Reactivity of alkyl versus silyl peroxides. The consequences of 1, 2-silicon bridging on the epoxidation of alkenes with silyl hydroperoxides and bis(trialkylsilyl)peroxides

The bond dissociation energies for a series of silyl peroxides have been calculated at the G2 and CBS-Q levels of theory. A comparison is made with the O-O BDE of the corresponding dialkyl peroxides, and the effect of the O-O bond strength on the activation barrier for oxygen atom transfer is discussed. The O-O bond dissociation enthalpies (DeltaH(298)) for bis (trimethylsilyl) peroxide (1) and trimethylsilyl hydroperoxide (2) are 54.8 and 53.1 kcal/mol, respectively at the G2 (MP2) and CBS-Q levels of theory. The O-O bond dissociation energies computed at G2 and G2(MP2) levels for bis(tert-butyl) peroxide and tert-butyl hydroperoxide are 45.2 and 48.3 kcal/mol, respectively. The barrier height for 1,2-methyl migration from silicon to oxygen in trimethylsilyl hydroperoxide is 47.9 kcal/mol (MP4//MP2/6-31G). The activation energy for the oxidation of trimethylamine to its N-oxide by bis(trimethylsilyl) peroxide is 28.2 kcal/mol (B3LYP/6-311+G(3df,2p)// B3LYP/6-31G(d)). 1,2-Silicon bridging in the transition state for oxygen atom transfer to a nucleophilic amine results in a significant reduction in the barrier height. The barrier for the epoxidation of E-2-butene with bis(dimethyl(trifluoromethyl))silyl peroxide is 25.8 kcal/mol; a reduction of 7.5 kcal/mol relative to epoxidation with 1. The activation energy calculated for the epoxidation of E-2-butene with F(3)SiOOSiF(3) is reduced to only 2.2 kcal/mol reflecting the inductive effect of the electronegative fluorine atoms.     

Exciplex Formation and Excited State Deactivation of Difluoroborondipyrromethene (Bodipy) Dyads

Two series of geometrically‐related dyads are discussed based on the difluoroborondipyrromethene (Bodipy) unit, and incorporating covalently attached hydroquinone/quinone groups. These units are anchored directly, or via a phenylene spacer, to the Bodipy core at the meso position in one series ( BD‐MHQ , BD‐MQ , BD‐MPHQ , BD‐MPQ ), but for the second series the attachment site is the 2‐position ( BD‐SHQ , BD‐SQ , BD‐SPHQ , BD‐SPQ ). The compounds show various levels of fluorescence depending on the oxidation state of the appended group and the substitution pattern. In non‐polar solvents such as toluene, diethyl ether and dichlorobenzene, the S₁ state deactivation of the Bodipy unit in BD‐SPQ and BD‐MPQ is dominated by ^{1, 3}exciplex formation, which has not been reported for Bodipy derivatives so far. In the latter molecule, the decay of the exciplex is divided between population of the Bodipy triplet state (13 %–21 %) and ground state reformation. This partitioning is not seen for the side‐on substituted derivative, BD‐SPQ , and only ground state reformation is observed following decay of the exciplex. This difference in behavior is explained by the radical‐pair inter‐system‐crossing mechanism, which more effectively operates in BD‐MPQ because of the orthogonality of the donor‐acceptor units. In the more polar solvent CH₃CN all the quinone derivatives show fast formation of the charge‐separated state (k_CS) followed by slower charge recombination (k_CR). The ratio k_CS/k_CR≤80.     

Unraveling the Pressure Effect on Nucleation Processes of Amyloidogenic Proteins

The influence of pressure on the nucleation rate of insulin under fibril‐forming conditions was studied and subsequently analysed using classical nucleation theory. The aim was a better understanding and quantification of the influence of pressure on protein aggregation/fibrillation reactions. The application of pressure has a drastic accelerating effect on the nucleation and growth process of insulin fibrils. We show that this effect arises from a volume decrease upon nucleus formation, due to formation of a less hydrated and more compact transition state that can be quantified extending nucleation theory by a pressure–volume term. Conversely, the absolute values of the lag time and the critical size of the nucleus cannot be satisfactorily described by the classical nucleation theory, which might be due to the presence of secondary effects, such as parallel aggregation pathways or fragmentation processes.     

A study into the effect of subtle structural details and disorder on the terahertz spectrum of crystalline benzoic acid

The phonon modes of crystalline benzoic acid have been investigated using terahertz time-domain spectroscopy, rigid molecule atom-atom model potential and plane-wave density functional theory lattice dynamics calculations. The simulation results show good agreement with the measured terahertz spectra and an assignment of the terahertz absorption features of benzoic acid is made with the help of both computational methods. Focussing on the strongest interactions in the crystal, we describe each vibration in terms of distortions of the benzoic acid hydrogen bonded dimers that are present in the crystal structure. The terahertz spectrum is also shown to be highly sensitive to the location of the carboxylic acid hydrogen atoms in the cyclic hydrogen-bonded dimers and we have systematically explored the influence of the observed disorder in the hydrogen atom positions on the lattice dynamics.     

