Structural Assignment Research Articles

Synthesis, Characterizations, and Quantum Chemical Investigations on Imidazo[1,2-a]pyrimidine-Schiff Base Derivative: (E)-2-Phenyl-N-(thiophen-2-ylmethylene)imidazo[1,2-a]pyrimidin-3-amine.

In this study, (E)-2-phenyl-N-(thiophen-2-ylmethylene)imidazo[1,2-a]pyrimidin-3-amine (3) is synthesized, and detailed spectral characterizations using 1H NMR, 13C NMR, mass, and Fourier transform infrared (FT-IR) spectroscopy were performed. The optimized geometry was computed using the density functional theory method at the B3LYP/6-311++G(d,p) basis set. The theoretical FT-IR and NMR (1H and 13C) analysis are agreed to validate the structural assignment made for (3). Frontier molecular orbitals, molecular electrostatic potential, Mulliken atomic charge, electron localization function, localized orbital locator, natural bond orbital, nonlinear optical, Fukui functions, and quantum theory of atoms in molecules analyses are undertaken and meticulously interpreted, providing profound insights into the molecular nature and behaviors. In addition, ADMET and drug-likeness studies were carried out and investigated. Furthermore, molecular docking and molecular dynamics simulations have been studied, indicating that this is an ideal molecule to develop as a potential vascular endothelial growth factor receptor-2 inhibitor.

106-fold faster C-H bond hydroxylation by a CoIII,IV2(µ-O)2 complex [via a CoIII2(µ-O)(µ-OH) intermediate] versus its FeIIIFeIV analog.

The hydroxylation of C-H bonds can be carried out by the high-valent CoIII,IV2(µ-O)2 complex 2a supported by the tetradentate tris(2-pyridylmethyl)amine ligand via a CoIII2(µ-O)(µ-OH) intermediate (3a). Complex 3a can be independently generated either by H-atom transfer (HAT) in the reaction of 2a with phenols as the H-atom donor or protonation of its conjugate base, the CoIII2(µ-O)2 complex 1a. Resonance Raman spectra of these three complexes reveal oxygen-isotope-sensitive vibrations at 560 to 590 cm-1 associated with the symmetric Co-O-Co stretching mode of the Co2O2 diamond core. Together with a Co•••Co distance of 2.78(2) Å previously identified for 1a and 2a by Extended X-ray Absorption Fine Structure (EXAFS) analysis, these results provide solid evidence for their "diamond core" structural assignments. The independent generation of 3a allows us to investigate HAT reactions of 2a with phenols in detail, measure the redox potential and pKa of the system, and calculate the O-H bond strength (DO-H) of 3a to shed light on the C-H bond activation reactivity of 2a. Complex 3a is found to be able to transfer its hydroxyl ligand onto the trityl radical to form the hydroxylated product, representing a direct experimental observation of such a reaction by a dinuclear cobalt complex. Surprisingly, reactivity comparisons reveal 2a to be 106-fold more reactive in oxidizing hydrocarbon C-H bonds than corresponding FeIII,IV2(µ-O)2 and MnIII,IV2(µ-O)2 analogs, an unexpected outcome that raises the prospects for using CoIII,IV2(µ-O)2 species to oxidize alkane C-H bonds.

Spectroscopic, quantum computational, topological, Fukui functions and molecular docking analysis on a potential anti-cancer molecule Nicotinamide by DFT method

Nicotinamide has been identified as an anti-oxidant, anti-inflammatory and anti-tumorigenic activity in the medical field. To evaluate the cytotoxic effects of nicotinamide against cancer cells; a detailed spectroscopic investigation was made and examined through FT-IR, FT-Raman and UV–Vis techniques. For quantum computational calculation, the DFT method was performed in order to identify the structural and vibrational assignments of the molecule on the basis of the potential energy distribution. The Time-dependent DFT method was applied to compute electronic excitation and predict UV–Vis spectra. The molecular electrostatic potential, frontier molecular orbitals, natural bond orbital, electronic localization function and localized orbital locator were analyzed to study the topological, chemical reactivity and bioactivity nature of the molecule by suitable computational techniques. The scatter plot of the reduced density gradients was constructed to predict the weak interactions. In addition to these analyses, the local reactivity descriptors like the local softness and Fukui functions were obtained. Furthermore, the molecular docking studies of the molecule were carried out to analyze the biological activity against cancer cells with the target proteins under the class of Poly (adenosine diphosphate-ribose) polymerase enzyme inhibitors and the respective docking parameters were calculated. As per the investigation, the anti-cancer activity had revealed based on molecular docking analysis and it had been identified that the nicotinamide molecule could act as a good inhibitor against cancer.

