Theoretical analysis of somatostatin receptor 5 with antagonists and agonists for the treatment of neuroendocrine tumors

We report on SSTR5 receptor modeling and its interaction with reported antagonist and agonist molecules. Modeling of the SSTR5 receptor was carried out using multiple templates with the aim of improving the precision of the generated models. The selective SSTR5 antagonists, agonists and native somatostatin SRIF-14 were employed to propose the binding site of SSTR5 and to identify the critical residues involved in the interaction of the receptor with other molecules. Residues Q2.63, D3.32, Q3.36, C186, Y7.34 and Y7.42 were found to be highly significant for their strong interaction with the receptor. SSTR5 antagonists were utilized to perform a 3D quantitative structure–activity relationship study. A comparative molecular field analysis (CoMFA) was conducted using two different alignment schemes, namely the ligand-based and receptor-based alignment methods. The best statistical results were obtained for ligand-based (\({q}^{2} = 0.454\), \({r}^{2}\) = 0.988, noc = 4) and receptor-guided methods (docked mode 1:\({q}^{2} = 0.530\), \({r}^{2} = 0.916\), noc = 5), (docked mode 2:\({q}^{2}\) = 0.555, \({r}^{2 }= 0.957\), noc = 5). Based on CoMFA contour maps, an electropositive substitution at \(\hbox {R}^{1}\), \(\hbox {R}^{2}\) and \(\hbox {R}^{4}\) position and bulky group at \(\hbox {R}^{4}\) position are important in enhancing molecular activity.     

Neutron and proton shell closure in the superheavy region via cluster radioactivity in <Superscript>280–314</Superscript>116 isotopes

Based on the concept of cold valley in fission and fusion, the radioactive decay of superheavy^280–314116 nuclei was studied taking Coulomb and proximity potentials as the interacting barrier. It is found that the inclusion of proximity potential does not change the position of minima but minima become deeper which agrees with the earlier findings of Gupta and co-workers. In addition to alpha particle minima, the other deepest minima occur for ⁸Be, ^12,14C clusters. In the fission region two deep regions are found each consisting of several comparable minima, the first region centred on ²⁰⁸Pb and the second is around ¹³²Sn. The cluster decay half-lives and other characteristics are computed for various clusters ranging from alpha particle to ⁷⁰Ni. The computed half-lives for alpha decay match with the experimental values and with the values calculated using Viola-Seaborg-Sobiczewski (VSS) systematic. The plots connecting computed Q values and half-lives against neutron number of daughter nuclei were studied for different clusters and it is found that the next neutron shell closures occur at N = 162, 172 and 184. Isotopic and isobaric mass parabolas are studied for various cluster emissions and minima of parabola indicate neutron shell closure at N = 162, 184 and proton shell closure at Z = 114. Our study shows that ₁₆₂²⁷⁶114 is the deformed doubly magic and ₁₈₄²⁹⁸114 is the spherical doubly magic nuclei.      

Voltammetric determination of nitroaromatic and nitramine explosives contamination in soil

The contamination of soil by nitroaromatic and nitramine explosives is widespread during the manufacture, testing and disposal of explosives and ammunitions. The analysis for the presence of trace explosive contaminants in soil becomes important in the light of their effect on the growth of different varieties of plants and crops. 2,4,6-Trinitrotoluene (TNT), cyclotrimethylene trinitramine (Research Department explosive, RDX) and cyclotetramethylene tetranitramine (high melting point explosive, HMX), other related explosive compounds and their by-products must be monitored in soil and surrounding waterways since these are mutagenic, toxic and persistent pollutants that can leach from the contaminated soil to accumulate in the food chain. In this study, a voltammetric method has been developed for the determination of explosive such as RDX, HMX and TNT. The electrochemical redox behavior of RDX, HMX and TNT was studied through cyclic voltammetry and quantitative determination was carried out by using square wave voltammetry technique. Calibration curves were drawn and were linear in the range of 63-129 ppm for RDX with a detection limit of 10 ppm, 49-182 ppm for HMX with a detection limit of 1 ppm and 38-139 ppm for TNT with a detection limit of 1 ppm. This method was applied to determine the contaminations in several soil samples that yielded a relative error of 1% in the concentrations.     

Self-location of acceptors as "isolated" or "stacked" energy traps in a supramolecular donor self-assembly: a strategy to wavelength tunable FRET emission

Control over supramolecular assemblies of donor and acceptor arrays in nanoscale dimension that facilitate efficient energy transfer resulting in tunable emission is an outstanding challenge. In pursuit of this goal, we have designed a supramolecular donor-acceptor organogel with tunable emission from green to red through controlled energy transfer by simply varying the acceptor concentration. Temperature-dependent UV/vis absorption, XRD, and AFM studies of the coassembly of 1 (donor) and 2 (acceptor) revealed the intercalation of 2 within the self-assembly of 1. Upon excitation of the decane gels of 1 with 0-2 mol % of 2, quenching of the emission of the former at 509 nm with the formation of the monomer emission of the latter at 555 nm is observed. Upon further addition of 2 (2-20 mol %), the emission was continuously red-shifted to 610 nm, which corresponds to the aggregate emission of 2. Consequently, a 98% quenching of the donor emission was observed at 509 nm. Fluorescence microscopic studies provided visual evidence for the color tuning of the FRET emission. Thus efficient trapping of excitons by "isolated" or "aggregated" acceptors through a subtle control of the self-assembly and the photophysical properties of the donor-acceptor building blocks allowed a continuous shifting of the emission color anywhere between green and red (lambdamax, 509-610 nm) in a supramolecular light harvesting system.     

Synthesis of potential impurities of cloxacillin sodium drug substance

The present work describes the synthesis and characterization of six related compounds of cloxacillin sodium ( 1 ) viz penicilloic acid of cloxacillin (2) , (3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl) glycine (Glycine analogue of cloxacillin) (3), CMICAA adduct of cloxacillin (4) , (4S)-2-(carboxy(3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido) methyl)-3-(2-ethylhexanoyl)-5,5-dimethylthiazolidine-4-carboxylic acid (N-2-ethylhexanoyl penicilloic acid of cloxacillin) ( 5 ), N-Acetylated penicilloic acid of cloxacillin ( 6 ), and Cloxacillin Penicillamide (7) . These related compounds are very essential in the process development of cloxacillin sodium and are used as reference standards to determine the quality of the drug substance.     

A thermodynamic perspective of the metastability of holey sheets: the role of curvature

Producing nanostructures with high surface area that are stable is important to accomplish sustained use of catalytic materials in practical settings. Avoiding the processes of ripening and sintering that typically hinder stability has long been recognized as a significant challenge and much research is focused on addressing these issues. In this article, we investigate a Pt nanostructure-a holey nanosheet-that exhibits high surface area and stability. The findings from lattice gas simulations produce a stability diagram that relates a critical hole diameter to sheet thickness. The stability is now addressed from a thermodynamic point of view, and, in particular, the crucial role of curvature is considered. We find that the stability of certain sized holes is due to the near zero mean curvature of the surface of the holes and of the surrounding flat sheet. Molecular dynamics simulations of Pt (using an embedded atom potential) are reported for small nanoclusters and model holes in sheets to illustrate the strong effects of curvature on thermodynamic properties such as the lowering of melting and surface melting temperatures.     

Facile formation of five-membered N-heterocyclic zirconacycloallenoids

The reaction of η(2)-iminozirconocene chloride complexes with trimethylsilylethynyl lithium leads to rapid C-C coupling at room temperature to yield the corresponding five-membered aza-zirconacycloallenoids. Such compounds were also obtained by trapping of in situ generated zirconocene with alkynyl imines.     

Synthesis of thioether‐functional poly(olefin)s via ruthenium‐alkylidene initiated ring‐opening metathesis polymerization

Ring‐opening metathesis polymerization (ROMP) of thioether‐derived oxanorbornene imide ( M1 ) and its copolymerization with various cycloolefin comonomers such as cyclopentene ( M2 ), cyclopent‐3‐en‐1‐ol ( M3 ), cycloheptene ( M4 ), and cyclooctene ( M5 ) using Hoveyda–Grubbs second generation catalyst has been investigated. Polymerizations were performed at two different temperatures (0 and 25 °C) and the obtained functional poly(olefin)s were characterized by nuclear magnetic resonance ¹H and ¹³C (NMR), and infrared spectroscopy as well as size exclusion chromatography, differential scanning calorimetry, and thermogravimetric analysis analyses. Additionally, the dependence of the polymer composition on the reaction temperature and monomer feed was studied with time‐dependent ¹H NMR experiments. Copolymerization of M1 with a five‐membered cycloolefin monomer M2 showed relatively low ROMP reactivity irrespective of the reaction conditions in comparison to M3 , M4 , and M5 monomers. In general, the degree of monomer incorporation into poly(olefin)s were determined in the order of M5 > M3 > M4 > M2 , and that sheds light on the effect of cycloolefin ring strain energies in the ruthenium‐alkylidene initiated ROMP. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1741–1747     

HPLC Bioassay of Elvitegravir using a Molecularly Imprinted Polymer Based Solid Phase Extraction in RAT Plasma: Application to Pharmacokinetic Studies

Journal of Analytical Chemistry - A water-compatible molecularly imprinted polymer (MIP) was prepared for specific extraction of HIV-1 integrase inhibitor elvitegravir (EVG). It was prepared by a...     

The phenomenon of nucleon emission at high angular momentum states of fused compound systems

Nucleon emission from high spin fused compound systems is analyzed in the framework of the statistical theory of hot rotating (STHR) nuclei. This is an elaborate version of our earlier work and we present our results for¹⁵⁶Er,¹⁶⁶Er,¹⁶⁸ Yb and¹⁸⁸Hg. We predict an increase in neutron emission for¹⁶⁶Er due to the abrupt decrease in neutron separation energy aroundI ≈55ℏ. Since the drop in the separation energy is closely associated with the structural changes in the rotating nuclei, relative increase in neutron emission probability around certain values of angular momentum may be construed as evidence for the shape transition. A similar effect is predicted for¹⁶⁸Yb aroundI ≈55ℏ. We also extend the microscopic cranked Nilsson method (CNM) to hot nuclear systems and compare the results with that of the STHR method. The two methods yield different results for triaxially deformed nuclei although for biaxial deformations the results are identical. This is illustrated for¹⁸⁶Hg.