Selective Oxidation of Glycerol via Acceptorless Dehydrogenation Driven by Ir(I)-NHC Catalysts

After pandemic, healthcare workers experienced a series of emotional and psychological disturbances that could impact their mental well-being. In this study, the feasibility of morphological characteristics of photoplethysmographic (PPG) waveform to quantify stress and depression level posed by COVID-19 in first-line healthcare workers is explored. Results show that higher stress and depression level are moderately correlated with large systolic amplitude and parameters that might indicate early wave reflection. These results suggest that an arterial stiffness, quantified with PPG morphological characteristics, could provide valuable information in assessing mental healt

Triplet and reversed triplet mechanism CIDEP studied by quenching experiments

Quenching experiments are shown to provide a convenient tool to check for the presence of triplet mechanism (TM) spin polarisation in time-resolved EPR spectra following laser flash photolysis. The effect of the triplet quenchers, trans-1,3-pentadiene, fumaronitrile, azo-tert-butane and azo-n-butane upon the spectra following laser photolysis of acetone/propan-2-ol and benzophenone/propan-2-ol photosystems show that no TM polarisation is present in the former system but emissive TM is present in the latter. Use of 2,2′-azo-bis[isobutryronitrile] produces an anomalous emissive polarisation upon quenching, which is tentatively attributed to a reversed TM in the triplet sensitised azo-compoun

Substituent Effect on the Photoreduction Kinetics of Benzophenone

The kinetics of the photoreduction of four benzophenone derivatives by isopropyl alcohol was examined in acetonitrile, namely tetra-meta-trifluoromethyl-, di-para-trifluoromethyl-, di-para-methoxy benzophenone and for comparison the unsubstituted molecule itself. The basic spectroscopic (absorption and phosphorescence spectra) and photophysical (quantum yields, excited state energies) properties were established, and the key kinetic parameters were determined by the laser flash photolysis transient absorption technique. The rate coefficients of both the primary and secondary photoreduction reaction show remarkable dependence on ring substitution. This substantial effect is caused by the considerable change in the activation energy of the corresponding process. The experimental results as well as DFT quantum chemical calculations clearly indicate that these benzophenone derivatives all react as n-p* excited ketones, and the rate as well as the activation energy of the reduction steps change parallel with the reaction enthalpies, the determining factor being the stability of the forming aromatic ketyl radicals. The secondary photoreduction of benzophenones by the aliphatic ketyl radical formed in the primary step occurs via a hydrogen bonded complex. The binding energy of the hydrogen bonded complex between the aliphatic ketyl radical reactant and a solvent molecule is a critical parameter influencing the observable rate of the secondary photoreduction

Design and Synthesis of Pyrimidine Fused Heterocycles as Single Agents with Combination Chemotherapy Potential

This dissertation describes the design, synthesis and biological evaluation of pyrimidine fused heterocycles as single agents with combination chemotherapy potential. Major limitations of cancer chemotherapy include dose limiting toxicities of clinically used agents and the development of multidrug resistance by the tumor. Agents that interfere with microtubules are important antitumor agents. Tumor angiogenic mechanisms that are vital for tumor growth and metastasis are targeted by antiangiogenic agents. Antiangiogenic agents are usually not tumoricidal but are mainly cytostatic. Combination chemotherapy with antiangiogenic and cytotoxic agents have shown significant promise and several studies with such combinations are in progress in the clinic. Single agents with both antiangiogenic activities as well as cytotoxicity would afford single agents that circumvent pharmacokinetic problems of multiple agents, avoid drug–drug interactions, could be used at lower doses to alleviate toxicity, be devoid of overlapping toxicities, and delay or prevent tumor cell resistance. The work in this dissertation is centered on the design and synthesis of single entities that have both antiangiogenic effects and cytotoxic effects. These efforts led to the identification of structural features that are necessary for inhibition of tubulin polymerization. Structural modifications also led to the identification of novel antiangiogenic agents which inhibit one or more of the receptor tyrosine kinases (RTKs)– vascular endothelial growth factor receptor–2 (VEGFR2), platelet derived growth factor receptor–β (PDGFRβ) and epidermal growth factor receptor (EGFR). The complexity of the angiogenic pathways in tumors implies that disrupting a single mechanism of angiogenesis may not result in significant clinical success. Multiple RTKs are co–activated in tumors and redundant inputs drive and maintain downstream signaling, thereby limiting the efficacy of therapies targeting single RTKs. This work reviews the role of RTKs in angiogenesis, microtubules as antitumor targets, the vascular normalization theory and multitargeted agents. This work also reviews the synthesis of substituted pyrrolo[3,2–d]pyrimidines, furo[3,2–d]pyrimidines, pyrimido[5,4–b]indoles and b]. A discussion of methods employed in the synthesis of pyrimidine fused heterocycles as single agents with combination chemotherapy potential is provided