A synchrotron radiation study of the one‐dimensional complex of sodium with (1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d‐ribitol,a member of the 'immucillin' family

The sodium salt of [immucillin‐A–CO₂H]⁻ (Imm‐A), namely catena‐poly[[[triaquadisodium(I)](μ‐aqua)[μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d ‐ribitol][triaquadisodium(I)][μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d ‐ribitol]] tetrahydrate], {[Na₂(C₁₂H₁₃N₄O₆)₂(H₂O)₇]·4H₂O}_n, (I), forms a polymeric chain via Na⁺—O interactions involving the carboxylate and keto O atoms of two independent Imm‐A molecules. Extensive N,O—H...O hydrogen bonding utilizing all water H atoms, including four waters of crystallization, provides crystal packing. The structural definition of this novel compound was made possible through the use of synchrotron radiation utilizing a minute fragment (volume ∼2.4 × 10⁻⁵ mm⁻³) on a beamline optimized for protein data collection. A summary of intra‐ring conformations for immucillin structures indicates considerable flexibility while retaining similar intra‐ring orientations.     

Quinolinone and pyridopyrimidinone inhibitors of DNA-dependent protein kinase

8-Substituted 2-morpholin-4-yl-quinolin-4-ones and 9-substituted 2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-ones with selected aryl and heteroaryl groups as the substituent have been synthesised as potential inhibitors of DNA-dependent protein kinase. A multiple-parallel approach, employing Suzuki cross-coupling methodology, was utilised in the preparation of 8-substituted 2-morpholin-4-yl-quinolin-4-ones. For this purpose 8-bromo-2-morpholin-4-yl-quinolin-4-one was required as an intermediate. This compound was obtained by adapting a literature route in which thermal cyclocondensation of (2-bromoanilino)-morpholin-4-yl-5-methylene-2,2-dimethyl[1,3]dioxane-4,6-dione afforded 8-bromo-2-morpholin-4-yl-quinolin-4-one. A multiple-parallel approach, employing Suzuki cross-coupling methodology, was also utilised to prepare 9-substituted 2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-ones using 9-hydroxy-2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one O-trifluoromethanesulfonate as an intermediate. 8-Substituted 2-morpholin-4-yl-quinolin-4-ones and 9-substituted 2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-ones were both inhibitors of DNA-dependent protein kinase. When the substituent was dibenzothiophen-4-yl, dibenzofuran-4-yl or biphen-3-yl, IC50 values in the low nanomolar range were observed. Interestingly, the pyridopyrimidinones and quinolinones were essentially equipotent with the corresponding 8-substituted 2-morpholin-4-yl-chromen-4-ones previously reported (I. R. Hardcastle, X. Cockcroft, N. J. Curtin, M. Desage El-Murr, J. J. J. Leahy, M. Stockley, B. T. Golding, L. Rigoreau, C. Richardson, G. C. M. Smith and R. J. Griffin, J. Med. Chem., 2005, 48, 7829-7846).     

Influence of Equilibration Time in Solution on the Inclusion/Exclusion Topology Ratio of Host–Guest Complexes Probed by Ion Mobility and Collision‐Induced Dissociation

Host–guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion‐mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host–guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas‐phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para‐phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision‐induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process.     

Redox‐Active Tetraruthenium Macrocycles Built from 1,4‐Divinylphenylene‐Bridged Diruthenium Complexes

Metallamacrocylic tetraruthenium complexes were generated by treatment of 1,4‐divinylphenylene‐bridged diruthenium complexes with functionalized 1,3‐benzene dicarboxylic acids and characterized by HR ESI‐MS and multinuclear NMR spectroscopy. Every divinylphenylene diruthenium subunit is oxidized in two consecutive one‐electron steps with half‐wave potential splittings in the range of 250 to 330 mV. Additional, smaller redox‐splittings between the +/2+ and 0/+ and the 3+/4+ and 2+/3+ redox processes, corresponding to the first and the second oxidations of every divinylphenylene diruthenium entity, are due to electrostatic effects. The lack of electronic coupling through bond or through space is explained by the nodal properties of the relevant molecular orbitals and the lateral side‐by‐side arrangement of the divinylphenylene linkers. The polyelectrochromic behavior of the divinylphenylene diruthenium precursors is retained and even amplified in these metallamacrocyclic structures. EPR studies down to T=4 K indicate that the dications 1‐H²⁺ and 1‐OBu²⁺ are paramagnetic. The dications and the tetracation of macrocycle 3‐H display intense (dications) or weak ( 3‐H⁴⁺ ) EPR signals. Quantum chemical calculations indicate that the four most stable conformers of the macrocycles are largely devoid of strain. Bond parameters, energies as well as charge and spin density distributions of model macrocycle 5‐H^Me were calculated for the different charge and spin states.     

Highly Phosphorescent Crystals of Square‐Planar Platinum Complexes with Chiral Organometallic Linkers: Homochiral versus Heterochiral Arrangements,Induced Circular Dichroism,and TD‐DFT Calculations

A novel class of chiral luminescent square‐planar platinum complexes with a π‐bonded chiral thioquinonoid ligand is described. Remarkably the presence of this chiral organometallic ligand controls the aggregation of this square planar luminophor and imposes a homo‐ or hetero‐chiral arrangement at the supramolecular level, displaying non‐covalent Pt–Pt and π–π interactions. Interestingly these complexes are highly luminescent in the crystalline state and their photophysical properties can be traced to their aggregation in the solid state. A TD‐DFT calculation is obtained to rationalize this unique behavior.