Crystal structures of two substituted key intermediates of phenothiazine derivatives

The key intermediates, in the synthesis of phenothiazines, 5-hydroxy-5-methyl 3(phenyl) 2,4-N-dimethylcarbamoyl cyclohexanone, C₁₇H₂₂O₄N₂ (I), and 5-hydroxy-5-methyl 3(2-methylphenyl) 2,4-N-dimethylcarbamoyl cyclohexanone, C₁₈H₂₄O₄N₂ (II), contain essentially substituted cyclohexanone rings in chair conformation with approximately perpendicular oriented phenyl rings. The carbamoyl groups are aligned in opposite directions to facilitate the formation of intramolecular C–HO interaction and O–HO hydrogen bonding. The molecules are linked in helical fashion by an N–HO type intermolecular hydrogen bonding framework. Crystal data: [I], orthorhombic, space group Pbca, a = 9.278(1), b = 19.094(2), c = 19.802(2) Å, V = 3508.0(6) ų, Z = 8 and d = 1.206 Mg m^–3, R = 0.074 (wR = 0.137) for 208 parameters and 1190 observed reflections with I 2 (I); [II], monoclinic, space group P2₁/n, a = 10.523(1), b = 9.005(1), c = 19.771(2) Å, = 94.96(6)°, V = 1866.5(3) ų, Z = 4 and d = 1.183 Mg m^–3, R = 0.062 (wR = 0.131) for 217 parameters and 2276 observed reflections with I 2 (I).     

Crystal and molecular structures of 1,4-dihydro-6-methyl-5-N,N-diethylcarbamoyl-4-phenyl-2(3H)-pyrimidinethione (1) and 1,4-dihydro-6-methyl-5-N-methyl carbamoyl-4-(2′-nitrophenyl)-2(3H)-pyrimidinethione hemihydrate (2)

The crystal structure of 1,4-dihydro-6-methyl-5-N,N-diethylcarbamoyl-4-phenyl-2(3H)-pyrimidinethione, C₁₆ H ₂₁ N ₃OS (1), is monoclinic, space group P2₁/n, a = 6.818(1), b = 13.211(2), c = 18.807(3) Å, = 99.53(1)°, V = 1670.6(4) ų, Z = 4 and d _cal = 1.206 Mg/m³, R = 0.042 (wR = 0.119) for 190 parameters and 2560 observations with I 2(I) and 1,4-dihydro-6-methyl-5-N-methyl carbamoyl-4-(2-nitrophenyl)-2(3H)-pyrimidinethione hemihydrate, C₁₃ H ₁₄N₄O₃S 0.5H₂O, (2), is triclinic, space group P1, a = 7.513(1), b = 14.381(2), c = 15.506(2)Å, = 114.95(2), = 98.11(1), = 93.55(1)°, V = 1490.0(3) ų, Z = 4 and d _cal = 1.406 Mg/m³, R = 0.062 (wR = 0.165) for 388 parameters and 3094 observations with I 2(I).The compound 2 crystallized having two molecules in the asymmetric unit, which can be regarded as monohydrated dimers, and forming a hydrate. The conformation of the central heterocyclic ring (1,4-dihydropyrimidine) in both compounds was found to be close to a half-chair conformation. The 2-nitrophenyl substituent in 2 is in the axial synperiplanar orientation. In both compounds, the conformation of the 3-substituted carbamoyl group appears to be influenced by hydrogen bonding with anticlinal orientation observed for carbonyl groups serving as hydrogen bonding acceptors.     

Inorganic hybrid nanoparticles in cancer theranostics: understanding their combinations for better clinical translation

Drug resistance, tumor heterogeneity, and poor selectivity make cancer treatment with current modalities a challenging and complicated task. Careful planning of diagnosis and therapy is required to build new strategies for treatment and management of cancer. The amalgamation of therapeutics and diagnostics in a single nano agent, known as theranostics is now possible due to the emergence of nanotechnology. Theranostics offers opportunities for personalized medicine by real-time monitoring of drug accumulation and dynamic modification of treatment depending on individual patient needs. Thus potential to reform disease management is held by theranostic nanoparticles. Amongst other nanosystems, inorganic nanoparticles have been widely used for developing theranostic drug delivery systems due to their favorable intrinsic properties. The last decade has seen a surge in development of such theranostic nanoparticles in which various inorganic materials in different combinations have been engineered to maximize the output with respect to specific applications. For example, Fe₃O₄@Au nanoparticles were developed for MRI, hyperthermia and magnetically controlled drug delivery. Several such combinations leading to innovative theranostic applications and their underlying mechanisms have been highlighted in this review. A review of patents and clinical trials of inorganic theranostic nanoparticles is also presented through which we understood that clinical translation still remains in the nascent stage. Thus, it is necessary to find and understand reasons for lack of clinical translations. Therefore, we have discussed the challenges associated with bench-to-bed translation of such inorganic nanoparticles which show immense potential in vitro but fail to deliver in long run.     

DEMULSIFICATION OF WATER IN OIL EMULSIONS USING WATER SOLUBLE DEMULSIFIERS

The possibility of using a water soluble,as opposed to the conventional oil soluble demulsifier, to destabilize a w/o emulsion in crude oil has been explored. It was found experimentally that a surfactant soluble in the water (dispersed) phase could destabilize the emulsion. Polymer molecules with varying HLB's and molecular weights and structure were synthesized and these compounds were added to the water phase to destabilize the water/crude oil emulsions. Molecules with a high percentage of hydrophilic groups and low molecular weights showed very good demulsifying abilities.     

