Electronic Structures and Mobilities of 2,2\u27-diphenyl-5,5\u27-bithiazole Derivatives

Density functional theory calculations were performed on 2,2\u27-diphenyl-5,5\u27-bithiazole (DPBT) and its derivatives. The dimer structures of the title compounds were optimized by a density functional theory method with dispersion energy being considered at the wB97XD/LanL2DZ level. Reorganization energies between the switch of neutral molecules and anion radicals, and the electron-transfer coupling matrix were obtained. By using the Marcus theory and the Einstein relation, the electron hopping rates and mobilities were predicted. The electron mobility of difluorinated 2,2\u27-diphenyl-5,5\u27-bithiazole (2A) was predicted to be 1.179 cm2 V–1 s–1, which is the largest value among the title compounds. The large electron mobility of 2A is mainly owing to its large transfer coupling matrix since its LUMO consists of some overlaps between two submolecular orbitals. Our results indicate that a moderate fluorination of DPBT, instead of as many as possible substituents of fluorines, considerably facilitates the electronic mobility of n-type organic semiconductors. This work is licensed under a Creative Commons Attribution 4.0 International License

Unconventional Origin and Hybrid System for Construction of Pyrrolopyrrole Moiety in Kosinostatin Biosynthesis

SummaryKosinostatin (KST), an antitumor antibiotic, features a pyrrolopyrrole moiety spirally jointed to a five-membered ring of an anthraquinone framework glycosylated with a γ-branched octose. By a combination of in silico analysis, genetic characterization, biochemical assay, and precursor feeding experiments, a biosynthetic pathway for KST was proposed, which revealed (1) the pyrrolopyrrole moiety originates from nicotinic acid and ribose, (2) the bicyclic amidine is constructed by a process similar to the tryptophan biosynthetic pathway, and (3) a discrete adenylation enzyme and a peptidyl carrier protein (PCP) are responsible for producing a PCP-tethered building block parallel to type II polyketide synthase (PKS) rather than for the PKS priming step by providing the starter unit. These findings provide an opportunity to further explore the inexplicable enzymatic logic that governs the formation of pyrrolopyrrole moiety and the spirocyclic skeleton

Screening Quality Evaluation Factors of Freeze-Dried Peach ( Prunus Persica

The quality evaluation of processed products is complex. To simplify the quality evaluation process and improve the efficiency, fourteen evaluation factors of freeze-dried powders of seventeen cultivars of peach at different ripening times were analyzed. The most important evaluation indicators and criteria were obtained by analysis of variance (ANOVA), correlation analysis (CA), principal component analysis (PCA), system cluster analysis (SCA), and analytic hierarchy process (AHP). Results showed that the peach powders had the significant differences in quality (P<0.05), and some processing factors were related with some physicochemical and nutritional factors. Five principle components were extracted by PCA and the cumulative contribution achieved was 84.46%. Through the score plot of the first two principal components, a clear differentiation among ripening times was found and three distinct groups were separated according to ripening time. Five characteristic factors were obtained as titratable acid, browning index, hemicellulose, hygroscopicity, and vitamin C by SCA. Their weights of 0.1249, 0.3007, 0.0514, 0.4916, and 0.0315 were obtained by AHP, respectively. The peach cultivars were divided into four evaluation grades by the comprehensive quality score

Initial Decomposition Reactions of Bicyclo-HMX [BCHMX or cis-1,3,4,6-Tetranitrooctahydroimidazo-[4,5-d]imidazole] from Quantum Molecular Dynamics Simulations

We investigated the initial chemical reactions of BCHMX [cis-1,3,4,6-tetranitrooctahydroimidazo-[4,5-d]imidazole] with the following procedure. First we used density functional theory molecular dynamics simulations (DFT-MD) on the periodic crystal to discover the initial reaction steps. This allowed us to determine the most important reactions through DFT-MD simulations at high temperatures. Then we started with the midpoint of the reaction (unimolecular or bimolecular) from the DFT-MD and carried out higher quality finite cluster DFT calculations to locate the true transition state of the reaction, followed by calculations along the reaction path to determine the initial and final states. We find that for the noncompressed BCHMX the nitro-aci isomerization reaction occurs earlier than the NO_2-releasing reaction, while for compressed BCHMX intermolecular hydrogen-transfer and bimolecular NO_2-releasing reactions occur earlier than the nitrous acid (HONO)-releasing reaction. At high pressures, the initial reaction involves intermolecular hydrogen transfer rather than intramolecular hydrogen transfer, and the intermolecular hydrogen transfer decreases the reaction barrier for release of NO_2 by ∼7 kcal/mol. Thus, the HONO-releasing reaction takes place more easily in compressed BCHMX. We find that this reaction barrier is 10 kcal/mol lower than the unimolecular NO_2 release and ∼3 kcal/mol lower than the bimolecular NO_2 release. This rationalizes the origin of the higher sensitivity of BCHMX compared to RDX (1,3,5-trinitrohexahydro-1,3,5-triazine) and HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine). We suggest changes in BCHMX that might help decrease the sensitivity by avoiding the intermolecular hydrogen-transfer and HONO-releasing reaction

