A novel polymer-modified thermosensitive liposome (pTSL) was developed for the delivery of Doxorubicin (DOX) for cancer therapy. Copolymers containing temperature-responsive Nisopropylacrylamide (NIPAAm) and pH-responsive propylacrylic acid (PAA) were synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization, yielding copolymers with dual pH/temperature dependent phase transition properties. When attached to liposomes, these copolymers were membrane-disruptive in a pH/temperature dependent manner. pTSL demonstrated enhanced release profile and significantly lower thermal dose threshold when compared to traditional thermosensitive formulations, and were stable in serum with minimal drug leakage over time. These liposomes thus have the potential to dramatically reduce the risk of damage to healthy tissues that is normally associated with liposomal cancer therapy.

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Comparison of pairs of physiochemical properties of phosphines and their complexes demonstrates that, in general, at least four independent stereoelectronic parameters are in general required to describe the variations in these properties. Consequently, any two-parameter model such as Drago's E/C model will have limited use in correlation analyses involving phosphines. The QALE analysis of E B and C B shows that these parameters are linear combinations of the QALE parameters χ and θ, with a small contribution from E ar. Thus, successful application of the E/C model will be restricted to the situation where the property being analyzed depends primarily on χ and θ.

The [Rh(cod)Cl]2/(R)-BINAP catalyzed hydrosilylation reaction between acetophenone and H2SiPh2, H2SiEt2, H2SiBu2, HSiBu3, HSiPh3, and HSi(p-F3CC6H4)3 in benzene-d 6 at 63 °C has been studied by 1H NMR spectroscopy, GC/MS, and H/D exchange experiments with acetophenone-d 6. The reactions afford varying amounts of PhCH(OSiZ3)Me (3), PhC(OSiZ3)CH2 (4), and PhCH(OH)Me (5). The product distribution of the reaction is dependent on the order of mixing for the secondary silanes but independent of the order of mixing for tertiary silanes. The product distributions and initial rates of reaction of the tertiary silanes, which react more slowly than the secondary silanes, are dependent on the stereoelectronic properties of the silane, with HSi(p-F3CC6H4)3 being 10 times more reactive than HSiPh3. The reaction involving HSiBu3 is first order in the initial concentration of [Rh(cod)Cl]2/(R)-BINAP as well as the concentration of HSiBu3 but shows a saturation effect at high concentrations of acetophenone. In the earliest phases of the reaction, the coordinated cyclooctadiene is liberated and converted to cyclooctane and cyclooctene. The requisite hydrogens for the hydrogenation process come mainly from HSiBu3. The products 4 and 5 appear to be formed independently of the formation of 3. The catalysts for the formation of 4 and 5 appeared to decay, thereby abruptly terminating the formation of these materials after about 40% of the acetophenone had been consumed. Simulation of the kinetic results, based on the Ojima mechanism, qualitatively fits the production of 3.

Isoequilibrium behavior arising from the temperature dependence of ΔG° of families of complexes containing phosphorus(III) ligands provides a diagnostic method for evaluating a model (used to describe ligand effects) and the associated set of stereoelectronic parameters. This evaluation is based not on the quality of a linear free energy relationship, but rather on the results of a thermodynamic argument. Studies of the temperature dependence of E°/T values for the η-Cp(CO)(L)Fe(COMe)+/η-Cp(CO)(L)Fe(COMe)0 couple, where L is a phosphorus(III) ligand, provide isoequilibrium data to test the ECW model for analysis of ligand effects. The ECW model fails this test. Therefore, we conclude that the ECW model is, in general, inadequate to describe the stereoelectronic properties of phosphorus(III) ligands.

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Analysis of the E°values of the η-Cp(CO)(L)Fe(COMe) +/o couple (measured via cyclic voltammetry at 229, 252, 264, 273, and 293 K in acetonitrile/0.1 M TBAH) has revealed different isoequilibrium behavior for P(p-XC 6 H 4 ) 3 and PR 3 . We classify ligands as a family when they exhibit a single isoequilibrium point. A family of ligands affects a property via variation of a single, or effectively single, parameter. Thus, through isoequilibrium behavior, we have an unambiguous way to identify families, which in quantitative analysis of ligand effects (QALE), must be treated separately in the preliminary graphical analysis of data that leads to the full regression analysis. The QALE model predicts that there is an isoequilibrium temperature associated with each stereoelectronic parameter; i.e., for each parameter, there is a specific temperature where the effect disappears. The fan-shaped arrays of lines that result when E°/T is plotted versus either 1/T or the stereoelectronic parameter gives insight into the nature of and the number of stereoelectronic parameters necessary to describe the system and the partitioning of steric effects between enthalpy and entropy. In this particular system, steric effects are almost entirely an entropic phenomenon.

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