Functionalized SBA-15 and its Catalytic Applications in Selective Organic Transformations

Ordered, mesoporous SBA-15 functionalized with organic and inorganic moieties exhibits efficient catalytic activity in a variety of organic transformations. In this account, reviewing our own work, three-sets of surface-modified SBA-15 materials have been investigated. The first-set of materials consists of SBA-15 modified with organo-acidic (propyl thiol and propyl sulfonic acid) and basic (propyl amine and propyl adenine) moieties. The second-set of materials was prepared by grafting Mn complexes to the organo-functionalized SBA-15. The third-set composes of nanocrystalline metal oxides supported on SBA-15. All these catalysts have been characterized by structural and spectroscopic techniques. Catalytic activities of the first-set of solid materials have been investigated in acid/base-catalyzed reactions viz., ring-opening of epoxides with amines (producing β-amino alcohols), esterification, three-component-Mannich reactions and cycloaddition of CO₂ to epoxides. The Mn complexes grafted on organofunctionalized SBA-15 are efficient catalysts for the chemo-, regio- and stereoselective aerial oxidation of monoterpenes at ambient conditions. TiO_x, VO_x, MoO_x and WO_x supported on SBA-15 catalyzed biomimetic oxyhalogenation of aromatic compounds. In all these reactions, the functionalized SBA-15 showed high selectivity.     

WEB-spline based mesh-free finite element analysis for the approximation of the stationary Navier–Stokes problem

The objective in this paper is to discuss the existence and the uniqueness of a weighted extended B$B$-spline (WEB-spline) based discrete solution for the stationary incompressible Navier–Stokes equations. The WEB-spline discretization is newly developed methodology which satisfies the inf–sup condition or Ladyshenskaya–Babus?ka–Brezzi (LBB) condition. The main advantage of these new elements over standard finite elements is that they use regular grids instead of irregular partitions of the domain, thus eliminating the difficult and time-consuming pre-processing step. An error estimate for this WEB-spline based discrete solution is also obtained.     

Development and validation of a sensitive LC-MS/MS method with electrospray ionization using multiple ions for quantitation of torcetrapib in hamster and dog plasma

A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of torcetrapib (TTB) with 100 microL hamster/dog plasma using DRL-16126 as an internal standard (IS). The API-4000 Q Trap LC-MS/MS was operated under multiple-reaction monitoring mode using the electrospray ionization technique. The assay procedure involved extraction of TTB and IS from plasma with acetonitrile, which yielded consistent recoveries of 65.73 and 94.01% for TTB and 79.68 and 90.70% for IS in hamster and dog plasma, respectively. The total chromatographic run time was 3.0 min and the elution of TTB and IS occurred at approximately 2.25 and 2.20 min, respectively. The resolution of peaks was achieved with 0.01 m ammonium acetate:acetonitrile (15:85, v/v) at a flow rate of 0.40 mL/min on an Inertsil ODS-3 column. The method was proved to be accurate and precise at linearity range of 1.00-200 ng/mL with a correlation coefficient (r) of > or = 0.993. The method was rugged with 1.00 ng/mL as the lower limit of quantitation. TTB was stable in the battery of stability studies. The application of the assay to preclinical pharmacokinetic studies confirmed the utility of the assay to derive hamster/dog pharmacokinetic parameters.     

Expeditious method for the synthesis of novel 2,3,5,6-tetrahydrobenzo[g][1,3,5]oxadiazocine-4-thiones linked with isoxazole

Synthesis of novel 3-ary1-5-(3,5-dimethylisoxazol-4-y1)-2,3,5,6-tetrahydrobenzo[g][1,3,5]oxadiazocine-4-thiones 5 has been accomplished from 3,5-dimethylisoxazol-4-amine I by condensation with salicylaldehydes, followed by reduction, treatment with aryl isothiocyanates and subsequent smooth ring closure via acetal formation in the presence of formaldehyde.     