Reaction mechanism from quantum molecular dynamics for the initial thermal decomposition of 2,4,6-triamino-1,3,5-triazine-1,3,5-trioxide (MTO) and 2,4,6-trinitro-1,3,5-triazine-1,3,5-trioxide (MTO3N), promising green energetic materials

Klapötke and co-workers recently designed two new materials, 2,4,6-triamino-1,3,5-triazine-1,3,5-trioxide (MTO) and 2,4,6-trinitro-1,3,5-triazine-1,3,5-trioxide (MTO3N), envisioned as candidates for green high-energy materials. However, all attempts at synthesis have failed. In order to validate the expected properties for these systems and to determine why these materials are too unstable to synthesize, we used the PBE flavor of Density Functional Theory (DFT) to predict the crystal structures for MTO and MTO3N and then we carried out DFT molecular dynamics simulations (DFT-MD) to determine the initial reaction mechanisms for decomposition. Klapötke estimated that MTO would have a density of ρ = 1.859 g cm^(−3) with an estimated detonation velocity (D_v) of 8.979 km s^(−1), making it comparable to RDX (ρ = 1.82 g cm^(−3), D_v = 8.75 km s^(−1)) and β-HMX (ρ = 1.91 g cm^(−3), D_v = 9.10 km s^(−1)). His estimated impact sensitivity >30 J, make it much better than HMX (7 J) and RDX (7.5 J). Our predicted crystal structure for MTO (P2_(1) space group) leads to ρ = 1.859 g cm^(−3), in good agreement with expectations. Our DFT-MD studies find that the first step in the decomposition of MTO is intermolecular hydrogen-transfer reaction (barrier 3.0 kcal mol^(−1)) which is followed quickly by H_2O and NO release with reaction barriers of 46.5 and 35.5 kcal mol^(−1). In contrast for MTO3N (P2_(1)/c predicted space group), we find that the first steps are a bimolecular decomposition to release NO_2 (ΔH = 44.1 kcal mol^(−1), ΔG = 54.7 kcal mol^(−1)) simultaneous with unimolecular NO_2 cleavage (ΔH = 59.9 and ΔG = 58.2 kcal mol^(−1)) a unique initial reaction among EMs. These results suggest that MTO3N would be significantly more thermally stabile (barrier > 6.0 kcal mol^(−1) higher) than RDX and HMX, making it an excellent candidate to be insensitive new green energetic materials. However we find that MTO leads to very favorable hydrogen transfer reactions that may complicate synthesis and crystallization, making MTO3N the more promising system

Initial decomposition reaction of di-tetrazine-tetroxide (DTTO) from quantum molecular dynamics: implications for a promising energetic material

Di-tetrazine-tetroxide (DTTO) was predicted in 2001 to have a density (up to 2.3 g cm^(−3)) and heat of detonation (up to 421.0 kcal mol^(−1)) better than other explosives, making it the “holy grail” of energetic materials (EMs), but all attempts at synthesis have failed. We report Density Functional Theory (DFT) molecular dynamics simulations (DFT-MD) on DTTO crystal for the two most stable monomers. We predict that the most stable isomer (c1) has a density of ρ = 1.96 g cm^(−3) with an estimated detonation velocity (D_v) of 9.70 km s^(−1) and a detonation pressure (D_p) of 43.0 GPa, making it comparable to RDX (ρ = 1.82 g cm^(−3), D_v = 8.75 km s^(−1), D_p = 35.0 GPa), HMX (ρ = 1.91 g cm^(−3), D_v = 9.10 km s^(−1), D_p = 39.3 GPa) and CL-20 (ρ = 2.04 g cm^(−3), D_v = 9.38 km s^(−1), D_p = 44.1 GPa). The DFT-MD studies find that the initial reaction at lower pressure is unimolecular decomposition to form two N_2O molecules (barrier 45.9 kcal mol^(−1)), while at higher pressure it is intermolecular oxygen-transfer with a barrier of 40.1 kcal mol^(−1). For the c2 isomer (less stable by 1.2 kcal mol^(−1)) the initial reaction involves two DTTO molecules reacting to form a dimer which then releases N_2 as a direct product (barrier 48.1 kcal mol^(−1)), a unique initial reaction among EMs. These results suggest that DTTO may have a higher thermal stability (barrier >7.0 kcal mol^(−1) higher) than RDX, HMX, and CL-20