Evaporation and fission decay of 132Ce compound nuclei at Ex=122 MeV: some limitations of the statistical model

Light charged particle (LCP) emission in the evaporation residue (ER) and fusion fission (FF) channels have been studied for the 200 MeV ³²S + ¹⁰⁰Mo reaction, leading to ¹³²Ce composite nuclei at E _x =122 MeV. The main goal was to study the decay of ¹³² Ce on the basis of an extended set of observables, to get insights on the fission dynamics. The proton and alpha particle energy spectra, their multiplicities, ER-LCP angular correlations, ER and FF angular distributions, and ER and FF cross-sections were measured. The measured observables were compared with the Statistical Model (SM). Using standard parameters, the model was able to reproduce only the pre-scission multiplicities and the FF and ER cross-sections. The calculation was observed to strongly overestimate the proton and alpha particle multiplicities in the ER channel. Disagreements were also observed for the ER-LCP correlations, the LCP energy spectra and the ER angular distribution. By varying the SM input parameters over a wide range of values, it is shown that it is not possible to reproduce all the observables simultaneously with a unique set of parameters. The inadequacy of the model in reproducing the ER particle multiplicities is also observed analysing data from the literature for other systems in the A ≈ 150 and E _x ≈ 100?200 MeV region. These results indicate serious limitations about the use of the SM in extracting information on fission dynamics.     

Enhanced production of neutron-rich rare isotopes in peripheral collisions at Fermi energies

A large enhancement in the production of neutron-rich projectile residues is observed in the reactions of a 25 MeV/nucleon 86Kr beam with the neutron-rich 124Sn and 64Ni targets relative to the predictions of the EPAX parametrization of high-energy fragmentation, as well as relative to the reaction with the less neutron-rich 112Sn target. A hybrid model based on a deep-inelastic transfer (DIT) code followed by a statistical deexcitation code accounts for part of the observed large cross sections. The DIT simulation indicates that the production of neutron-rich nuclides in these reactions is associated with peripheral nucleon exchange in which the neutron skins of the neutron-rich 124Sn and 64Ni target nuclei may play an important role. From a practical viewpoint, such reactions offer a novel synthetic avenue to access extremely neutron-rich rare isotopes towards the neutron-drip line.     

Depth profile study of natural radionuclides in the environment of coastal Kerala

The present work investigated the activity concentrations of natural radionuclides ²²⁶Ra, ²³²Th and ⁴⁰K in beach sand samples along coastal Kerala including high background radiation area. The activity of ²³²Th ranges from below detectable level to 23029.9 Bq kg⁻¹ with a mean value of 2660.2 Bq kg⁻¹ for 0–10 cm depth interval. For 10–20 cm depth, the ²³²Th activity ranged from below detectable to 4452.2 Bq kg⁻¹ with a mean value of 815.5 Bq kg⁻¹. The variation of ²²⁶Ra activity with depth is parallel with the ²³²Th activity distribution in beach sand. Its activity varied from below detectable to 5169.5 Bq kg⁻¹ with a mean value 487.6 Bq kg⁻¹ at 0–10 cm depth. For 10–20 cm depth interval, the ²²⁶Ra activity ranges from below detectable to 1823.6 Bq kg⁻¹ with a mean value 296.0 Bq kg⁻¹. Similarly the activity varies from below detectable to 1826.6 Bq kg⁻¹ with a mean value of 211.0 Bq kg⁻¹ for a depth interval of 20–30 cm. The activity of ⁴⁰K at different depth is also discussed. Statistical analysis of radioactivity was also carried out. The results of these investigations are presented in this paper.     

Electron spin resonance spectrum of a 5-membered cyclic alkoxy nitroxyl radical

The esr spectrum of a 5-membered cyclic alkoxy nitroxyl radical is reported. 20111979     

Identification and characterization of stressed degradation products of metoprolol using LC/Q-TOF-ESI-MS/MS and MS(n) experiments

A rapid, specific and reliable isocratic high-performance liquid chromatography combined with quadrupole time-of-flight electrospray ionization tandem mass spectrometry (LC/Q-TOF-ESI-MS/MS) method has been developed and validated for the identification and characterization of stressed degradation products of metoprolol. Metoprolol, an anti-hypertensive drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per ICH-specified conditions. The drug showed extensive degradation under oxidative and hydrolysis (acid and base) stress conditions. However, it was stable to thermal, neutral and photolysis stress conditions. A total of 14 degradation products were observed and the chromatographic separation of the drug and its degradation products was achieved on a C(18) column (4.6 × 250 mm, 5 μm). To characterize degradation products, initially the mass spectral fragmentation pathway of the drug was established with the help of MS/MS, MS(n) and accurate mass measurements. Similarly, fragmentation pattern and accurate masses of the degradation products were established by subjecting them to LC-MS/QTOF analysis. Structure elucidation of degradation products was achieved by comparing their fragmentation pattern with that of the drug. The degradation products DP(2) (m/z 153) and DP(14) (m/z 236) were matched with impurity B, listed in European Pharmacopoeia and British Pharmacopoeia, and impurity I, respectively. The LC-MS method was validated with respect to specificity, linearity, accuracy and precision.