1,6-Dioxo-2-azaspiro[3.4]oct-2-enes and Related Spirocycles: Heterocycles from [3 + 2] Nitrile Oxide Cycloadditions with 2-Methyleneoxetanes, -Thietanes, and -Azetidines.

Isoxazolines and 4-membered heterocycles are significant structural motifs in numerous synthetic intermediates and natural products. [3 + 2] Cycloadditions between enol ethers and nitrile oxides have been well studied; however, nitrile oxide cycloadditions with 4-membered heterocycles to give spiroisoxazolines are unreported. Here, we showcase the regio- and diastereoselective [3 + 2] nitrile oxide cycloadditions of 2-methyleneoxetanes, -azetidines, and -thietanes to give an array of 1,6-dioxo-2-azaspiro[3.4]oct-2-enes and related spirocycles. 2D NMR experiments suggested that most of the observed diastereoselectivities were dictated by steric interactions; however, dipolarophiles with H bonding donors reversed the stereochemical outcome. X-ray crystallography confirmed the structural assignments.

Probing Radical Addition to 1-Phosphabutadienes by Employing Muonium as a "Light Isotope" of Hydrogen.

Understanding free radical addition to multiple bonds is important to elucidating the mechanistic details of addition polymerization reactions, albeit the fleeting radical intermediates are very difficult to detect by conventional methodologies. Muon spin spectroscopy (μSR) is a highly sensitive method that can detect radical species at 106 spins (cf. EPR: 1012 spins, NMR: 1018 spins). Herein, we employ μSR to detect the radical-addition products from three 1-phosphabutadiene monomers, P-analogues of isoprene. We show that muonium (Mu), a "light" H-atom surrogate, adds predominantly at the C4 position of the P1 =C2 -C3 =C4 moiety to give unprecedented 1-phosphaallyl radicals as the major products. Our structural assignments are supported by assignment of muon, phosphorus and proton hyperfine coupling constants using DFT-calculations. A minor radical product is also detected that is tentatively assigned to an PC3 -heterocyclic free radical. On the basis of DFT-predictions, we speculate that its formation may involve initial addition of Mu+ at the C3 position followed by electron capture. These studies provide rare insights into the prospective radical (or cationic) polymerization of 1-phosphabutadienes, which have previously been polymerized using anionic initiation.

Compositional Modeling of VGO Fractions via Analytical Characterization, Structural Assignment, Property Modeling, and Molecular Component Parsing

Compositional Modeling of VGO Fractions via Analytical Characterization, Structural Assignment, Property Modeling, and Molecular Component Parsing

Nitrene C-H Bond Insertion Approach to Carbazolones and Indolones, and a Reactivity Departure for 7-Membered Analogues.

A modular platform for facile access to 1,2,3,9-tetrahydro-4H-carbazol-4-ones (H4 -carbazolones) and 3,4-dihydrocyclopenta[b]indol-1(2H)-ones (H2 -indolones) is described. The requisite 6- and 5-membered 2-arylcycloalkane-1,3-dione precursors were readily obtained through a Cu-catalyzed arylation of 1,3-cyclohexanediones or by a ring expansion of aryl succinoin derivatives. Enolization of one carbonyl group in the diones, conversion to a leaving group, and subsequent azidation gave 2-aryl-3-azidocycloalk-2-en-1-ones. This two-step, one-pot azidation is highly regioselective with unsymmetrically substituted 2-arylcyclohexane-1,3-diones. The regioselectivity, which is important for access to single isomers of 3,3-disubstituted carbazolones, was analyzed mechanistically and computationally. Finally, a Rh-catalyzed nitrene/nitrenoid insertion into the ortho C-H bond of the aryl moiety gave the H4 -carbazolones and H2 -indolones. One carbazolone was elaborated to an intermediate reported in the total synthesis of N-decarbomethoxychanofruticosinate, (-)-aspidospermidine, (+)-kopsihainanine A. With 2-phenylcycloheptane-1,3-dione, prepared from cyclohexanone and benzaldehyde, the azidation reaction was readily accomplished. However, the Rh-catalyzed reaction unexpectedly led to a labile but characterizable azirine rather than the indole derivative. Computations were performed to understand the differences in reactivities of the 5- and 6-membered 2-aryl-3-azidocycloalk-2-en-1-ones in comparison to the 7-membered analogue, and to support the structural assignment of the azirine.