AI protein structure prediction-based modeling and mutagenesis of a protostome receptor and peptide ligands reveal key residues for their interaction

The protostome leucokinin (LK) signaling system, including LK peptides and their G protein-coupled receptors, has been characterized in several species. Despite the progress, molecular mechanisms governing LK peptide–receptor interactions remain to be elucidated. Previously, we identified a precursor protein for Aplysia leucokinin-like peptides (ALKs) that contains the greatest number of amidated peptides among LK precursors in all species identified so far. Here, we identified the first ALK receptor from Aplysia, ALKR. We used cell-based IP1 activation assays to demonstrate that two ALK peptides with the most copies, ALK1 and ALK2, activated ALKR with high potencies. Other endogenous ALK-derived peptides bearing the FXXWX-amide motif also activated ALKR to various degrees. Our examination of cross-species activity of ALKs with the Anopheles LK receptor was consistent with a critical role for the FXXWX-amide motif in receptor activity. Furthermore, we showed, through alanine substitution of ALK1, the highly conserved phenylalanine (F), tryptophan (W), and C-terminal amidation were each essential for receptor activation. Finally, we used an artificial intelligence– based protein structure prediction server (Robetta) and Autodock Vina to predict the ligand-bound conformation of ALKR. Our model predicted several interactions (i.e., hydrophobic interactions, hydrogen bonds, and amide-pi stacking) between ALK peptides and ALKR, and several of our substitution and mutagenesis experiments were consistent with the predicted model. In conclusion, our results provide important information defining possible interactions between ALK peptides and their receptors. The workflow utilized here may be useful for studying other ligand–receptor interactions for a neuropeptide signaling system, particularly in protostomes

Characterization of an Aplysia vasotocin signaling system and actions of posttranslational modifications and individual residues of the ligand on receptor activity

The vasopressin/oxytocin signaling system is present in both protostomes and deuterostomes and plays various physiological roles. Although there were reports for both vasopressin-like peptides and receptors in mollusc Lymnaea and Octopus, no precursor or receptors have been described in mollusc Aplysia. Here, through bioinformatics, molecular and cellular biology, we identified both the precursor and two receptors for Aplysia vasopressin-like peptide, which we named Aplysia vasotocin (apVT). The precursor provides evidence for the exact sequence of apVT, which is identical to conopressin G from cone snail venom, and contains 9 amino acids, with two cysteines at position 1 and 6, similar to nearly all vasopressin-like peptides. Through inositol monophosphate (IP1) accumulation assay, we demonstrated that two of the three putative receptors we cloned from Aplysia cDNA are true receptors for apVT. We named the two receptors as apVTR1 and apVTR2. We then determined the roles of post-translational modifications (PTMs) of apVT, i.e., the disulfide bond between two cysteines and the C-terminal amidation on receptor activity. Both the disulfide bond and amidation were critical for the activation of the two receptors. Cross-activity with conopressin S, annetocin from an annelid, and vertebrate oxytocin showed that although all three ligands can activate both receptors, the potency of these peptides differed depending on their residue variations from apVT. We, therefore, tested the roles of each residue through alanine substitution and found that each substitution could reduce the potency of the peptide analog, and substitution of the residues within the disulfide bond tended to have a larger impact on receptor activity than the substitution of those outside the bond. Moreover, the two receptors had different sensitivities to the PTMs and single residue substitutions. Thus, we have characterized the Aplysia vasotocin signaling system and showed how the PTMs and individual residues in the ligand contributed to receptor activity