Amphiphilic block copolymer self‐assemblies of poly(NVP)‐b‐poly(MDO‐co‐vinyl esters): Tunable dimensions and functionalities

Functional, degradable polymers were synthesized via the copolymerization of vinyl acetate (VAc) and 2‐methylene‐1,3‐dioxepane (MDO) using a macro‐xanthate CTA, poly(N‐vinylpyrrolidone), resulting in the formation of amphiphilic block copolymers of poly(NVP)‐b‐poly(MDO‐co‐VAc). The behavior of the block copolymers in water was investigated and resulted in the formation of self‐assembled nanoparticles containing a hydrophobic core and a hydrophilic corona. The size of the resultant nanoparticles was able to be tuned with variation of the hydrophilic and hydrophobic segments of the core and corona by changing the incorporation of the macro‐CTA as well as the monomer composition in the copolymers, as observed by Dynamic Light Scattering, Static Light Scattering, and Transmission Electron Microscopy analyses. The concept was further applied to a VAc derivative monomer, vinyl bromobutanoate, to incorporate further functionalities such as fluorescent dithiomaleimide groups throughout the polymer backbone using azidation and “click” chemistry as postpolymerization tools to create fluorescently labeled nanoparticles. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2699–2710     

Rearrangement of 3-membered 1,1,2-trifluorobromonium and iodonium ions and comparison of trifluorochloronium to fluorocarbenium ions

Reactions of chlorine (Cl(2)) with 4-halo-1,1,2-trifluorobut-1-enes (1, 2, or 3) give open-ion intermediates A and E that are in equilibrium. The open-chloronium ions (E) rearrange to a five-membered-ring halonium ion during ionic chlorination of 3 when the number-4 halo-substituent is iodine. Three-membered-ring bromonium and iodonium ions from alkenes 1, 2, or 3 are rather symmetrical and similar in structure. Quantum chemical calculations show that five-membered-ring halonium ion intermediates are 11 to 27 kcal/mol more stable than the three-membered-ring halonium ions or the open-ions A and E. The five-membered-ring intermediates lead to rearranged products. Rearranged products increase as the number-4 halogen (Z) becomes more nucleophilic (Z: Cl < Br < I). Open chloronium ions from ionic chlorination of terminal fluorovinyl alkenes are compared to the open ions generated by protons to similar alkenes.     

Vibrational spectra of anhydrous and monohydrated caffeine and theophylline molecules and crystals

Density functional theory and classical molecular dynamics simulations are used to investigate the vibrational spectra of caffeine and theophylline anhydrous and monohydrate molecules and those of their crystalline anhydrous and monohydrated states, with emphasis in the terahertz region of the spectra. To better understand the influence of water in the monohydrate crystal spectra, we analyze the vibrational spectra of water monomer, dimer, tetramer, and pentamer, and also those of liquid water at two different temperatures. In small water clusters, we observe the progressive addition of translational and librational modes to the terahertz region of the spectra. The water spectra predicted by rigid and flexible water models is examined with classical molecular dynamics, and the respective peaks, especially in the terahertz region, are compared with those found in the small clusters. Similar analysis done for caffeine and theophylline monohydrate molecules using density functional theory clearly shows the presence of water modes in the librational states and in the water stretching region. Molecular dynamics of caffeine and theophylline anhydrous and monohydrate crystals reveal the influence of vibrations from the molecule-molecule (caffeine or theophylline) crystal stacks and those from the water-molecule interactions found in the monohydrate molecules and new modes from molecule-molecule, water-molecule, and water-water hydrogen bonding interactions arising from collective effects in the crystal structure. Findings illustrate challenges of terahertz technology for the detection of specific substances in condensed phases.     

In search of efficient 5-endo-dig cyclization of a carbon-centered radical: 40 years from a prediction to another success for the Baldwin rules

Despite being predicted to be stereoelectronically favorable by the Baldwin rules, efficient formation of a C-C bond through a 5-endo-dig radical cyclization remained unknown for more than 40 years. This work reports a remarkable increase in the efficiency of this process upon beta-Ts substitution, which led to the development of an expedient approach to densely functionalized cyclic 1,3-dienes. Good qualitative agreement between the increased efficiency and stereoselectivity for the 5-endo-dig cyclization of Ts-substituted vinyl radicals and the results of density functional theory analysis further confirms the utility of computational methods in the design of new radical processes. Although reactions of Br atoms generated through photochemical Ts-Br bond homolysis lead to the formation of cyclic dibromide side products, the yields of target bromosulfones in the photochemically induced reactions can be increased by recycling the dibromide byproduct into the target bromosulfones through a sequence of addition/elimination reactions at the exocyclic double bond. Discovery of a relatively efficient radical 5-endo-dig closure, accompanied by a C-C bond formation, provides further support to stereoelectronic considerations at the heart of the Baldwin rules and fills one of the last remaining gaps in the arsenal of radical cyclizations.     

