxidation mechanism, except for PPZ, the reactions of p-PZPolA and p-PZPol with m-CPBA can form PZA and quinone. The PZA formations have the barriers of about 20 kcal mol-1 which compete with the dinitrogen evolutions. The stabilities of PZA in both solid and gas phases were also studied herein. The proton prefers to transfer to pentazolyl group in the (N5)6(H3O)3(NH4)4Cl system which leads to the dissociation of pentazole ring. The ground states of M(N5)2(H2O)4 (M = Co, Fe and Mn) are high-spin states. The pentazolyl groups confined by the crystal waters in the coordinate compounds can improve the kinetic stability. As to the reactivity of PZA, it can be persistently oxidized by m-CPBA to oxo-PZA and 1,3-oxo-PZA with the barriers of about 20 kcal mol-1.

Study on the computer-aided design of high energetic compounds based on the 1,2,3,4-tetrazine-1,3-dioxide frame.

In order to discover more potential high energy compounds, five computer-aided design methods were founded, and 20 high energetic compounds based on the 1,2,3,4-tetrazine-1,3-dioxide frame were designed. The first step of computer-aided design methods was to design new frame M. Three combination rules were invented, they were simple double-points rule, complicated double-points rule, and complicated multi-points rule. The second step of computer-aided design methods was to design 1,2,3,4-tetrazine 1,3-dioxides derivants by connecting M to 1,2,3,4-tetrazine-1,3-dioxides. Two combination rules were invented, they were simple single-points rule and double-points rule. All the structures are ring-fused or caged compounds including 1,2,3,4-tetrazine-1,3-dioxide. In these compounds, almost half of them have positive or zero oxygen balances, and the nitrogen contents of 17 compounds are over 40%. The densities and detonation velocities of all compounds are over 1.98 g cm-3 and 9500 m s-1 respectively. -N = N- group and -NO2 group have a major contribution to enthalpy of formation, detonation heat, and power index. -O- group and -ONO2 group have the main contribution to density, detonation velocity, and detonation pressure.

Theoretical study of the effect of N-oxides on the performances of energetic compounds.

In order to study the effects of N-oxide on structure and performance, six categories of energetic compounds were systemically investigated. The results indicated that the C-C bonds in the rings were shortened, and the C-N bonds close to the N → O bond were elongated when N atoms was oxidized to form N → O bonds. N → O bonds can increase the densities of most categories of compounds, and the increment will increase with the number of N → O bonds. As to their detonation performances, almost all categories of compounds had an increased trend, except for some NO2-, NHNO2- and ONO2-substituted compounds. The contribution of 1,2,3,4-tetrazine and 1,2,4,5-tetrazine to performances was better than that of pyrazine and [1,2,5] oxadiazolo [3,4-b] pyrazine on the whole, and the groups, especially energetic groups, made a huge contribution to performance. When R was a NH2 or ONO2 group, all compounds had lower impact sensitivities, and thus represent candidates for novel energetic compounds. However, other than the sixth category of compounds, all compounds had higher impact sensitivities when R was a NO2 or NHNO2 group, and have little significance in application.

Design and theoretical study of 15 novel high energy density compounds.

In order to seek the potential high energy density compounds (HEDCs) with excellent performance and satisfactory safety, some combination rules are presented and 15 HEDCs are designed and sifted, and followed by the properties predicting. From the results, HEDC-3, HEDC-4, HEDC-9, HEDC-10, HEDC-11, HEDC-12, HEDC-13, and HEDC-14 have good comprehensive properties. They are furoxan, fused ring or cage-type compounds, whose frame is composed of some single ring by single (double or multi) point addition. Their densities are over 1.95 g cm(-3), and detonation velocities are over 9500 m s(-1). Their BDEs are over 85 kJ mol(-1), and the values of available free space (∆V) are lower than the ∆V of ß-CL20 (∆V = 86). In view of the synthesis feasibility, the synthesis routes of HEDC-4, HEDC-9, HEDC-10, HEDC-12, HEDC-13, and HEDC-14 have been designed.

Theoretical study on the structure and stability of [1,2,5] oxadiazolo [3,4-e] [1,2,3,4]-tetrazine-4,6-Di-N-dioxide (FTDO).

Although many 1,2,3,4-tetrazine-1,3-dioxide derivates have been synthesized, [1,2,5] oxadiazolo [3,4-e] [1,2,3,4]-tetrazine-4,6-di-N-dioxide (FTDO) is the only one with high enthalpy of formation and high detonation velocity. Whereas, its stability has not been studied. In the present work, the structure of FTDO was investigated using density functional theory (DFT) method, and its stability was calculated by potential energy surface scanning and structure interconvert thermodynamics under different temperatures. The spontaneous isomerization of FTDO and its effect on the stability of FTDO were investigated. The dissociation of FTDO to N2, N2O and furoxan fragments was studied, and the possibility of synthetic route from FTDO to TTTO was discussed.

[Effect of ethyl acetate extract of sappan wood on expression of myocardial GrB mRNA in rat model of allogeneic ectopic cardiac transplantation].

OBJECTIVE: To explore the action mechanism of the immune active components of sappon wood (SWE) for antagonizing reject reaction by observing the influence of its ethyl acetate extract on mRNA expression of myocardial GrB in rat model of allogenic ectopic cardiac transplantation. METHODS: Animal model of abdominal cardiac ectopic transplantation was established taking Wistar rat as the donor and SD rat as the receptor. The successfully modeled rats were randomly divided into the model group, the SWE group and the CsA group. GrB mRNA expression was detected by RT-PCR method and myocardial pathomorphologic picture was observed in routine. RESULTS: The pathologic changes in the SWE group (23 scores) and the CsA group (14 scores) were milder than in the model group (31 scores), the former two could markedly alleviate the myocardial pathologic injury (P<0.05, P<0.01). The GrB mRNA expression in the model group was 1.3000 +/- 0.1207, the SWE group 0. 7070 +/- 0.1215, and the CsA group 0.6700 +/- 0.0997, respectively; compared with the model group, the latter two could obviously down-regulate the expression of GrB mRNA (P<0.01) and no significant difference was found between the latter two groups (P>0.05). CONCLUSION: SWE could alleviate the pathologic change, down-regulate the mRNA expression of myocardial GrB in allogenic ectopic transplanted myocardium of rats, it is possibly one of the factors for its antagonizing effect against reject reaction.