pH effects on the molecular structure and charging state of b-Escin biosurfactants at the air-water interface

Saponins like b-escin exhibit an unusually high surface activity paired with a remarkable surface rheology which makes them as biosurfactants highly interesting for applications in soft matter colloids and at interfaces. We have applied vibrational sum-frequency generation (SFG) to study b-escin adsorption layers at the air-water interface as a function of electrolyte pH and compare the results from SFG spectroscopy to complementary experiments that have addressed the surface tension and the surface dilational rheology. SFG spectra of b-escin modified air-water interfaces demonstrate that the SFG intensity of OAH stretching vibrations from interfacial water molecules is a function of pH and dramatically increases when the pH is increased from acidic to basic conditions and reaches a plateau at a solution pH of > 6. These changes are attributable to the interfacial charging state and to the deprotonation of the carboxylic acid group of b-escin. Thus, the change in OAH intensity provides qualitative information on the degree of protonation of this group at the air-water interface. At pH < 4 the air-water interface is dominated by the charge neutral form of b-escin, while at pH > 6 its carboxylic acid group is fully deprotonated and, consequently, the interface is highly charged. These observations are corroborated by the change in equilibrium surface tension which is qualitatively similar to the change in OAH intensity as seen in the SFG spectra. Further, once the surface layer is charge neutral, the surface elasticity drastically increases. This can be attributed to a change in prevailing intermolecular interactions that change from dominating repulsive electrostatic interactions at high pH, to dominating attractive interactions, such as hydrophobic and dispersive interactions, as well as, hydrogen bonding at low pH values. In addition to the clear changes in OAH intensity from interfacial H2O, the SFG spectra exhibit drastic changes in the CAH bands from interfacial b-escin which we relate to differences in the net molecular orientation. This orientation change is driven by tighter packing of b-escin adsorption layers when the b-escin moiety is in its charge neutral form (pH < 4).The authors gratefully acknowledge funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 638278).Ye

Synthesis, Spectroscopy and Crystal Structure of a New Copper Complex Built Up by Cationic (Dimethylphosphoryl)methanaminium Ligands

A new transition metal complex of the mono-protonated ligand (dimethylphosphoryl)methanamine (dpmaH+) was obtained by equimolar reaction of copper(II) chloride dihydrate and dpma in concentrated hydrochloric acid. The asymmetric unit of the title structure, [CuCl2(C3H11NOP)4][CuCl4]2, consists of one half of a fourfold charged trans-dichloridotetrakis[(dimethylphosphoryl)methanaminium]copper(II) complex with the copper atom located on an inversion centre and one tetrachloridocuprate(II) dianion found in a general position. The copper centre in the cationic complex shows a tetragonally distorted octahedral environment composed of four oxygen atoms in a square plane and two trans-coordinated chlorido ligands. This 4+2-coordination causes elongated Cu-Cl distances because of the Jahn-Teller effect. The geometry of the tetrachloridocuprate(II) dianion is best described as a seriously distorted tetrahedron. Analysis of the hydrogen bonding scheme by graph-set theory shows three patterns of rings in the title compound. The cationic copper complex reveals intramolecular hydrogen bonds between two aminium groups and the two axial chlorido ligands. Further hydrogen bonding among the cations and anions, more precisely between four aminium groups and the chlorido ligands of four adjacent tetrachloridocuprate(II) anions, lead to a chain-type structure. Comparing the coordination chemistry of the title structure with an analogue cobalt(II) compound only disclose differences in hydrogen bonding pattern resulting in an unusual chain propagation. Besides the crystal structure received spectroscopic data are in accordance with appropriate literature

Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response : a sub-study of the NEAT001/ANRS143 randomized trial

OBJECTIVES: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. METHODS: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. RESULTS: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P < 0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P = 0.269; and 1.82 (0.61-5.41), P = 0.279, respectively]. CONCLUSIONS: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity