Water vapour self-continuum and water dimers: 1. Analysis of recent work

Recent laboratory observations and advances in theoretical quantum chemistry allow a reappraisal of the fundamental mechanisms that determine the water vapour self-continuum absorption throughout the infrared and millimetre wave spectral regions. By starting from a framework that partitions bimolecular interactions between water molecules into free-pair states, true bound and quasi-bound dimers, we present a critical review of recent observations, continuum models and theoretical predictions. In the near-infrared bands of the water monomer, we propose that spectral features in recent laboratory-derived self-continuum can be well explained as being due to a combination of true bound and quasi-bound dimers, when the spectrum of quasi-bound dimers is approximated as being double the broadened spectrum of the water monomer. Such a representation can explain both the wavenumber variation and the temperature dependence. Recent observations of the self-continuum absorption in the windows between these near-infrared bands indicate that widely used continuum models can underestimate the true strength by around an order of magnitude. An existing far-wing model does not appear able to explain the discrepancy, and although a dimer explanation is possible, currently available observations do not allow a compelling case to be made. In the 8–12 micron window, recent observations indicate that the modern continuum models either do not properly represent the temperature dependence, the wavelength variation, or both. The temperature dependence is suggestive of a transition from the dominance of true bound dimers at lower temperatures to quasibound dimers at higher temperatures. In the mid- and far-infrared spectral region, recent theoretical calculations indicate that true bound dimers may explain at least between 20% and 40% of the observed self-continuum. The possibility that quasi-bound dimers could cause an additional contribution of the same size is discussed. Most recent theoretical considerations agree that water dimers are likely to be the dominant contributor to the self-continuum in the mm-wave spectral range.

Mono-aqua-bridged dinuclear complexes of Cu(II) containing NNO donor Schiff base ligand: Hydrogen-bond-mediated exchange coupling

Two new mono-aqua-bridged dinuclear Cu(II) complexes of tridentate NNO Schiff bases, [Cu-2(mu-H2O)L-2(1)(H2O)(2)](BF4)(2)center dot 2H(2)O (1) and [Cu-2(mu-H2O)L-2(2)(H2O)(2)](BF4)(2)center dot 2H(2)O (2) where HL1 = 2-[1-(2-dimethylamino-ethylimino)-ethyl]-phenol and HL2 =2-[(2-dimethylamino-ethylimino)-methyl]-phenol were synthesized. Both the complexes were characterized by single-crystal X-ray diffraction analyses and variable-temperature magnetic measurements. For both the complexes each Cu(II) ion is in a square-pyramidal environment being bonded to three atoms from the tridentate NNO Schiff base and a terminal H2O molecule in the equatorial plane; a second H2O ligand acts as a bridge between the two Cu(II) centres through the axial positions. Hydrogen bonds between the terminal H2O ligand and the Schiff base of the adjacent centre complete the intra-dimer linkages. Variable-temperature (4-300 K) magnetic susceptibility measurement shows the presence of significant antiferromagnetic coupling for both the complexes (J = -12.2 and -12.5 cm(-1), respectively, for 1 and 2), mediated mainly through the intra-dimer H-bonds.

Conformational polymorphism of the molecular complex of 3-fluorobenzoic acid with 4-acetylpyridine

Two polymorphs of the molecular complex formed between 3-fluorobenzoic acid with 4-acetylpyridine are described and found to be based upon the same dimeric supramolecular construct. The conformational freedom around the hydrogen bond results in a 180 degrees rotation about this intermolecular link, distinguishing the polymorphs and affecting the packing of the dimeric units. The two polymorphs are fully characterised by single crystal X-ray and neutron diffraction and quantum mechanical calculations. There is evidence of structured crystal growth defects in both polymorphic crystals via observation of diffuse scattering and a disorder model for the average structure of Form I, which can be interpreted as a mixing of the two dimer conformations. The similarity of energy of the distinct dimeric units, supporting their likely co-existence, has been verified by periodic quantum chemical calculations.

