Babur Z. Chowdhry

Bio: Babur Z. Chowdhry is an academic researcher from University of Greenwich. The author has contributed to research in topics: Raman spectroscopy & Differential scanning calorimetry. The author has an hindex of 39, co-authored 192 publications receiving 6000 citations.

Interaction of Delta- and Lambda-[Ru(phen)2DPPZ]2+ with DNA: A Calorimetric and Equilibrium Binding Study

Abstract: Fluorescence and absorption spectroscopy, isothermal titration calorimetry, and viscosity measurements have been used to characterize the interaction of Delta and Lambda [Ru(phen)(2)DPPZ](2+) with calf thymus DNA. The method of continuous variations revealed two distinct binding stoichiometries for both Delta- and Lambda-DPPZ, corresponding to 0.7 and 3 mol of base pair/mol of ligand. Binding isotherms were obtained for the two enantiomers, both of which show strong binding to DNA, with K = 3.2 x 10(6) M(-1) bp and 1.7 x 10(6) M(-1) bp for the Delta and Lambda isomers, respectively, at 25 degrees C in solutions containing 50 mM NaCl. Titration calorimetry gave Delta H values of +0.3 kcal mol(-1) for Delta-DPPZ and +2.9 kcal mol(-1) for Lambda-DPPZ for their interaction with DNA. These small positive enthalpies, which were confirmed using thermal difference spectroscopy, indicated that the binding of these compounds to DNA is entropically driven. An enthalpy of +2.5 kcal mol(-1) was obtained for the binding of the parent compound, tris(phenanthroline)-Ru(II), to DNA. Titration of all three compounds into buffer gave a nonnegligible heat of dilution. The salt dependence of the binding constant was examined for both isomers. The slope SK = (delta logK/delta log[Na+]) was found to be 1.9 and 2.1 for the Delta and Lambda isomers, respectively. By using polyelectrolyte theory to interpret the observed salt dependence of the equilibrium constant, it can be shown that there is a significant nonelectrostatic contribution to the binding constant. Relative viscosity experiments showed that both Delta- and Lambda-DPPZ increase the length of rod-like DNA, in a manner consistent with binding by classical intercalation. Fluorescence energy transfer experiments provided additional evidence for the intercalation of Delta- and Lambda-[Ru(phen)(2)DPPZ](2+) into DNA.

Ion mobility spectrometry-mass spectrometry (IMS-MS) of small molecules: Separating and assigning structures to ions.

Abstract: The phenomenon of ion mobility (IM), the movement/transport of charged particles under the influence of an electric field, was first observed in the early 20th Century and harnessed later in ion mobility spectrometry (IMS). There have been rapid advances in instrumental design, experimental methods, and theory together with contributions from computational chemistry and gas-phase ion chemistry, which have diversified the range of potential applications of contemporary IMS techniques. Whilst IMS-mass spectrometry (IMS-MS) has recently been recognized for having significant research/applied industrial potential and encompasses multi-/cross-disciplinary areas of science, the applications and impact from decades of research are only now beginning to be utilized for “small molecule” species. This review focuses on the application of IMS-MS to “small molecule” species typically used in drug discovery (100-500 Da) including an assessment of the limitations and possibilities of the technique. Potential future developments in instrumental design, experimental methods, and applications are addressed. The typical application of IMS-MS in relation to small molecules has been to separate species in fairly uniform molecular classes such as mixture analysis, including metabolites. Separation of similar species has historically been challenging using IMS as the resolving power, R, has been low (3-100) and the differences in collision cross-sections that could be measured have been relatively small, so instrument and method development has often focused on increasing resolving power. However, IMS-MS has a range of other potential applications that are examined in this review where it displays unique advantages, including: determination of small molecule structure from drift time, “small molecule” separation in achiral and chiral mixtures, improvement in selectivity, identification of carbohydrate isomers, metabonomics, and for understanding the size and shape of small molecules. This review provides a broad but selective overview of current literature, concentrating on IMS-MS, not solely IMS, and small molecule applications (review).

Colloidal copolymer microgels of N-isopropylacrylamide and acrylic acid: pH, ionic strength and temperature effects

Abstract: Aqueous colloidal microgels have been prepared, based on poly(N-isopropylacrylamide)[poly(NIPAM)], cross-linked with bisacrylamide, containing 5% w/w acrylic acid (AAc) as a comonomer. Transmission electron micrographs of the microgels show that the copolymer microgels are monodisperse spheres. The size of the microgel particles containing 5% AAc has been studied, using dynamic light scattering, as a function of pH (3–10), ionic strength (10–4–10–1M NaCl) and temperature (20–75 °C). The hydrodynamic diameter of the copolymer microgels decrease both with increasing ionic strength (at pH 6 and 25 °C) and reversibly with increasing temperature at pH values of 2.6, 3.4 and 6.5. However, under isothermal conditions in 10–3M NaCl at 25 °C, the hydrodynamic diameter increases in going from pH 3.3–9.4. In addition, the temperature-induced conformational changes in the polymer chains have been followed using high-sensitivity differential scanning calorimetry (HSDSC). A comparison is made with the behaviour of poly(NIPAM) microgel particles, not containing AAc. Explanations are offered to account for the pronounced difference in the physico-chemical properties observed.

