Hermanus C.M. Vosloo

Development of microporous drug-releasing films cast from artificial nanosized latexes of poly(styrene-co-methyl methacrylate) or poly(styrene-co-ethyl methacrylate)

Two sets of copolymers comprising of styrene and either methyl or ethyl methacrylate as comonomer were conveniently synthesized by microemulsion copolymerization. The purified materials were characterized by GPC-MALLS and were shown to form artificial nanolatexes in THF. ATR-FTIR analysis revealed differences in copolymer composition and based on the copolymer properties, a selection of copolymers was chosen to cast drug-loaded, microporous films that exhibit microencapsulation of drug agglomerates. The contact angles of the copolymers suggested potential applications in medical devices to prevent the formation of bacterial biofilms that commonly result in infections. Additionally, the different copolymeric films showed two phases of drug release characterized by a rapid initial drug release followed by a zero-order phase. Depending on the application, one could select the copolymer films that best suited the application i.e. for short-term drug release applications such as urinary catheters or long-term applications such as artificial implants.

DFT investigation of the 1-octene metathesis reaction mechanism with the Phobcat precatalyst

AbstractThe productive self-metathesis reaction of 1-octene in the presence of the Phobcat precatalyst [RuCl2(Phoban-Cy)2(=CHPh)] using density functional theory was investigated and compared to the Grubbs 1 precatalyst [RuCl2(PCy3)2(=CHPh)]. At the GGA-PW91/DNP level, the geometry optimization of all the participating species and the PES scans of the various activation and catalytic cycles in the dissociative mechanism were performed. The formation of the catalytically active heptylidene species is kinetically and thermodynamically favored, while the formation of trans-tetradecene is thermodynamically favored. FigurePhobcat active species in 1-octene metathesis

Towards a better understanding of alkene metathesis: elucidating the properties of the major metal carbene catalyst types

The difference in activity of metal carbene catalysts has a major influence on the efficiency and application of these metal carbenes as metathesis catalysts. The focus of this research is to examine the properties of the major metal carbene catalyst types to understand the general activity trend. A comparative investigation of the foremost Fischer-, Tebbe-, Grubbs-, and Schrock-type metal carbenes was done using a qualitative structure–activity type computational method via principal component analysis. The effect of the change in metal atom as well as the change in ligands was specifically considered. Four Fischer-, a Tebbe-, five Grubbs-, and a Schrock-type carbene were investigated in this regard. Geometry optimizations of all species were done at the GGA/PBE/DNP level with Materials Studio DMol3 and subsequent single-point energy calculations were done with Gaussian at the PBEPBE level with the cc-pVQZ-type basis sets. Results showed that the descriptors extracted by the principal component analyses could successfully reproduce or match the generalized trend for metathesis activity, highlighting the importance of the frontier orbitals in the metathesis reaction.Graphical Abstract

A DFT computational study of phosphine ligand dissociation versus hemilability in a Grubbs-type precatalyst containing a bidentate ligand during alkene metathesis

Using density functional theory, the metathesis reaction of 1-octene in the presence of a Grubbs-type ruthenium alkylidene complex bearing a chelating pyridinyl alcoholate ligand, [RuCl(L)(O∧ N)( = CHPh)] (L = H2IMes or PCy3, O∧ N = 1-(2′-pyridinyl)cyclohexan-1-olate)), was investigated. The complete geometry optimisation and activation energy of various activation steps in the dissociative mechanism were performed at the GGA-PW91/DNP level of theory using Accelrys Materials Studio® 4.0. Two possible precatalyst initiations were explored, i.e. the dissociation of the labile N-atom of the O∧ N-ligand as well as the dissociation of ligand L, due to the belief that ruthenium-catalysed metathesis reactions proceed through 14-electron intermediates. The formation of the catalytically active heptylidene species is kinetically favoured for both the first- and second-generation chelating complexes. The computational results are in agreement with the experimental results obtained with NMR for the second-generation system. The computational results suggest that both phosphine ligand dissociation and hemilability may play a role in the metathesis reaction with the first-generation system.

Improved Metathesis Lifetime: Chelating Pyridinyl-Alcoholato Ligands in the Second Generation Grubbs Precatalyst

Hemilabile ligands can release a free coordination site “on demand” of an incoming nucleophilic substrate while occupying it otherwise. This is believed to increase the thermal stability and activity of catalytic systems and therefore prevent decomposition via free coordination sites. In this investigation chelating pyridinyl-alcoholato ligands were identified as possible hemilabile ligands for incorporation into the second generation Grubbs precatalyst. The O,N-alcoholato ligands with different steric bulk could be successfully incorporated into the precatalysts. The incorporation of the sterically hindered, hemilabile O,N-ligands improved the thermal stability, activity, selectivity and lifetime of these complexes towards the metathesis of 1-octene. A decrease in the activity of the second generation Grubbs precatalyst was additionally observed after incorporating a hemilabile O,N-ligand with two phenyl groups into the system, while increasing their lifetime.