π-dimerization of pleiadiene radical cations at low temperatures revealed by UV–vis spectroelectrochemistry and quantum theory

One-electron oxidation of the non-alternant polycyclic aromatic hydrocarbon pleiadiene and related cyclohepta[ c,d]pyrene and cyclohepta[c,d]fluoranthene in THF produces corresponding radical cations detectable in the temperature range of 293–263 K only on the subsecond time scale of cyclic voltammetry. Although the EPR-active red-coloured pleiadiene radical cation is stable according to the literature in concentrated sulfuric acid, spectroelectrochemical measurements reported in this study provide convincing evidence for its facile conversion into the green-coloured, formally closed shell and, hence, EPRsilent π-bound dimer dication stable in THF at 253 K. The unexpected formation of the thermally unstable dimeric product featuring a characteristic intense low-energy absorption band at 673 nm (1.84 eV; logεmax=4.0) is substantiated by ab initio calculations on the parent pleiadiene molecule and the PF6 − salts of the corresponding radical cation and dimer dication. The latter is stabilized with respect to the radical cation by 14.40 kcal mol−1 (DFT B3LYP) [37.64 kcal mol−1 (CASPT2/DFT B3LYP)]. An excellent match has been obtained between the experimental and TDDFT- calculated UV–vis spectra of the PF6 − salt of the pleiadiene dimer dication, considering solvent (THF) effects.

Corticotropin-releasing factor binding protein dimerizes after association with ligand.

We have suggested recently that the fall in plasma CRF-binding protein (BP) during the last few weeks of pregnancy is a direct effect of association with its ligand because of the rapid decrease in plasma BP concentration seen in normal males reaching a nadir some 15 min after a bolus injection of synthetic CRF. In the present study, we have investigated the physicochemical properties of both natural and recombinant BP by gel filtration under physiological conditions and have shown that association of human CRF to this BP results in an increase in molecular weight consistent with the formation of a dimer form of the BP ligand complex. The dimer is more stable when the interaction occurs in the presence of serum or if a peptide with a higher affinity for the BP is substituted as ligand. Experimental evidence would also suggest that the dimer BP has a higher affinity for ligand than the monomeric form. We suggest that this dimerization occurs in vivo when CRF is released into the bloodstream and provides the trigger that causes the uptake of the complex at specific receptor sites.

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson's disease (PD). LRRK2 contains a Ras of complex proteins (ROC) domain that may act as a GTPase to regulate its protein kinase activity. The structure of ROC and the mechanism(s) by which it regulates kinase activity are not known. Here, we report the crystal structure of the LRRK2 ROC domain in complex with GDP-Mg2+ at 2.0-Å resolution. The structure displays a dimeric fold generated by extensive domain-swapping, resulting in a pair of active sites constructed with essential functional groups contributed from both monomers. Two PD-associated pathogenic residues, R1441 and I1371, are located at the interface of two monomers and provide exquisite interactions to stabilize the ROC dimer. The structure demonstrates that loss of stabilizing forces in the ROC dimer is likely related to decreased GTPase activity resulting from mutations at these sites. Our data suggest that the ROC domain may regulate LRRK2 kinase activity as a dimer, possibly via the C-terminal of ROC (COR) domain as a molecular hinge. The structure of the LRRK2 ROC domain also represents a signature from a previously undescribed class of GTPases from complex proteins and results may provide a unique molecular target for therapeutics in PD.

Functional model for catecholase-like activity: A mechanistic approach with manganese(III) complexes of salen type Schiff base ligands

