Amarinder Singh

Phosphine free SBA-15–EDTA–Pd highly active recyclable catalyst: synthesis characterization and application for Suzuki and Sonogashira reaction

Phosphine obstructed highly efficient and reusable SBA-15–EDTA–Pd(11) has been synthesized by anchoring a Pd–EDTA complex over the surface of organo-functionalized SBA-15. The physiochemical properties of the organo-functionalized catalyst were analyzed by elemental analysis, ICP-OES, XRD, N2 sorption measurement isotherms, TGA and DTA, solid state 13C, 29Si NMR spectroscopy FT-IR, XPS DRS UV-visible, SEM and TEM. The XRD and N2 sorption analyses of the synthesized catalyst confirm that the ordered mesoporous channel structure was retained even after the multistep synthetic procedures. The (100), (110) and (200) reflections in SBA-15 provide a good structural stability, an the existence of a long range order and high pore wall thickness. The TGA-DTA results reveal that the thermal stability of the synthesized catalyst SBA-15–EDTA–Pd(11) was maintained at higher temperature. The organic moieties anchored over the surface of the SBA-15 and inside the pore wall were demonstrated by solid state 13C NMR and FT-IR spectroscopy. Further, solid state 29Si NMR spectroscopy provides information about the degree of functionalization of the surface silanol groups, of the SBA-15 with organic moieties. The electronic environment and oxidation state of the Pd metal in the SBA-15–EDTA–Pd(11) were monitored by XPS, and DRS UV-visible techniques. Moreover, the morphologies and topographic information of the synthesized catalyst were confirmed by SEM and TEM spectroscopy. The synthesized catalyst SBA-15–EDTA–Pd(11) was screened for the Suzuki and Sonogashira coupling reactions and shows a higher catalytic activity with higher TON (turn over number). The anchored solid catalyst can be recycled efficiently and reused five times, without a major loss in the reactivity.

Synthesis and characterization of 3-[N,N′-bis-3-(salicylidenamino)ethyltriamine] Mo(VI)O2@SBA-15: a highly stable and reusable catalyst for epoxidation and sulfoxidation reactions

The efficient and reusable oxidation catalyst 3-[N,N′-bis-3-(salicylidenamino)ethyltriamine] Mo(VI)O2@SBA-15 has been synthesized by the anchoring of the 3-[N,N-bis-3-(salicylidenamino)ethyltriamine] ligand (L or Salpr) on the inner surfaces of organofunctionalized SBA-15 and subsequent complexation with Mo(VI)O2(acac)2. The physico-chemical properties of the functionalized catalysts were analyzed by elemental analysis, ICP-OES, XRD, N2-sorption measurements, TG & DTA, solid state 13C, 29Si NMR spectroscopy, FT-IR, Raman spectroscopy, XPS, DRS UV-Vis spectroscopy, SEM and TEM. XRD and N2 sorption analyses helped to find out the morphological and textural properties of the synthesized catalysts and confirm that an ordered mesoporous channel structure was retained even after the multistep synthetic procedures. The (100), (110) and (200) reflections in SBA-15 provide hints of a good structural stability, the existence of long range ordering and a high pore wall thickness. TG and DTA results reveal that the thermal stability of (L)Mo(VI)O2@SBA-15 was maintained up to 300 °C. The organic moieties anchored over the surface of the SBA-15 support were determined by solid state 13C NMR and FT-IR spectroscopy. Further, solid state 29Si NMR spectroscopy provides the information about the degree of functionalization of the surface silanol groups with the organic moiety. The electronic environment and the oxidation state of the molybdenum site in (L)Mo(VI)O2@SBA-15 were monitored by Raman spectroscopy, XPS and DRS UV-Vis techniques. Moreover, the morphology and topographic information of the synthesized catalysts were confirmed by SEM and TEM imaging. The synthesized catalysts were evaluated in epoxidation and sulfoxidation reactions, and the results show that (L)Mo(VI)O2@SBA-15 exhibits high conversion and selectivity towards epoxidation and sulfoxidation reactions in combination with high stability. The anchored solid catalysts can be recycled effectively and reused several times without major loss in activity. In addition, Sheldons hot filtration test was also carried out.