Electrochemical and spectroscopic characterization of a series of mixed-ligand diruthenium compounds

The electrochemistry and spectroelectrochemistry of a novel series of mixed-ligand diruthenium compounds were examined. The investigated compounds having the formula Ru(2)(CH(3)CO(2))(x)(Fap)(4-x)Cl where x = 1-3 and Fap is 2-(2-fluoroanilino)pyridinate anion were made from the reaction of Ru(2)(CH(3)CO(2))(4)Cl with 2-(2-fluoroanilino)pyridine (HFap) in refluxing methanol. The previously characterized Ru(2)(Fap)(4)Cl as well as the three newly isolated compounds represented as Ru(2)(CH(3)CO(2))(Fap)(3)Cl (1), Ru(2)(CH(3)CO(2))(2)(Fap)(2)Cl (2), and Ru(2)(CH(3)CO(2))(3)(Fap)Cl (3) possess three unpaired electrons with a Ru(2)(5+) dimetal core. Complexes 1 and 2 have well-defined Ru(2)(5+/4+) and Ru(2)(5+/6+) redox couples in CH(2)Cl(2), but 3 exhibits a more complicated electrochemical behavior due to equilibria involving association or dissociation of the anionic chloride axial ligand on the initial and oxidized or reduced forms of the compound. The E(1/2) values for the Ru(2)(5+/4+) and Ru(2)(5+/6+) processes vary linearly with the number of CH(3)CO(2)(-) bridging ligands on Ru(2)(CH(3)CO(2))(x)(Fap)(4-x)Cl and plots of reversible half-wave potentials vs the number of acetate groups follow linear free energy relationships with the largest substituent effect being observed for the oxidation. The major UV-visible band of the examined compounds in their neutral Ru(2)(5+) form is located between 550 and 800 nm in CH(2)Cl(2) and also varies linearly with the number of CH(3)CO(2)(-) ligands on Ru(2)(CH(3)CO(2))(x)(Fap)(4-x)Cl. The electronic spectra of the singly oxidized and singly reduced forms of each diruthenium species were characterized by UV-visible spectroelectrochemistry in CH(2)Cl(2).     

Studies of finite molecular chains: synthesis, structural, magnetic and inelastic neutron scattering studies of hexa- and heptanuclear chromium horseshoes

We report the synthesis and structural characterisation of a family of finite molecular chains, specifically [{[R(2)NH(2)](3)[Cr(6)F(11)(O(2)CCMe(3))(10)]}(2)] (in which R=nPr 1, Et 2, nBu 3), [{Et(2)NH}(2){[Et(2)NH(2)](3)[Cr(7)F(12)(O(2)CCMe(3))(12)][HO(2)CCMe(3)](2)}(2)] (4), [{[Me(2)NH(2)](3)[Cr(6)F(11)(O(2)CCMe(3))(10)]2.5 H(2)O}(4)] (5) and [{[iPr(2)NH(2)](3)[Cr(7)F(12)(O(2)CCMe(3))(12)]}(2)] (6). The structures all contain horseshoes of chromium centres, with each Cr...Cr contact within the horseshoe bridged by a fluoride and two pivalates. The horseshoes are linked through hydrogen bonds to the secondary ammonium cations in the structure, leading to di- and tetra-horseshoe structures. Through magnetic measurements and inelastic neutron scattering studies we have determined the exchange coupling constants in 1 and 6. In 1 it is possible to distinguish two exchange interactions, J(A)=-1.1 meV and J(B)=-1.4 meV; J(A) is the exchange interactions at the tips of the horseshoe and J(B) is the exchange within the body of the horseshoe (1 meV=8.066 cm(-1)). For 6 only one interaction was needed to model the data: J=-1.18 meV. The single-ion anisotropy parameters for Cr(III) were also derived for the two compounds as: for 1, D(Cr)=-0.028 meV and |E(Cr)|=0.005 meV; for 6, D(Cr)=-0.031 meV. Magnetic-field-dependent inelastic neutron scattering experiments on 1 allowed the Zeeman splitting of the first two excited states and level crossings to be observed. For the tetramer of horseshoes (5), quantum Monte Carlo calculations were used to fit the magnetic susceptibility behaviour, giving two exchange interactions within the horseshoe (-1.32 and -1.65 meV) and a weak inter-horseshoe coupling of +0.12 meV. Multi-frequency variable-temperature EPR studies on 1, 2 and 6 have also been performed, allowing further characterisation of the spin Hamiltonian parameters of these chains.     

A Buchwald–Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3-Ligase PROTACs**

A palladium-catalysed Buchwald–Hartwig amination for lenalidomide-derived aryl bromides was optimised using high throughput experimentation (HTE). The substrate scope of the optimised conditions was evaluated for a range of alkyl- and aryl- amines and functionalised aryl bromides. The methodology allows access to new cereblon-based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields.     

Methodology for the synthesis of the core EFGH rings of diazonamide A

Conversion of substituted 2-oxindoles into 2-thionoindoles followed by Raney nickel desulfurization provides a mild method for synthesizing the core EFGH rings of diazonamide A.     

Interaction of the glycoalkaloid tomatine with DMPC and sterol monolayers studied by surface pressure measurements and Brewster angle microscopy

The interaction of the glycoalkaloid tomatine with monolayers of dimyristoylphosphatidylcholine (DMPC) and cholesterol, as well as other selected sterols, has been investigated using surface pressure measurements at constant area and Brewster angle microscopy (BAM). The interaction of tomatine with sterol monolayers is found to vary with the structure of the sterol. The interaction of tomatine with cholesterol-containing monolayers results in a surface pressure increase accompanied by the appearance of a mottled texture. Morphological changes are observed that suggest the formation of tomatine-cholesterol complexes that aggregate at the water-air interface. No morphology change observable by BAM is observed for monolayers containing epicholesterol, suggesting that the stereochemistry of hydrogen bonding between the sterol and the sugar units on tomatine is of particular significance. Strong interactions are observed with cholestanol- and coprostanol-containing monolayers, and BAM reveals formation of spiked aggregates upon interaction with 7:3 mole ratio DMPC/coprostanol mixed monolayers. More modest surface pressure changes are observed for cholestenone- and epicoprostanol-containing monolayers. A much smaller surface pressure increase is observed when tomatine is injected beneath a pure DMPC monolayer.