Three new Mn(III) complexes [MnL1(OOCH)(OH2)] (1), [MnL2(OH2)(2)][Mn2L22(NO2)(3)] (2) and [Mn2L21(NO2)(2)] (3) (where H2L1 = H(2)Me(2)Salen = 2,7-bis(2-hydroxyphenyl)-2,6-diazaocta-2,6-diene and H2L2 = H(2)Salpn = 1,7-bis(2-hydroxyphenyl)-2,6-diazahepta-1,6-diene) have been synthesized. X-ray crystal structure analysis reveals that 1 is a mononuclear species whereas 2 contains a mononuclear cationic and a dinuclear nitrite bridged (mu-1 kappa O:2 kappa O') anionic unit. Complex 3 is a phenoxido bridged dimer containing terminally coordinated nitrite. Complexes 1-3 show excellent catecholase-like activity with 3,5-di-tert-butylcatechol (3,5-DTBC) as the substrate. Kinetic measurements suggest that the rate of catechol oxidation follows saturation kinetics with respect to the substrate and first order kinetics with respect to the catalyst. Formation of bis(mu-oxo)dimanganese(III,III) as an intermediate during the course of reaction is identified from ESI-MS spectra. The characteristic six line EPR spectra of complex 2 in the presence of 3,5-DTBC supports the formation of manganese(II)-semiquinonate as an intermediate species during the catalytic oxidation of 3,5-DTBC.

Synthesis and crystal structures of μ-oxido- and μ-hydroxido-bridged dinuclear iron(III) complexes with an N2O donor ligand - a theoretical study on the influence of weak forces on the Fe-O-Fe bridging angle

The synthesis and crystal structures of three nonheme di-iron(III) complexes with a tridentate N,N,O Schiff-base ligand, 2-({[2-(dimethylamino) ethyl] imino} methyl) phenol (HL), are reported. Complexes [Fe2OL2(NCO)(2)] (1a) and [Fe2OL2(SAL)(2)]center dot H2O [SAL = o-(CHO)C6H4O-] (1b) are unsupported mu-oxido-bridged dimers, and [Fe-2(OH)L-2(HCOO)(2)-(Cl)] (2) is a mu-hydroxido-bridged dimer supported by a formato bridging ligand. All complexes have been characterized by X-ray crystallography and spectroscopic analysis. Complex 1b has been reported previously; however, it has been reinvestigated to confirm the presence of a crucial water molecule in the solid state. Structural analyses show that in 1a the iron atoms are pentacoordinate with a bent Fe-O-Fe angle [142.7(2)degrees], whereas in 2 the metal centers are hexacoordinate with a normal Fe-OH-Fe bridging angle [137.9(2)degrees]. The Fe-O-Fe angles in complexes 1a and 1b differ significantly to those usually shown by (mu-oxido) Fe-III complexes. A theoretical study has been performed in order to rationalize this deviation. Moreover, the influence of the water molecule observed in the solid-state structure of 1b on the Fe-O-Fe angle is also analyzed theoretically.

Anion-directed template synthesis and hydrolysis of mono-condensed Schiff base of 1,3-pentanediamine ando-hydroxyacetophenone in NiII and CuII Complexes

Bis(o-hydroxyacetophenone)nickel(II) dihydrate, on reaction with 1,3-pentanediamine, yields a bis-chelate complex [NiL2]·2H2O (1) of mono-condensed tridentate Schiff baseligand HL {2-[1-(3-aminopentylimino)ethyl]phenol}. The Schiff base has been freed from the complex by precipitating the NiII as a dimethylglyoximato complex. HL reacts smoothly with Ni(SCN)2·4H2O furnishing the complex [NiL(NCS)] (2) and with CuCl2·2H2O in the presence of NaN3 or NH4SCN producing [CuL(N3)]2 (3) or [CuL(NCS)] (4). On the other hand, upon reaction with Cu(ClO4)2·6H2O and Cu(NO3)2·3H2O, the Schiff base undergoes hydrolysis to yield ternary complexes [Cu(hap)(pn)(H2O)]ClO4 (5) and [Cu(hap)(pn)(H2O)]NO3 (6), respectively (Hhap = o-hydroxyacetophenone and pn = 1,3-pentanediamine). The ligand HL undergoes hydrolysis also on reaction with Ni(ClO4)2·6H2O or Ni(NO3)2·6H2O to yield [Ni(hap)2] (7). The structures of the complexes 2, 3, 5, 6, and 7 have been confirmed by single-crystal X-ray analysis. In complex 2, NiII possesses square-planar geometry, being coordinated by the tridentate mono-negative Schiff base, L and the isothiocyanate group. The coordination environment around CuII in complex 3 is very similar to that in complex 2 but here two units are joined together by end-on, axial-equatorial azide bridges to result in a dimer in which the geometry around CuII is square pyramidal. In both 5 and 6, the CuII atoms display the square-pyramidal environment; the equatorial sites being coordinated by the two amine groups of 1,3-pentanediamine and two oxygen atoms of o-hydroxyacetophenone. The axial site is coordinated by a water molecule. Complex 7 is a square-planar complex with the Ni atom bonded to four oxygen atoms from two hap moieties. The mononuclear units of 2 and dinuclear units of 3 are linked by strong hydrogen bonds to form a one-dimensional network. The mononuclear units of 5 and 6 are joined together to form a dimer by very strong hydrogen bonds through the coordinated water molecule. These dimers are further involved in hydrogen bonding with the respective counteranions to form 2-D net-like open frameworks.

Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation

CONTEXT: The link between long-haul air travel and venous thromboembolism is the subject of continuing debate. It remains unclear whether the reduced cabin pressure and oxygen tension in the airplane cabin create an increased risk compared with seated immobility at ground level. OBJECTIVE: To determine whether hypobaric hypoxia, which may be encountered during air travel, activates hemostasis. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, crossover study, performed in a hypobaric chamber, to assess the effect of an 8-hour seated exposure to hypobaric hypoxia on hemostasis in 73 healthy volunteers, which was conducted in the United Kingdom from September 2003 to November 2005. Participants were screened for factor V Leiden G1691A and prothrombin G20210A mutation and were excluded if they tested positive. Blood was drawn before and after exposure to assess activation of hemostasis. INTERVENTIONS: Individuals were exposed alternately (> or =1 week apart) to hypobaric hypoxia, similar to the conditions of reduced cabin pressure during commercial air travel (equivalent to atmospheric pressure at an altitude of 2438 m), and normobaric normoxia (control condition; equivalent to atmospheric conditions at ground level, circa 70 m above sea level). MAIN OUTCOME MEASURES: Comparative changes in markers of coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation. RESULTS: Changes were observed in some hemostatic markers during the normobaric exposure, attributed to prolonged sitting and circadian variation. However, there were no significant differences between the changes in the hypobaric and the normobaric exposures. For example, the median difference in change between the hypobaric and normobaric exposure was 0 ng/mL for thrombin-antithrombin complex (95% CI, -0.30 to 0.30 ng/mL); -0.02 [corrected] nmol/L for prothrombin fragment 1 + 2 (95% CI, -0.03 to 0.01 nmol/L); 1.38 ng/mL for D-dimer (95% CI, -3.63 to 9.72 ng/mL); and -2.00% for endogenous thrombin potential (95% CI, -4.00% to 1.00%). CONCLUSION: Our findings do not support the hypothesis that hypobaric hypoxia, of the degree that might be encountered during long-haul air travel, is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.

Radical cations of end-capped tetrathienoacenes and their p-dimerization controlled by the nature of a-substituents and counterion concentration

Radical cations of a soluble rigid tetrathienoacene are capable of forming stable p-dimer dications at ambient temperature when the short backbone becomes extended with conjugated thiophene-2-yl substituents in the a-positions. On the other hand, simple attachment of methyl groups on the a-carbon of the external thiophen-2-yl rings proved sufficient to inhibit the dimerization. Stable radical cationswere also exclusively formed for tetrathienoacene derivatives end-capped with bulky TIPS and phenyl substituents.

Spectroelectrochemical study of complexes [Mo(CO)2(h3-allyl)(adiimine)(NCS)] (a-diimine ¼ bis(2,6-dimethylphenyl)- acenaphthenequinonediimine and 2,20-bipyridine) exhibiting different molecular structure and redox reactivity

