Spin-orbit ab initio investigation of the ultraviolet photolysis of diiodomethane.

The UV photodissociation (<5 eV) of diiodomethane (CH(2)I(2)) is investigated by spin-orbit ab initio calculations. The experimentally observed photodissociation channels in the gas and condensed phases are clearly assigned by multi-state second-order multiconfigurational perturbation theory in conjunction with spin-orbit interaction through complete active space-state interaction potential energy curves. The calculated results indicate that the fast dissociations of the first two singlet states of CH(2)I(2) and CH(2)I--I lead to geminate-radical products, CH(2)I (.)+I((2)P(3/2)) or CH(2)I (.)+ I*((2)P(1/2)). The recombination process from CH(2)I--I to CH(2)I(2) is explained by an isomerization process and a secondary photodissociation reaction of CH(2)I--I. Finally, the study reveals that spin-orbits effects are significant in the quantitative analysis of the electronic spectrum of the CH(2)I--I species.     

A fluorescence-based synthetic LPS sensor

For the detection of bioanalytes, there is an ongoing search for synthetic sensors to replace enzyme-based assays which are sensitive to contaminants or suboptimal storage conditions. Lipopolysaccharide (LPS), a bacteria-borne endotoxin that may lead to life-threatening conditions such as septic shock, is one such case. Fluorescently labeled analogues of two peptide variants derived from the putative ligand-binding domain of the LPS-binding protein CD14 were developed that detect and discriminate LPS and lipids down to the submicromolar concentration range. Peptides are terminally labeled with carboxyfluorescein and tetramethylrhodamine. For one given peptide, sensitivity and specificity for the detection of LPS and discrimination from other lipids are achieved by spectral signatures that combine changes in the fluorescence resonance energy transfer (FRET) between both dyes and the total emission of tetramethylrhodamine. Alternatively, specificity is obtained by combining the FRET efficiencies of both peptide variants. In comparison to published synthetic LPS sensors, the CD14-derived sensors yield an increase in sensitivity by about 3 orders of magnitude and exhibit specificity for analytes for which the design of synthetic recognition elements is a challenging task. Moreover, one of the sensors enabled the detection of LPS in the presence of up to 50% fetal calf serum, thereby demonstrating the feasibility of this peptide-based approach for clinically relevant samples.     

Helical complexes containing diamide-bridged benzene-o-dithiolato/catecholato ligands

The benzene-o-dithiol/catechol ligands H4-2 and H4-3 react with [TiO(acac)2] to give the dinuclear, double-stranded anionic complexes [Ti2(L)2(mu-OCH3)2](2-) ([22](2-), L=2(4-); [23](2-), L=3(4-)). NMR spectroscopic investigations reveal that the complex anion [Ti2(2)2(mu-OCH3)(2)](2-) is formed as a mixture of three of four possible isomers/pairs of enantiomers, whereas only one isomer of the complex anion [Ti2(3)2(mu-OCH3)(2)](2-) is obtained. The crystal structure analysis of (PNP)2[Ti2(3)2(mu-OCH3)2] shows a parallel orientation of the ligand strands, whereas the structure determination for (AsPh4)2[Ti2(2)2(mu-OCH3)2] does not yield conclusive results about the orientation of the ligand strands due the presence of different isomers in solution, the possible co-crystallisation of different isomers and severe disorder in the crystal. NMR spectroscopy shows that ligand H4-3 reacts at elevated temperature with [TiO(acac)2] to give the triple-stranded helicate (PNP)4[Ti2(3)3] ((PNP)4[24]) as a mixture of two isomers, one with a parallel orientation of the ligand strands and one with an antiparallel orientation. Exclusively the triple-stranded helicates [Ti2(L)(3)](4-) ([25](4-), L=1(4-); [26](2-), L=4(4-)) are formed in the reaction of ligands H4-1 and H4-4 with [TiO(acac)2]. The molecular structures of Na(PNP)3[Ti2(1)3]CH(3)OHH(2)OEt(2)O (Na(PNP)3[25]CH(3)OHH(2)OEt(2)O) and Na(1.5)(PNP)(6.5)[Ti2(4)3]2.3 DMF (Na(1.5)(PNP)(6.5)[26]2.3 DMF) reveal a parallel orientation of the ligand strands in both complexes, which is retained in solution. The sodium cations present in the crystal structures lead to two different kinds of aggregation in the solid state. Na-[25]-Na-[25]-Na polymeric chains are formed from compound Na(PNP)3[25], with the sodium cations coordinated by the carbonyl groups of two ligand strands from two different [Ti2(1)3](4-) ions in addition to solvent molecules. In contrast to this, two [Ti2(4)3](4-) ions are connected by a sodium cation that is coordinated by the three meta oxygen atoms of the catecholato groups of each complex tetraanion to form a central {NaO6} octahedron in the anionic pentanuclear complex {[26]-Na-[26]}(7-).     

In silico prediction of drug solubility: 2. Free energy of solvation in pure melts

The solubility of drugs in water is investigated in a series of papers and in the current work. The free energy of solvation, DeltaG*(vl), of a drug molecule in its pure drug melt at 673.15 K (400 degrees C) has been obtained for 46 drug molecules using the free energy perturbation method. The simulations were performed in two steps where first the Coulomb and then the Lennard-Jones interactions were scaled down from full to no interaction. The results have been interpreted using a theory assuming that DeltaG*(vl) = DeltaG(cav) + E(LJ) + E(C)/2 where the free energy of cavity formation, DeltaG(cav), in these pure drug systems was obtained using hard body theories, and E(LJ) and E(C) are the Lennard-Jones and Coulomb interaction energies, respectively, of one molecule with the other ones. Since the main parameter in hard body theories is the volume fraction, an equation of state approach was used to estimate the molecular volume. Promising results were obtained using a theory for hard oblates, in which the oblate axial ratio was calculated from the molecular surface area and volume obtained from simulations. The Coulomb term, E(C)/2, is half of the Coulomb energy in accord with linear response, which showed good agreement with our simulation results. In comparison with our previous results on free energy of hydration, the Coulomb interactions in pure drug systems are weaker, and the van der Waals interactions play a more important role.     