A Molecular modeling study of the changes of some steric properties of the precatalysts during the olefin metathesis reaction

The productive self‐metathesis of 1‐octene with a series of new phosphine ligated Grubbs‐type precatalysts was studied. The resulting structures were used to compare some steric properties of the new precatalysts with those of well‐known precatalysts. The possibility of α‐CC agnostic stabilization as well as the ability of the ligands to shield the metal was studied. A comparison of the obtained data, pointed to the unlikelihood that α‐CC agostic stabilization is a major contribution to the stabilization of the various metallacyclobutane rings. The similarity in the ability of the ligands to shield the metal also raised questions about the comparison of experimentally observed trends with those obtained theoretically.

A comparison of low and high activity precatalysts: do the calculated energy barriers during the self-metathesis reaction of 1-octene correlate with the precatalyst metathesis activity?

The self‐metathesis reaction of 1‐octene with several well‐known Grubbs‐type precatalysts and the new Z‐selective Grubbs precatalyst were studied with molecular modeling. The obtained Gibbs‐free energy values for all the steps during the productive metathesis of 1‐octene were compared to the values obtained for some low catalytic activity precatalysts. Determining how the Gibbs‐free energy values of highly active precatalysts compare to that of low catalytic activity precatalysts gave a deeper insight into the mechanism. The questionable correlation of the theoretically observed trends with those obtained experimentally does point to the need to be very cautious when making assumptions from theoretical results without a sufficiently large dataset.

Application of Size Exclusion Chromatography in the Development and Characterization of Nanoparticulate Drug Delivery Systems

Abstract The successful production of effective nanoparticulate drug delivery systems depends on maintaining the characteristics of the starting materials and the final formulation. Since compendial standards for traditional drug delivery systems do not always apply to nanosystems, analytical procedures for nanosized delivery systems must be established. This will ensure the quality of such products as they reach the marketplace. Size exclusion chromatography provides a method to continuously monitor all the development stages of nanoparticulate drug delivery systems, thereby, ensuring the quality of the starting materials used and the final product. The primary properties that can be monitored with this technique include particle size and molecular weight. Information about these properties not only serves as quality control measures, but can be used to monitor formulations for potential degradation products or impurities. Recent advances in size exclusion chromatography, such as the introduction of rapid analysis size exclusion columns and new chromatographs will make this technique even more applicable for nanosystem characterization. This implies that size exclusion chromatography might become an essential, economically feasible, and necessary analytical tool for ensuring the quality of nanoparticulate drug delivery systems.

Synthesis and Application of the Transition Metal Complexes of α-Pyridinyl Alcohols, α-Bipyridinyl Alcohols, α,α’-Pyridinyl Diols and α,α’-Bipyridinyl Diols in Homogeneous Catalysis

The paper presents a comprehensive survey on the synthetic procedures of transition metal complexes of α-pyridinyl alcoholato, α-bipyridinyl alcoholato, α,α’-pyridinyl dialcoholato and α,α’-bipyridinyl dialcoholato ligands and their coordination chemistry. Greater emphasis is, however, given to the catalytic activity of the complexes in homogeneous and asymmetric chemical reactions. The multidentate character of the pyridinyl alcohols and/or bipyridinyl diols is of great importance in the complexation with a large number and type of transition metals. The transition metal complexes of pyridinyl alcoholato or bipyridinyl dialcoholato ligands in most cases, and a few pyridinyl alcohols alone, were used as catalysts in homogeneous and chemical asymmetric reactions. In most of the homogeneously catalysed enantioselective chemical reactions, limited numbers and types of pyridinyl alcohols and or bipyridinyl diols were used in the preparation of chiral catalysts that led to a few investigations on the catalytic importance of the pyridinyl alcohols.

Experimental and reaction kinetic investigation of 1-octene metathesis reaction with Hoveyda-Grubbs first generation precatalyst

Abstract In this work, we report the catalytic performance of the first generation Hoveyda-Grubbs precatalyst for the metathesis reaction of 1-octene. The reaction temperature (30 to 100°C) and catalyst load (1-octene/Ru molar ratio 5,000 to 10,000) were varied and quantities such as product distribution, activity and selectivity were evaluated. Reaction temperature showed a significant effect and turn over numbers as high as 4458 were observed for this system. Two competing mechanisms were observed for temperatures above 60°C, namely metathesis and isomerisation. The experimental product-time distribution data for the complex parallel reaction system was fairly accurately described by three elementary pseudo-first order reaction rates. The effects of temperature (Arrhenius Equation) and catalyst load were incorporated in the observed rate constant. The observed activation energies were around 10 kcal/mol.