Palladium-Catalyzed Ligand-Directed C−H Functionalization Reactions

Abstract: 1.1 Introduction to Pd-catalyzed directed C–H functionalization The development of methods for the direct conversion of carbon–hydrogen bonds into carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon bonds remains a critical challenge in organic chemistry. Mild and selective transformations of this type will undoubtedly find widespread application across the chemical field, including in the synthesis of pharmaceuticals, natural products, agrochemicals, polymers, and feedstock commodity chemicals. Traditional approaches for the formation of such functional groups rely on pre-functionalized starting materials for both reactivity and selectivity. However, the requirement for installing a functional group prior to the desired C–O, C–X, C–N, C–S, or C–C bond adds costly chemical steps to the overall construction of a molecule. As such, circumventing this issue will not only improve atom economy but also increase the overall efficiency of multi-step synthetic sequences. Direct C–H bond functionalization reactions are limited by two fundamental challenges: (i) the inert nature of most carbon-hydrogen bonds and (ii) the requirement to control site selectivity in molecules that contain diverse C–H groups. A multitude of studies have addressed the first challenge by demonstrating that transition metals can react with C–H bonds to produce C–M bonds in a process known as “C–H activation”.1 The resulting C–M bonds are far more reactive than their C–H counterparts, and in many cases they can be converted to new functional groups under mild conditions. The second major challenge is achieving selective functionalization of a single C–H bond within a complex molecule. While several different strategies have been employed to address this issue, the most common (and the subject of the current review) involves the use of substrates that contain coordinating ligands. These ligands (often termed “directing groups”) bind to the metal center and selectively deliver the catalyst to a proximal C–H bond. Many different transition metals, including Ru, Rh, Pt, and Pd, undergo stoichiometric ligand-directed C–H activation reactions (also known as cyclometalation).2,3 Furthermore, over the past 15 years, a variety of catalytic carbon-carbon bond-forming processes have been developed that involve cyclometalation as a key step.1b–d,4 The current review will focus specifically on ligand-directed C–H functionalization reactions catalyzed by palladium. Palladium complexes are particularly attractive catalysts for such transformations for several reasons. First, ligand-directed C–H functionalization at Pd centers can be used to install many different types of bonds, including carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon linkages. Few other catalysts allow such diverse bond constructions,5,6,7 and this versatility is predominantly the result of two key features: (i) the compatibility of many PdII catalysts with oxidants and (ii) the ability to selectively functionalize cyclopalladated intermediates. Second, palladium participates in cyclometalation with a wide variety of directing groups, and, unlike many other transition metals, promotes C–H activation at both sp2 and sp3 C–H sites. Finally, the vast majority of Pd-catalyzed directed C–H functionalization reactions can be performed in the presence of ambient air and moisture, making them exceptionally practical for applications in organic synthesis. While several accounts have described recent advances, this is the first comprehensive review encompassing the large body of work in this field over the past 5 years (2004–2009). Both synthetic applications and mechanistic aspects of these transformations are discussed where appropriate, and the review is organized on the basis of the type of bond being formed.

Handbook of Chemistry and Physics

Abstract: There is a special reason for reviewing this book at this time: it is the 50th edition of a compendium that is known and used frequently in most chemical and physical laboratories in many parts of the world. Surely, a publication that has been published for 56 years, withstanding the vagaries of science in this century, must have had something to offer. There is another reason: while the book is a standard fixture in most chemical and physical laboratories, including those in medical centers, it is not as frequently seen in the laboratories of physician's offices (those either in solo or group practice). I believe that the Handbook can be useful in those laboratories. One of the reasons, among others, is that the various basic items of information it offers may be helpful in new tests, either physical or chemical, which are continuously being published. The basic information may relate

Designing hydrogels for controlled drug delivery.

Abstract: Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.

Recognition and reaction of metallointercalators with DNA.

Abstract: The design of small complexes that bind and react at specific sequences of DNA becomes important as we begin to delineate, on a molecular level, how genetic information is expressed. A more complete understanding of how to target DNA sites with specificity will lead not only to novel chemotherapeutics but also to a greatly expanded ability for chemists to probe DNA and to develop highly sensitive diagnostic agents.