The redox properties and reactivity of [Mo(CO)2(η3-allyl)(α-diimine)(NCS)] (α-diimine = bis(2,6-dimethylphenyl)-acenaphthenequinonediimine (2,6-xylyl-BIAN) and 2,2′-bipyridine (bpy)) were studied using cyclic voltammetry and IR/UV–Vis spectroelectrochemistry. [Mo(CO)2(η3-allyl)(2,6-xylyl-BIAN)(NCS)] was shown by X-ray crystallography to have an asymmetric (B-type) conformation. The extended aromatic system of the strong π-acceptor 2,6-xylyl-BIAN ligand stabilises the primary 1e−-reduced radical anion, [Mo(CO)2(η3-allyl)(2,6-xylyl-BIAN•−)(NCS)]−, that can be reduced further to give the solvento anion [Mo(CO)2(η3-allyl)(2,6-xylyl-BIAN)(THF)]−. The initial reduction of [Mo(CO)2(η3-allyl)(bpy)(NCS)] in THF at ambient temperature results in the formation of [Mo(CO)2(η3-allyl)(bpy)]2 by reaction of the remaining parent complex with [Mo(CO)2(η3-allyl)(bpy)]− produced by dissociation of NCS− from [Mo(CO)2(η3-allyl)(bpy•−)(NCS)]−. Further reduction of the dimer [Mo(CO)2(η3-allyl)(bpy)]2 restores [Mo(CO)2(η3-allyl)(bpy)]−. In PrCN at 183 K, [Mo(CO)2(η3-allyl)(2,6-xylyl-BIAN•−)(NCS)]− converts slowly to 2e−-reduced [Mo(CO)2(η3-allyl)(2,6-xylyl-BIAN)(PrCN)]− and free NCS−. At room temperature, the reduction path in PrCN involves mainly the dimer [Mo(CO)2(η3-allyl)(bpy)]2; however, the detailed course of the reduction within the spectroelectrochemical cell is complicated and involves a mixture of several unassigned products. Finally, it has been shown that the five-coordinate anion [Mo(CO)2(η3-allyl)(bpy)]− promotes in THF reduction of CO2 to CO and formate via the formation of the intermediate [Mo(CO)2(η3-allyl)(bpy)(O2CH)] and its subsequent reduction.

Multistep π dimerization of tetrakis(n-decyl)heptathienoacene radical cations: a combined experimental and theoretical study

Radical cations of a heptathienoacene a,b-substituted with four n-decyl side groups (D4T7C+) form exceptionally stable p-dimer dications already at ambient temperature (Chem. Comm. 2011, 47, 12622). This extraordinary p-dimerization process is investigated here with a focus on the ultimate[D4T7C+]2 p-dimer dication and yet-unreported transitoryspecies formed during and after the oxidation. To this end, we use a joint experimental and theoretical approach that combines cyclic voltammetry, in situ spectrochemistry and spectroelectrochemistry, EPR spectroscopy, and DFT calculations. The impact of temperature, thienoacene concentration, and the nature and concentration of counteranions on the p-dimerization process is also investigated in detail. Two different transitory species were detected in the course of the one-electron oxidation: 1) a different transient conformation of the ultimate [D4T7C+]2 p-dimer dications, the stability of which is strongly affected by the applied experimental conditions, and 2) intermediate [D4T7]2C+ p-dimer radical cations formed prior to the fully oxidized [D4T7]2C+ p-dimer dications. Thus, this comprehensive work demonstrates the formation of peculiar supramolecular species of heptathienoacene radical cations, the stability, nature, and structure of which have been successfully analyzed. We therefore believe that this study leads to a deeper fundamental understanding of the mechanism of dimer formation between conjugated aromatic systems.

Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers’ disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly “nanodisc” structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/ Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.

Redox- and glucose-responsive hydrogels from poly(vinyl alcohol) and 4-mercaptophenylboronic acid

Novel redox- and glucose-responsive hydrogels have been synthesized by simple mixing of poly(vinyl alcohol) (PVA) and 4-mercaptophenylboronic acid (MPBA) in aqueous solutions (pH > 9) in an oxidative aqueous media. These hydrogels are produced through the formation of disulfide linkages between MPBA molecules in an oxidative environment (oxygen dissolved in solution or hydrogen peroxide added to the reaction mixture) and complexation via dynamic covalent bonds between PVA and MPBA dimer. These hydrogels show degradation in solutions of l-glutathione and d-glucose.