Spectroscopy, binding to liposomes and production of singlet oxygen by porphyrazines with modularly variable water solubility

Three novel classes of porphyrazine-like structures were synthesized to form modular structures in which lipophilicity and water solubility can be tuned. Subtle modification of solubility is an important criterion in selecting a compound for biological photosensitization. The general structure takes the form H2[pz(AnB4-n)], where the core is a porphyrazine (pz) group, A is a pyrrole ring with two sulfide linkages (SR moieties) and B is a pyrrole fused with a 4,7-bis(isopropyloxy)benzo group, with n=4, 3 and 2. These molecules possess their longest wavelength absorption band between 700 and 810 nm, hence laser beams of higher tissue penetration depth could be used to illuminate them in photodynamic therapy (PDT). Armed with absorption bands in the far-red and near-infrared (near-IR), and a capability to tune the solubility, these molecules could make for better sensitizers because of optimized uptake by lipidic membranes and better optical properties. We tested several derivatives of the A4, A3B and A2B2 structures for their singlet oxygen quantum yields in methanol and in liposomes, using 9,10-dimethyl anthracene (DMA) as a singlet oxygen target. Singlet oxygen quantum yields in liposomes ranged from 0.01 to 0.44, with the A2B2 group showing the most promise. In the binding assay to find the equilibrium binding constant, Kb, we detected fluorescence changes due to a change in environment. Peripheral long-chain moieties (the R group in the SR moieties) dominate lipid binding. These moieties range in the hydrophobicity that they induce from C8H17 and benzene, which rendered the molecule totally insoluble in water, to polyethylene glycol (PEG) and carboxylate groups, which imparted water solubility. Each molecule had between 4 and 8 such identical chains. Chains bearing an ether or ester link resulted in measurable equilibrium constants, with a higher Kb for ether substituents. Results for Kb ranged from 0.23 to 26.52 (mg mL(-1))(-1). A delicate balance exists between water solubility and good partitioning to membranes. In general, a higher oxygen-to-carbon ratio in the chains improves binding. Fewer chains and a centrally coordinated zinc ion further improve binding and singlet oxygen production.     

A behavioral model for estimating population exposure to solar ultraviolet radiation

Determining the variability of solar UV exposure of different members of a population by direct measurement demands high compliance over an extended period of time by a large number of people. An alternative approach is to model the variables that affect personal exposure and this is the basis of the method reported here, which uses a random sampling technique to explore variability of exposure at different times of the year by habitués. It is shown that there are large variations in daily personal erythemal exposure, more so for indoor workers living in northern Europe than those resident in Florida, which are due not only to seasonal changes in ambient, but just as importantly to seasonal variation in behavior. Not surprisingly, holiday and summer weekend exposure account for the largest daily UV doses. Northern Europeans who take their summer vacation in Florida can double their exposure during this period compared with holidaying at home and this illustrates just how important sun protection measures should be during recreational exposure in areas of high insolation if the annual UV burden is to be sensibly controlled.     

Heterobimetallic Complexes: Substitution Effects in the [Tetracarbonylrhodiumbis{μ‐(diphenylphosphino)}{μ‐(η:η2‐(4‐diphenylphosphino‐κP)‐2‐methyl‐oxobutyl)}molybdenum](Mo‐Rh) System

Syntheses of the array of heterobimetallic complexes [(OC)₃M(μ‐PPh₂)₂(μ‐O‐C(CHMe(CH₂)₂PPh₂)RhL], M = Cr, Mo, W, L = ^tBuNC, are described, extending the previous study of the counterpart array for L = CO. A single crystal X‐ray structure determination is reported for the M = Mo adduct, enabling comparison with its previously reported L = CO counterpart, for which an improved redetermination is also reported. In the present complex the ^tBuNC ligand is found to be much more weakly bound (Rh‐C 2.026(5) Å) than the carbonyl group it displaces (Rh‐C 1.945(2) Å) with concomitant minor impact on the remainder of the rhodium ambience.     

Zeta potential and electroosmotic mobility in microfluidic devices fabricated from hydrophobic polymers: 2. Slip and interfacial water structure

We discuss the structure of water at hydrophobic interfaces from the standpoint of its impact on electrokinetic phenomena in microfluidic devices fabricated from hydrophobic polymers such as Teflon or Zeonor. Water structuring at hydrophobic interfaces has been described as a source of interfacial charge (see Part 1, this issue), and dewetting phenomena, whether via depletion layers or nanobubbles, contribute to slip and enhanced apparent electrokinetic potentials. Issues concerning the impact of hydrodynamic slip and the role of diffuse interfacial structures are discussed. These issues are coupled with each other and with interfacial charge concerns, providing challenges for measurements of individual parameters.     

A simple and cost effective method for the quantification of 8-hydroxy-2'-deoxyguanosine from urine using liquid chromatography tandem mass spectrometry

A rapid and high-throughput method for the determination of urinary levels of the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), has been developed and validated using liquid chromatography combined with electrospray ionization tandem mass spectrometry (LC-MS/MS). The assay features a cheap and readily available non-isotopic internal standard, a single-step filtration sample preparation, and a total analysis time of 6 min including column re-equilibration. The method was validated based on linearity, accuracy (100-106%), precision (CV < 7%), sample preparation stability (< or =5%, 72 h). Intra-laboratory patient ranges were established comparing children and adults (n = 345).     