Total Synthesis of Nicrophorusamide A and Structural Disproof of the Proposed Noursamycin A.

Total synthesis of the proposed noursamycin A has been accomplished, which disproves the original structural assignments. The synthetic strategy described herein has also been employed in the first total synthesis of nicrophorusamide A, a cyclopeptide that is structurally related to noursamycin A.

Highly oxidized flavones in Artemisia species – structure revisions and improved UHPLC-MSn analysis

In course of our studies of the aerial parts of Artemisia abrotanum the major methoxyflavonol could be isolated. However, by NMR structural analysis it became obvious that the substitution pattern in ring B differs from reports for casticin (2). The position of methoxyl and hydroxyl groups are interchanged, i.e., the major flavone is actually chrysosplenetin (1). Three structures in A. abrotanum and A. frigida had to be revised. Use of pyridine-d5 instead of DMSO‑d6 made the resolution of the B-ring 1H and 13C NMR signals possible and enabled correct structural assignment by 2D NMR experiments.Results from NMR structure elucidation for A. abrotanum were confirmed by LC-PDA-ESI-MSn analysis when a PFP (pentafluorophenyl) stationary phase with an optimized gradient elution was applied for separation of 1 and 2 instead of a corresponding C-18 phase. Electrospray mass spectrometry (positive and negative mode) with subsequent fragmentation (ESI-MSn) revealed distinctive mass spectral features of both compounds, especially at MS4 level. Several Artemisia extracts including A. annua were analysed on the PFP phase for the presence of 1 and 2.

Integrated optimisation model for airline bank structure and fleet assignment problem

Integrated optimisation model for airline bank structure and fleet assignment problem

Colossal C130 Fullertubes: Soluble [5,5] C130-D5h(1) Pristine Molecules with 70 Nanotube Carbons and Two 30-Atom Hemifullerene End-caps.

We report the seminal experimental isolation and DFT characterization of pristine [5,5] C130-D5h(1) fullertubes. This achievement represents the largest soluble carbon molecule obtained in its pristine form. The [5,5] C130 species is the highest aspect ratio fullertube purified to date and now surpasses the recent gigantic [5,5] C120-D5d(1). In contrast to C90, C100, and C120 fullertubes, the longer C130-D5h has more nanotubular carbons (70) than end-cap fullerenyl atoms (60). Starting from 39,393 possible C130 isolated pentagon rule (IPR) structures and after analyzing polarizability, retention time, and UV-vis spectra, these three layers of data remarkably predict a single candidate isomer and fullertube, [5,5] C130-D5h(1). This structural assignment is augmented by atomic resolution STEM data showing distinctive and tubular "pill-like" structures with diameters and aspect ratios consistent with [5,5] C130-D5h(1) fullertubes. The high selectivity of the aminopropanol reaction with spheroidal fullerenes permits facile separation and removal of fullertubes from soot extracts. Experimental analyses (HPLC retention time, UV-vis, and STEM) were synergistically used (with polarizability and DFT property calculations) to down select and confirm the C130 fullertube structure. Achieving the isolation of a new [5,5] C130-D5h fullertube opens the door to application development and fundamental studies of electron confinement, fluorescence, and metallic character for a fullertube series of molecules with systematic tubular elongation. This [5,5] fullertube family also invites comparative studies with single-walled carbon nanotubes (SWCNTs), nanohorns (SWCNHs), and fullerenes.

Symmetrical and Mixed Tris(acyl)phosphines: Synthesis, Oxidation and Photochemistry.

Herein, we present a convenient synthesis for symmetrical and mixed substituted tris(acyl)phosphines (TAPs) starting from red phosphorus. All TAPs exhibit a phosphaalkene-acylphosphine equilibrium, which was investigated in detail by variable-temperature (VT) NMR spectroscopy supported by density-functional theory (DFT) calculations. Depending on the substituents, two phosphaalkene derivatives and ten acylphosphine derivatives could be isolated. NMR spectroscopy and single-crystal X-ray crystallography enabled a clear structural assignment of these compounds. Oxidation of selected TAPs led to the formation of the corresponding tris(acyl)phosphine oxides (TAPOs). Furthermore, their spectroscopic properties as well as their photochemistry was investigated. Especially, the TAPO compounds were evaluated for their suitability as photoinitiators by CIDNP spectroscopy, photobleaching measurements and by storage stability tests.

Interactions and characterization of Zein-BSA nanoparticles: Multi-spectral analysis and molecular simulations

Zein-bovine serum albumin (BSA) nanoparticles (NPs) with varying mass ratios were prepared via anti-solvent precipitation method at pH 4.0. Zein-BSA NPs at high Zein mass ratios exhibited superior particle characteristics and surface morphology. Ultraviolet-visible, fluorescence, and X-ray diffraction analyses demonstrated the formation and conformational transition during the binding of Zein and BSA, while ANS hydrophobic binding, fourier transform infrared spectra, and circular dichroism confirmed the hydrophobic exposure and secondary structure assignment. Molecular dynamic simulations revealed that Zein spontaneously bound to the IIB domain of BSA with a binding free energy of −63.52 ± 6.37 kcal/mol, which was dominated by hydrophobic and electrostatic interactions, supplemented by hydrogen bonds. Dissociation experiments supported the key role of hydrophobic and electrostatic interactions in maintaining the stability of the NPs. These findings provided insights into the formation and stabilization mechanisms of Zein-BSA NPs, and their potential applications as encapsulation carriers for bioactive substances or as novel nanoscale food substrates.

Synthesis, structures, electrochemical characterizations, theoretical and anticancer studies of Pd(II)-, Pt(II)- NHC complexes

We present the synthesis of two novel cationic Pd(II)- and Pt(II)- complexes ligated to a new C ∩ N donor N-heterocyclic carbene (NHC) ligand 3-methyl-1-(1-methyl-2-methylbenzoyl)imidazolin-2-ylidene, (1). Capitalizing 3-methyl-1-(1-methyl-2-methylbenzoyl)imidazolium hexafluorophosphate (1.HPF6), two novel isoelectronic and isostructural [Pd(1)2][PF6]2 (2), and [Pt(1)2][PF6]2 (3) complexes were synthesized. All the compounds were characterized by elemental analysis, 1H NMR, 13C NMR, IR, UV–Vis, mass spectroscopic studies, and finally single-crystal X-ray studies. X-ray crystallographic studies revealed both complexes 2 and 3 adopted square planar geometry. Electrochemical studies revealed Pt(II)/Pt(IV) reversible redox potential at 0.52 V. The catalytic activity of Pd(II)–NHC complex, 2 was tested for Suzuki coupling reactions. The structural assignments were further supported by DFT calculations. Molecular docking studies show a better binding affinity of 3 with Human-DNA Topoisomerase and BCL-2 protein compared to 2 and the scope of the complex 2 and 3 may be used as a drug. Cytotoxicity studies revealed that Pt(II)–NHC complex 3 is more potent than Pd(II)–NHC complex 2 against the breast cancer cell line (MCF-7) (IC50,7.9 ± 0.84 vs 6.0 ± 0.72 μM).

Valence and Rydberg excitations of 3-fluorotoluene in the 4.4–10.8 eV photoabsorption energy region

The absolute photoabsorption cross sections for 3-fluorotoluene in the 4.4–10.8 eV energy-range were obtained for the first-time using a synchrotron radiation light source. New theoretical calculations, providing vertical excitation energies and oscillator strengths, were performed at the time-dependent density functional theory and the equation-of-motion coupled cluster method restricted to single and double excitations to qualitatively support the experimental data. The electronic transitions discernible in the photoabsorption spectrum have been assigned to valence, mixed valence-Rydberg and Rydberg transitions. Additionally, a comprehensive assignment of the vibronic structure was performed with the main contribution of C–H in plane bending mode progressions dictating the spectroscopy of the lowest-lying absorption band. From the absolute photoabsorption cross sections, the photolysis lifetimes of 3-fluorotoluene in the Earth's atmosphere were also obtained.

Precursor-Directed Biosynthesis and Biological Testing of omega-Alicyclic- and neo-Branched Tunicamycin N-Acyl Variants.