The ion sensitivity of surface conductive single crystalline diamond

Charge build-up at the solid/aqueous interface is a ubiquitous phenomenon that determines the properties of interfacial electrical double layers. Due to its unique properties, the surface of diamond offers an attractive platform to investigate charging mechanisms in aqueous solutions. We investigate the surface charge by studying the ion sensitivity of H-terminated single crystalline diamond surface conductive layers. The effect of monovalent and divalent salts has been probed at different pH values. For a pH above 3.5, increasing the ionic strength results in a decrease of the surface conductivity, in contrast to the results obtained for pH below 3.5. Electrokinetic experiments are in good agreement with the surface conductivity measurements, showing an isoelectric point at pH 3.5 for the H-terminated diamond surface. We discuss the results in terms of the Coulombic screening by electrolyte ions of the surface potential, which is induced by a pH-dependent surface charge. The origin of this surface charge is discussed in terms of charge regulation by amphoteric hydroxyl surface groups and unsymmetrical adsorption of hydroxide and hydronium ions induced by the hydrophobic nature of the H-terminated diamond surface. This surface charge can have important consequences for processes governed by the diamond/aqueous interface, such as electron transfer to charged redox molecules, adsorption of charged molecules and proteins, and ion sensitivity.     

Stereoselective preparation of six diastereomeric quatercyclopropanes from bicyclopropylidene and some derivatives

Diastereomeric meso- and d,l-bis(bicyclopropylidenyl) (5) were obtained upon oxidation with oxygen of a higher-order cuprate generated from lithiobicyclopropylidene (4) in 50 and 31 % yield, respectively. Their perdeuterated analogues meso-[D(14)]- and d,l-[D(14)]-5 were obtained along the same route from perdeuterated bicyclopropylidene [D(8)]-3 (synthesized in six steps in 7.4 % overall yield from [D(8)]-THF) in 20.5 % yield each. Dehalogenative coupling of 1,1-dibromo-2-cyclopropylcyclopropane (6) gave a mixture of all possible stereoisomers of 1,5-dicyclopropylbicyclopropylidene 16 in 69 % yield, from which (Z)-cis-16 was separated by preparative gas chromatography (26 % yield). The crystal structure of meso-5 looks like a superposition of the crystal structures of two outer bicyclopropylidene units (3) and one inner s-trans-bicyclopropyl unit, whereas the two outer cyclopropyl moieties adopt a gauche orientation with respect to the cyclopropane rings at the inner bicyclopropylidene units in (Z)-cis-16. Birch reduction with lithium in liquid ammonia of meso-5 and d,l-5 gave two pairs of diastereomeric quatercyclopropanes trans,trans-(R*,S*,R*, S*)-17/cis,trans-(R*,S*,R*,R*)-18 and trans,trans-(R*,S*,S*,R*)-19/cis,trans-(R*,S*,S*,S*)-20 in 97 and 76 % yield, respectively, in a ratio 9:1 for every pair. The latter diastereomer was also obtained as the sole product by Birch reduction of (Z)-cis-16 in 96 % yield. Under the same conditions, tetradecadeuterio analogues trans,trans-[D(14)]-(R*,S*,R*,S*)-17/cis,trans-[D(14)]-(R*, S*,R*,R*)-18 (8:1) and trans,trans-[D(14)]-(R*,S*,S*,R*)-19/cis,trans-[D(14)]-(R*,S*,S*,S*)-20 (12:1) were prepared from meso-[D(14)]-5 and d,l-[D(14)]-5 in 37 and 63 % yield, respectively. Reduction of meso-5 with diimine gave the cis,cis-quatercyclopropane (S*,S*,R*,R*)-21 as the main product (58 % yield) along with the cis,trans-diastereomer (S*,S*,R*,S*)-18 (29 % yield). Thus, five of the six possible diastereomeric quatercyclopropanes were obtained from meso-5, d,l-5, and (Z)-cis-16. The X-ray crystal structure analyses of trans,trans-(R*,S*,R*,S*)-17 and cis,cis-(S*,S*,R*,R*)-21 revealed for the both an unusual conformation in which the central bicyclopropyl unit adopts an s-trans-(antiperiplanar) orientation with phi=180.0 degrees , and the two terminal bicyclopropyl moieties adopt a synclinal conformation with phi=49.8 and 72.0 degrees , respectively. In solution the vicinal coupling constants (3)J(H,H) in trans,trans-(R*,S*,R*,S*)-[D(14)]-17, trans,trans-(R*,S*,S*,R*)-[D(14)]-19, trans,cis-(R*,S*,R*,R*)-[D(14)]-18 and trans,cis-(R*,S*,S*,S*)-[D(14)]-20 were found to be 4.1, 4.7, 5.9 and 5.9 Hz, respectively. This indicates a predominance of the all-gauche conformer in (R*,S*,R*,S*)-17 and a decreasing fraction of it in this sequence of the other diastereomers.