A covalently anchored 2,4,6-triallyloxy-1,3,5-triazine Pd(II) complex over a modified surface of SBA-15: catalytic application in hydrogenation reaction

Highly efficient and reusable SBA-15–TAT–Pd(II) has been synthesized by anchoring a 2,4,6-triallyloxy-1,3,5-triazine (TAT) complex over the organo-functionalized surface of SBA-15. The physiochemical properties of the organo-functionalized catalyst were analyzed by elemental analysis, ICP-OES, XRD, N2 sorption measurement isotherm, TGA & DTA, solid state 13C, 29Si NMR spectra, FT-IR, XPS, DRS UV-visible, SEM and TEM. XRD & N2 sorption were analyzed to find out the textural properties of the synthesized catalyst and confirm that an ordered mesoporous channel structure was retained even after the multistep synthetic procedures. The electronic environment and oxidation state of Pd in SBA-15–TAT–Pd(II) were monitored by XPS and DRS UV-visible techniques. The catalytic activity of the synthesized catalyst SBA-15–TAT–Pd(II) was screened for hydrogenation reactions and shows higher catalytic activity with good turnover numbers (TON) under optimized experimental conditions with maximum conversion (>99%) and selectivity (100%). The anchored solid catalyst can be recycled efficiently and reused upto five times without major loss in reactivity.

Synthesis of a recyclable and efficient Pd(II) 4-(2-pyridyl)-1,2,3-triazole complex over a solid periodic mesoporous organosilica support by “click reactions” for the Stille coupling reaction

A highly efficient, reusable B-PMO-TZ-Pd(II) catalyst was synthesized by anchoring 4-(2-pyridyl)-4-(2-pyridyl)-1,2,3-triazole ligand over the surface of an organo-functionalized benzene support containing periodic mesoporous organosilica (B-PMO) via “click reaction” and the subsequent complexation with PdCl2. B-PMO materials with uniform hexagonal arrangements were prepared using C16 alkyl trimethyl ammonium bromide [CTAB] surfactant under basic conditions. The physiochemical properties of the functionalised catalyst were analysed by elemental analysis, ICP-OES, XRD, N2 sorption, TGA & DTA, solid state 13C, 29Si NMR spectra, FT-IR, XPS, UV-vis, SEM and TEM. XRD and N2 sorption revealed the morphological and textural properties of the synthesized catalyst, confirming that ordered mesoporous channel structure was retained even after the multistep synthetic procedure. The (100), (110) and (200) reflections in B-PMO are evidence of its good structural stability and the existence of long range order. The TGA-DTA results reveal that the synthesized catalyst B-PMO-TZ-Pd(II) was thermally stable, even at high temperature. The organic moieties anchored over the surface of B-PMO were demonstrated by solid state 13C NMR and FT-IR spectroscopy. Solid state 29Si NMR spectroscopy provides information about the degree of functionalization of the surface silanol group. The electronic environment and oxidation state of Pd in B-PMO-TZ-Pd(II) were monitored by XPS and UV-visible techniques. Moreover, the morphologies and topographic information of the synthesized B-PMO-TZ-Pd(II) catalyst were confirmed by SEM and TEM analyses. The catalytic properties of the catalyst for the Stille coupling reaction were screened, and higher catalytic activities with high TONs were observed. The anchored solid B-PMO-TZ-Pd(II) catalyst can be recycled efficiently and reused several (four) times without a major loss in reactivity.

Pyrano-isochromanones as IL-6 inhibitors: synthesis, in vitro and in vivo antiarthritic activity.

Bergenin (1), a unique fused C-glycoside isolated from Bergenia species, possesses interesting anti-inflammatory and antipain activities. To study SAR of this scaffold, first-generation derivatives were synthesized and evaluated for inhibition of lymphocyte proliferation and production of pro-inflammatory cytokines. The C-7 substituted derivatives showed inhibition of IL-6 as well as TNF-α production. Bergenin and its most potent IL-6 inhibitor derivatives 4e and 4f were then investigated in a panel of in vitro and in vivo inflammation/arthritis models. These compounds significantly decreased the expression of NF-kB and IKK-β in THP-1 cells. In in vivo study in BALB/c mice, a dose-dependent inhibition of SRBC-induced cytokines, reduction in humoral/cell-mediated immunity, and antibody titer was observed. The CIA study in DBA/1J mice indicated that compounds led to reduction in swelling of paws, cytokine levels, and anticollagen IgG1/IgG2a levels. The significant in vivo immunosuppressive efficacy of pyrano-isochromanones demonstrates the promise of this scaffold for development of next-generation antiarthritic drugs.

Long-circulatory nanoparticles for gemcitabine delivery: Development and investigation of pharmacokinetics and in-vivo anticancer efficacy

The anticancer potential of gemcitabine, a nucleoside analog, is compromised due to the enzymatic degradation into inactive form leading to the short half-life in systemic circulation. Novel delivery strategies are required to improve therapeutic efficacy of this potential drug. Monomethoxy polyethylene glycol amine-polylactide-co-glycolide (mPEG-PLGA) co-polymer was synthesized and characterized by FTIR and (1)H NMR. Gemcitabine loaded mPEG-PLGA nanoparticles (NPs) were developed and investigated for pharmacokinetic profile and in vivo anticancer activity. The mPEG-PLGA NPs (size: 267±10nm, zeta potential: -17.5±0.2mV) exhibited sustained drug release profile and were found to be compatible with blood. The mPEG-PLGA NPs were able to evade the uptake by macrophages (i.e. THP-1 and J774A) by reducing the adsorption of proteins on the surface of NPs. The enhanced cellular uptake and cell cytotoxicity was observed by mPEG-PLGA NPs in MiaPaCa-2 and MCF-7 cells. The half-life of gemcitabine in mPEG-PLGA NPs was remarkably enhanced (19 folds) than native gemcitabine. Further, the pharmacokinetic modulation of gemcitabine using mPEG-PLGA-NPs was translated in improved anticancer efficacy as compared to native gemcitabine in Ehrlich ascites bearing Balb-c mice. The results demonstrated the potential of long-circulatory nanoparticles in improving the pharmacokinetic profile and in-turn the anticancer efficacy of gemcitabine.

Acute, sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.

PLGA nanoparticles augmented the anticancer potential of pentacyclic triterpenediol in vivo in mice

A pentacyclic triterpenediol (TPD) from Boswellia serrata exhibited a good anticancer potential preclinically, however, it has low aqueous solubility and high lipophilicity, which therefore, necessitate suitable formulation development for in vivo application. In the present study TPD-loaded PLGA nanoparticles (TPD NPs) were prepared by an emulsion–diffusion–evaporation technique which exhibited an average particle size in the order of about 161 nm as confirmed by dynamic light scattering (DLS) and atomic force microscopy (AFM). The thermal analysis confirms that the TPD was entrapped into the NPs in an amorphous form. In vitro cell culture experiments indicated higher cellular cytotoxicity of the TPD-loaded NPs over free TPD in MCF-7 and OVCAR-5 cells. The higher cytotoxicity of TPD NPs was attributed to enhanced cellular apoptosis, loss of membrane potential and generation of high reactive oxygen species (ROS). The TPD-loaded NPs demonstrated a significantly higher in vivo anticancer potential as compared to TPD solution in the Ehrlich ascites tumor (EAT) model following intraperitoneal administration. Furthermore, no hematological and biochemical toxicity in EAT bearing mice was observed after the treatment. The results showed that the developed PLGA-NPs could be a potential option for improved TPD delivery in cancer chemotherapy.

Phenylacetylene hydrogenation on Au@Ni bimetallic core–shell nanoparticles synthesized under mild conditions

The synthesis of Au@Ni bimetallic core–shell nanoparticles through an energy efficient (lower temperature) route in oleylamine following a sequential reduction strategy is reported. The method is found to be useful for the synthesis of a very thin nickel shell (2 nm) over a gold core (15 nm). Synergistic effects are observed in catalyzing phenylacetylene hydrogenation under different solvent conditions.

Development and evaluation of long-circulating nanoparticles loaded with betulinic acid for improved anti-tumor efficacy

The clinical application of betulinic acid (BA), a natural pentacyclic triterpenoid with promising antitumor activity, is hampered due to its extremely poor water solubility and relatively short half-life in the systemic circulation. In order to address these issues, herein, we developed betulinic acid loaded polylactide-co-glycolide- monomethoxy polyethylene glycol nanoparticles (PLGA-mPEG NPs). The PLGA-mPEG co-polymer was synthesized and characterized using NMR and FT-IR. BA loaded PLGA-mPEG NPs were prepared by an emulsion solvent evaporation method. The developed nanoparticles had a desirable particle size (∼147nm) and exhibited uniform spherical shape under transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The PLGA-mPEG NPs were able to decrease the uptake by macrophages (i.e. J774A.1 and Raw 264.7 cells) as compared to PLGA nanoparticles. In vitro cytotoxicity in MCF7 and PANC-1 cells demonstrated enhanced cytotoxicity of BA loaded PLGA-mPEG NPs as compared to free BA. The cellular uptake study in both the cell lines demonstrated time dependent uptake behavior. The enhanced cytotoxicity of BA NPs was also supported by increased cellular apoptosis, mitochondrial membrane potential loss, generation of high reactive oxygen species (ROS) and cell cycle arrest. Further, intravenous pharmacokinetics study revealed that BA loaded PLGA-mPEG NPs could prolong the circulation of BA and remarkably enhance half-life by ∼7.21 folds. Consequently, in vivo studies in Ehrlich tumor (solid) model following intravenous administration demonstrated superior antitumor efficacy of BA NPs as compared to native BA. Moreover, BA NPs treated Ehrlich tumor mice demonstrated no biochemical, hematological and histological toxicities. These findings collectively indicated that the BA loaded PLGA-mPEG NPs might serve as a promising nanocarrier for improved therapeutic efficacy of betulinic acid.