Ultrafast intramolecular charge transfer with strongly twisted aminobenzonitriles: 4-(di-tert-butylamino)benzonitrile and 3-(di-tert-butylamino)benzonitrile

The newly synthesized aminobenzonitriles with two bulky amino substituents 4-(di-tert-butylamino)benzonitrile (DTABN) and 3-(di-tert-butylamino)benzonitrile (mDTABN) have strongly twisted amino groups in the ground state. From X-ray crystal analysis it is found that the amino twist angle theta of mDTABN equals 86.5 degrees , whereas a twist angle of around 75 degrees is deduced for DTABN from the extinction coefficient of its lowest-energy absorption band in n-hexane. Because of the electronic decoupling between the amino and benzonitrile groups caused by these large twist angles, the absorption of DTABN and mDTABN is relatively weak below 40000 cm-1, with extinction coefficients around 25 times smaller than those of the planar 4-(dimethylamino)benzonitrile (DMABN). DTABN as well as mDTABN undergo efficient intramolecular charge transfer (ICT) in the singlet excited state, in nonpolar (n-hexane) as well as in polar (acetonitrile) solvents. Their fluorescence spectra consist of an ICT emission band, without evidence for locally excited (LE) fluorescence. The occurrence of efficient ICT with mDTABN is different from the findings with all other N,N-dialkylaminobenzonitriles in the literature, for which ICT only appears with the para-derivative. From solvatochromic measurements, an ICT dipole moment of 17 D is determined for DTABN as well as for mDTABN, similar to that of DMABN. The picosecond fluorescence decays of DTABN (time resolution 3 ps) are effectively single exponential. Their decay time is equal to the ICT lifetime tau'0(ICT), which increases with solvent polarity from 0.86 ns in n-hexane to 3.48 ns in MeCN at 25 degrees C. The femtosecond excited-state absorption (ESA) spectra of DTABN in n-hexane and MeCN at 22 degrees C show a decay of the LE and a corresponding rise of the ICT absorption. The ICT reaction time is 70 fs in n-hexane and 60 fs in MeCN. DTABN and mDTABN may have a strongly twisted ICT state, similar to that of 6-cyanobenzoquinuclidine but different from that of DMABN.     

Stability indicating RP-HPLC method development and validation for oseltamivir API

The present study describes the development and subsequent validation of a stability indicating reverse-phase HPLC (RP-HPLC) method for the analysis of oseltamivir active pharmaceutical ingredient (API). The proposed RP-HPLC method utilizes Kromasil C(18), 5 microm, 250 mm x 4.6 mm i.d. column (at ambient temperature), gradient run (using acetonitrile and triethylamine as mobile phase), effluent flow rate (1.0 ml/min), and UV detection at 215 nm for analysis of oseltamivir. The described method was linear over the range of 70-130 microg/ml (r(2)=0.999). The precision, ruggedness and robustness values were also within the prescribed limits (<1% for system precision and <2% for other parameters). Oseltamivir was exposed to acidic, basic, oxidative and thermal stress conditions, and the stressed samples were analyzed by the proposed method. Chromatographic peak purity results indicated the absence of co-eluting peaks with the main peak of oseltamivir, which demonstrated the specificity of assay method for estimation of oseltamivir in presence of degradation products. The proposed method can be used for routine analysis of oseltamivir in quality control laboratories.     

Study of Forced Degradation Behaviour of Brinzolamide Using LC–ESI–Q-TOF and In Silico Toxicity Prediction

Brinzolamide (BZA) is a topical ophthalmic drug which is generally used to lower the intraocular pressure during glaucoma. It was subjected to forced degradation studies under hydrolytic (acidic, basic), oxidative, photolytic and thermal stress conditions; the drug degraded significantly in hydrolytic and oxidative conditions, leading to the formation of seven degradation products in total. It was stable on exposure to light and dry heat in the solid state. An ultra-performance liquid chromatography (UPLC) method was developed on a Waters CSH phenyl hexyl column (100 × 2.1 mm, 1.7 µm), using gradient elution of 0.1 % formic acid and methanol as mobile phase. The method was extended to quadrupole time-of-flight mass spectrometry (Q-TOF–MS) for the structural characterisation. All degradation products were comprehensively characterised by UHPLC–ESI/MS/MS experiments. The most probable mechanisms for the formation of degradation products were also proposed. In silico toxicity of the drug and its degradation products was determined using TOPKAT toxicity prediction software.

     

Synthesis and Cytotoxicity Evaluation of Novel Andrographolide‐1,2,3‐Triazole Derivatives

A series of new andrographolide‐1,2,3‐triazole derivatives, 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , were synthesized from a natural bioactive labdane type diterpenoid, andrographolide. All the derivatives were screened against human cancer cell lines MCF7, MDA‐MB‐231, COLO205, HepG2, K562, Hela, and HEK293 to evaluate their cytotoxic activity. All the compounds showed anticancer activity selectively against K562 cell line, with IC₅₀ values ranging from 8.00 to 17.11 µM, and are inactive against the rest of the cell lines. Compounds 3c and 3d showed significant cytotoxicity among the synthesized derivatives. The in silico docking studies revealed compounds 3b and 3d with high binding affinity against the cancer target, transient receptor potential vanilloid 1.