Mechanism of nanocapsules formation by the emulsion-diffusion process

A detailed investigation into the mechanisms of nanocapsule formation by means of the two stages "emulsion-diffusion" process is reported. Such widely used process is still poorly understood. An emulsion of oil, polymer and ethyl acetate is fabricated as a first step; dilution with pure water allows ethyl acetate to diffuse out from the droplets, leaving a suspension of nanocapsules at the end. It has been shown that the size of nanocapsules was related to the chemical composition of the organic phase and the size of primary emulsion through a simple geometrical relationship. As a consequence, most of the properties of the nanocapsules were decided at the emulsification step. The influence of several formulation and processing parameters of the primary emulsion was studied accordingly. The thin polymer membrane of nanocapsules was observed by means of cryo-fracture electron microscopy. Finally two experiments were designed for a mechanistic investigation of the diffusion step. A step-by-step diffusion of the organic solvent takes place by successive partition equilibria of ethyl acetate between the droplets and aqueous phase. A time-resolved experiment shows the fast diffusion (less than 20 ms) related to the small droplet size of the emulsion.     

Hydride reduction of NAD+ analogues by isopropyl alcohol: kinetics, deuterium isotope effects and mechanism

Observed pseudo-first-order rate constants (k(obs)) of the hydride-transfer reactions from isopropyl alcohol (i-PrOH) to two NAD(+) analogues, 9-phenylxanthylium ion (PhXn(+)) and 10-methylacridinium ion (MA(+)), were determined at temperatures ranging from 49 to 82 degrees C in i-PrOH containing various amounts of AN or water. Formations of the alcohol-cation ether adducts (ROPr-i) were observed as side equilibria. The equilibrium constants for the conversion of PhXn(+) to PhXnOPr-i in i-PrOH/AN (v/v = 1) were determined, and the equilibrium isotope effect (EIE = K(i-PrOH)/K(i-PrOD)) at 62 degrees C was calculated to be 2.67. The k(H) of the hydride-transfer step for both reactions were calculated on the basis of the k(obs) and K. The corresponding deuterium kinetic isotope effects (e.g., KIE(OD)(H) = k(H)(i-PrOH)/k(H)(i-PrOD) and KIE(beta-D6)(H) = k(obs)(i-PrOH)/k(obs)((CD3)2CHOH)), as well as the activation parameters, were derived. For the reaction of PhXn(+) (62 degrees C) and MA(+) (67 degrees C), primary KIE(alpha-D)(H) (4.4 and 2.1, respectively) as well as secondary KIE(OD)(H) (1.07 and 1.18) and KIE(beta-D6)(H) (1.1 and 1.5) were observed. The observed EIE and KIE(OD)(H) were explained in terms of the fractionation factors for deuterium between OH and OH(+)(OH(delta+)) sites. The observed inverse kinetic solvent isotope effect for the reaction of PhXn(+) (k(obs)(i-PrOH)/k(obs)(i-PrOD) = 0.39) is consistent with the intermolecular hydride-transfer mechanism. The dramatic reduction of the reaction rate for MA(+), when the water or i-PrOH cosolvent was replaced by AN, suggests that the hydride-transfer T.S. is stabilized by H-bonding between O of the solvent OH and the substrate alcohol OH(delta+). This result suggests an H-bonding stabilization effect on the T.S. of the alcohol dehydrogenase reactions.     

Azolium-linked cyclophanes: effects of structure, solvent, and counteranions on solution conformation behavior

This paper describes the synthesis, structural characterization, and solution behavior of some xylyl-linked imidazolium and benzimidazolium cyclophanes decorated with alkyl or alkoxy groups. The addition of alkyl/alkoxy chains to the cyclophanes allows for studies in chlorinated solvents, whereas previous solution studies of azolium cyclophanes have generally required highly polar solvents. The azolium cyclophanes may exist in a syn/syn conformation (azolium rings mutually syn, arene rings mutually syn) or a syn/anti conformation (azolium rings mutually syn, arene rings mutually anti). The preferred conformation is significantly affected by (i) binding of bromide (ion pairing) to the protons on the imidazolium or benzimidazolium rings, which occurs in solutions of bromide salts of the cyclophanes in chlorinated solvents, and (ii) the addition of alkoxy groups to the benzimidazolium cyclophanes. These structural modifications have also led to cyclophanes that adopt conformations not previously identified for similar azolium cyclophane analogues. Detailed (1)H NMR studies for one cyclophane identified binding of bromide at two independent sites within the cyclophane.     

Syntheses and molecular structures of some compounds containing many-atom chains end-capped by tricobalt carbonyl clusters

Several complexes containing Co₃ carbonyl clusters end-capping carbon chains of various lengths are described. Pd(0)/Cu(I)-catalysed reactions between {Co₃{μ₃-C(CC)₂Au(PPh₃)}(μ-dppm)(CO)₇ and I(CC)₂SiMe₃ or FcCCI gave {Co₃{μ₃-C(CC)_xR}(μ-dppm)(CO)₇ [x = 4, R = SiMe₃3; x = 3, R = Fc 8]; treatment of 3 with NaOMe and AuCl(PPh₃) gave 4 [x = 4, R = Au(PPh₃)]. Related preparations of Co₃{μ₃-C(CC)₂[Ru(PP)Cp′]}(μ-dppm)_n(CO)_9−2n [PP = (PPh₃)₂, Cp’ = Cp, n = 1, 5; PP = dppe, Cp′ = Cp^∗, n = 1, 6; 0, 7] are also described. Syntheses of bis-cluster complexes {Co₃(μ-dppm)(CO)₇}₂(μ-C_x) (x = 14, 12; 16, 9; 18, 11; 26, 10) - the latter being the longest cluster-capped C_x chains so far described - and the mercury-bridged compounds Hg{(CC)_xC[Co₃(μ-dppm)(CO)₇]}₂ (x = 1, 13; 2, 14) are reported. The molecular structures of 7, 12, 13 and 14, as well as of Co₃(μ₃-CCCSiMe₃)(μ-dppm)(CO)₆(PPh₃) (15) and Co₃{μ₃-CC(O)OEt}(μ-dppm)(CO)₇ (16), are reported.