Benchmark calculations for reduced density-matrix functional theory

Reduced density-matrix functional theory (RDMFT) is a promising alternative approach to the problem of electron correlation. Like standard density functional theory, it contains an unknown exchange-correlation functional, for which several approximations have been proposed in the last years. In this article, we benchmark some of these functionals in an extended set of molecules with respect to total and atomization energies. Our results show that the most recent RDMFT functionals give very satisfactory results compared to more involved quantum chemistry and density functional approaches.Comment: 17 pages, 1 figur

Organic Chemistry I Drill (CHEM2210D) - Module 7 - Mechanisms and Substitutions

This module deals with chemical reactivity and mechanisms, and substitution reaction

I. Catalysis of Intra- and Intermolecular Schmidt Reactions. II. Copper-Catalyzed Oxaziridine-Mediated C-H Bond Oxidation. III. Synthesis and Cytotoxic Evaluation of Withalongolide A Analogues.

The research presented herein describes four separate projects, focusing on synthetic methodology development, discovery of novel cytotoxic agents, and natural product isolation. Catalysis of Intra- and Intermolecular Schmidt Reactions A method for carrying out the intramolecular Schmidt reaction of alkyl azides and ketones using a substoichiometric amount of catalyst is described. Following extensive screening, the use of the strong hydrogen-bond-donating solvent hexafluoro-2-propanol (HFIP) was found to be consistent with low catalyst loadings, which ranged from 2.5 mol % for favorable substrates to 25 mol % for more difficult cases. Reaction optimization, broad substrate scope, and preliminary mechanistic studies of this improved version of the reaction are discussed. The use of HFIP as the solvent also allowed for the extension of this methodology to intermolecular variants of Schmidt reaction favoring the development of mild, operationally simple, and more efficient protocols, requiring considerably less amounts of acid catalysts for these variants. Copper-Catalyzed Oxaziridine-Mediated C-(&ndash)H Bond Oxidation. The highly regioand chemoselective oxidation of an activated C−(&ndash)H bond via a copper-catalyzed reaction of oxaziridine is described. The oxidation proceeded with a variety of substrates, primarily comprising of allylic and benzylic examples, as well as one example of an otherwise unactivated tertiary C−(&ndash)H bond. The mechanism of the reaction is proposed to involve single-electron transfer (SET) to the oxaziridines to generate a copper-bound radical anion, followed by hydrogen atom abstraction and collapse to products, with regeneration of the catalyst by a final SET event. The involvement of allylic radical intermediates en route to the product was supported by a radical-trapping experiment with TEMPO. Synthesis and Cytotoxic Evaluation of Withalongolide A Analogues. The natural product withaferin A exhibits potent antitumor activity and other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was reported to possess cytotoxic activity against head and neck squamous cell carcinoma (HNSCC). Interestingly, semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure-(&ndash)activity relationship (SAR), 20 new semisynthetic analogues of this highly oxygenated withalongolide A were designed, synthesized, and evaluated for cytotoxic activity against four different cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A. Isolation of Withalongolide O from Physalis longifolia. The SAR analysis of reported bioactive withanolides revealed certain crucial structural requisites for possessing a potent cytotoxic activity. The semisynthesis of a putative unnatural withanolide incorporating all the basic and essential structural features to boost the antiproliferative activity was contemplated. Withaferin A was considered as an appropriate starting material for this purpose. Although the semisynthetic efforts met with failure, it was during the isolation of withaferin A from the crude plant extract that we discovered a novel withanolide, withalongolide O. The structure of withalongolide O was determined using various spectroscopic techniques and subsequently confirmed by X-ray crystallographic analysis. Both withalongolide O and its diacetate exhibited potent cytotoxicity against four different cancer cell lines

The kinetics and solvent effects on the thermal decomposition of isopropyl peroxide and 1, 2-dioxane

Rates of H2 formation have been determined for the thermal decomposition of isopropyl peroxide at l30o-l50oC in toluene and methanol and at l400C in isopropyl alcohol and water. Product studies have been carried out at l400C in these solvents. The decomposition of isopropyl peroxide was shown to be unimolecular with energies of activation in toluene, and methanol of 39.1, 23.08 Kcal/mole respectively. It has been shown that the rates of H2 formation in decomposition of isopropyl peroxide are solvent dependent and that the ~ vs "'2';' values (parameters for solvent polarity) givesastraight line. Mechanisms for hydrogen production are discussed which satisfactorily explain the stabilization of the six-centered transition state by the solvent. One possibility is that of conformation stabilization by solvent and the other, a transition state with sufficient ionic character to be stabilized by a polar solvent. Rates of thermal decomposition of 1,2-dioxane in tert-butylbenzene at l40o-l70oC have been determined. The activation energy was found to be 33.4 Kcal/mole. This lower activation energy, compared to that for the decomposition of isopropyl peroxide in toluene (39.1 Kcal/mole) has been explained in terms of ring strain. Decomposition of 1,2 dioxane in MeOH does not follow a first order reaction. Several mechanisms have been suggested for the products observed for decomposition of 1;2-dioxane in toluene and methanol