Tunicamycins (TUNs) are Streptomyces-derived natural products, widely used to block protein N-glycosylation in eukaryotes or cell wall biosynthesis in bacteria. Modified or synthetic TUN analogues that uncouple these activities have considerable potential as novel mode-of-action antibacterial agents. Chemically modified TUNs reported previously with attenuated activity on yeast have pinpointed eukaryotic-specific chemophores in the uridyl group and the N-acyl chain length and terminal branching pattern. A small molecule screen of fatty acid biosynthetic primers identified several novel alicyclic- and neo-branched TUN N-acyl variants, with primer incorporation at the terminal omega-acyl position. TUNs with unique 5- and 6-carbon ω-cycloalkane and ω-cycloalkene acyl chains are produced under fermentation and in yields comparable with the native TUN. The purification, structural assignments, and the comparable antimicrobial properties of 15 of these compounds are reported, greatly extending the structural diversity of this class of compounds for potential medicinal and agricultural applications.

A Biomimetic Stereoselective Approach to Euolutchuol C and Its Structural Assignment

AbstractThe first stereoselective total synthesis of euolutchuol C using a biomimetic cationic polyene cyclization is demonstrated, and its absolute structure has been established. Four potential stereoisomers of euolutchuol C were synthesized to confirm the structure as an aromatic abietane diterpenoid consisting of 15(S)‐stereogenic center. Asymmetric Sharpless dihydroxylation was employed to construct the chiral epoxide, while CBS‐reduction was utilized for enantiomerically pure benzylic alcohols. A convergent approach is used to synthesize euolutchuol C in seven longest linear steps to give an overall yield of 23 %.

Measurement of Angle Between Subspaces in Direct Sum Decomposition

The problems of Eigen structure assignment has been studied. As an immediate part of that, the problem addressed is the development of measures of “skewness” between subspaces which are in the direct sum decomposition of the state space and a concept of angle between a set of subspaces.

A molecular networking-assisted automatic database screening strategy for comprehensive annotation of small molecules in complex matrices

Liquid chromatography-tandem with high-resolution mass spectrometry (LCHRMS) has proven challenging for annotating multiple small molecules within complex matrices due to the complexities of chemical structure and raw LCHRMS data, as well as limitations in previous literatures and reference spectra related to those molecules. In this study, we developed a molecular networking assisted automatic database screening (MN/auto-DBS) strategy to examine the combined effect of MS1 exact mass screening and MS2 similarity analysis. We compiled all previously reported compounds from the relevant literatures. With the development of a Python software, the in-house database (DB) was created by automatically calculating the m/z and data from experimental MS1 hits were rapid screened with DB. We then performed a feature-based molecular network analysis on the auto-MS2 data for supplementary identification of unreported compounds, including clustered FBMN and annotated GNPS compounds. Finally, the results from both strategies were merged and manually curated for correct structural assignment. To demonstrate the applicability of MN/auto-DBS, we selected the Huangqi-Danshen herb pair (HD), commonly used in prescriptions or patent medicines to treat diabetic nephropathy and cerebrovascular disease. A total of 223 compounds were annotated, including 65 molecules not previously reported in HD, such as aromatic polyketides, coumarins, and diarylheptanoids. Using MN/auto-DBS, we can profile and mine a wide range of complex matrices for potentially new compounds.

Use of customized 3-dimensional printed mandibular prostheses with a dental implant pressure-reducing device in mandibular body defect: A finite element study performing multiresponse surface methodology

Background/purposeSegmental body defects of the mandible result in the complete loss of the affected region. In our previous study, we investigated the clinical applicability of a customized mandible prosthesis (CMP) with a pressure-reducing device (PRD) in an animal study. In this study, we further incorporated dental implants into the CMP and explored the use of dental implant PRD (iPRD) designs. Materials and methodsBy employing a finite element analysis approach, we created 4 types of CMP: CMP, CMP with iPRD, CMP-PRD, and CMP-PRD with iPRD. We developed 2 parameters for the iPRD: cone length (CL) in the upper part and spring pitch (SP) in the lower part. Using the response surface methodology (RSM), we determined the most suitable structural assignment for the iPRD. ResultsOur results indicate that CMP-PRD had the highest von Mises stress value for the entire assembly (1076.26 MPa). For retentive screws and abutments, CMP with iPRD had the highest von Mises stress value (319.97 and 452.78 MPa, respectively). CMP-PRD had the highest principal stress (131.66 MPa) in the anterior mandible. The iPRD reduced principal stress in both the anterior and posterior mandible. Using the RSM, we generated 25 groups for comparison to achieve the most favorable results for the iPRD and we might suggest the CL to 12 mm and the SP to 0.4 mm in the further clinical trials. ConclusionUse of the PRD and iPRD in CMP may resolve the challenges associated with CMP, thereby promoting its usage in clinical practice.