CFC phase-out: have we met the challenge?

In 1974 Nobel prize winners Rowland and Molina proposed that chlorofluorocarbons (CFCs) were stable enough to reach the stratosphere, where, under intense solar radiation they released Cl atoms that could destroy stratospheric ozone protecting the earth’s surface from UV rays. The CFC industry funded both scientific studies to test the Rowland and Molina hypothesis and programmes to identify potential replacements, from which the HFCs emerged as likely candidates. After 5 years it was concluded, on the best scientific evidence available, that stratospheric ozone was being depleted at ∼3% per decade, but sufficient time was available for an orderly phase-out. Although the USA and a few other countries stopped the use of CFCs in aerosols little further work was done until 1985 when the CFC debate was renewed following the discovery of stratospheric ozone depletion over the Antarctic during its spring. Manufacturers restarted their R&D programmes; governments negotiated the Montreal Protocol in 1987 agreeing the partial phase-out of the CFCs. As a result of subsequent amendments CFCs have now been phased-out in the developed world and HCFCs will follow over the next two decades. This paper reviews what has been achieved and what remains to be done. Has the world-wide effort been successful in protecting the ozone layer? Have “acceptable” alternatives been found for the CFCs/HCFCs in their various applications?     

CFC and Halon replacements in the environment

Substitute fluorocarbons may have direct environmental impact, for example as greenhouse gases, or indirect impacts through the products of their decomposition in the environment. The mechanisms of that atmospheric decomposition are reviewed here and shown to be well established now. The end products are halogen acids and trifluoroacetic acid, all of which pre-exist in the environment in quantities greater than are expected to arise from fluorocarbon use and emissions. Furthermore, the growth in use of fluorocarbon replacements has been shown to be far less than the fall in CFC and Halon production. Hydrochlorofluorocarbons (HCFCs) have replaced less than one third of CFCs and are, themselves, ozone depleting substances that will be phased out under the Montreal Protocol. The growth in hydrofluorocarbons (HFCs) amounts to about 10% of the fall in CFCs. It is likely that the impact of new fluorocarbons on climate change will be a very small fraction of the total impact, which comes mainly from the accumulation of carbon dioxide in the atmosphere.     

Monitoring arsenic in the environment: a review of science and technologies with the potential for field measurements

This review examines available field assays and other technologies with the potential to measure and monitor arsenic in the environment. The strengths and weaknesses of the various assays are discussed with respect to their sensitivity, ability to detect the chemical states of arsenic, performance in various media, potential interferences, and ease of operation. The state of the science and development efforts of selected technologies is presented.     

Deamination process in the formation of a copper(II) complex with glutamic acid and a new ligand derived from guanidinoacetic acid: Synthesis,characterization, and molecular modeling studies

A deamination process was observed after copper(II) complexation reaction with guanidinoacetic (Gaa) and glutamic acids (Glu), forming the binuclear copper(II) complex K₂Cu₂C₁₆H₂₃N₇O₁₂ · 1/2H₂O (1), which was characterized by elemental analysis (CHN), spectroscopy methods (IR and EPR), powder X-ray diffraction, thermogravimetric analysis (TGA), and mass spectrometry. A new ligand, namely biguanide-1,5-diethanoate (Bge) (C₆H₉N₅O₄), was formed during complexation, probably due to the reaction between two Gaa species and the consequent release of a significant amount of ammonia, thus, characterizing the deamination process. In complex 1, Bge behaved as a tetradentated ligand, using its oxygen and nitrogen atoms as coordinating sites to both Cu(II) ions. In addition, Glu has coordinated to Cu(II) through its α-N and O atoms. Theoretical calculations of the cis–cis, cis–trans, and trans–trans isomers of 1, considering three prototropic forms of the Bge ligand, were carried out using semi-empirical quantum mechanics (PM3/d). DFT (B3LYP and B3P86) calculations of complex 1, in which a hydrogen atom replaced the side chain of Glu, were also carried out using the 6-31G(d) basis set and the LanL2DZ effective core potential for the transition metal. Based on experimental and theoretical data, we concluded that the trans–trans isomer of the binuclear copper(II) complex 1 should be the most stable, although the occurrence of other isomers, even if in minor quantities, should not be disregarded.     

Chemical oxidation of a redox-active, ferrocene-containing cationic lipid: Influence on interactions with DNA and characterization in the context of cell transfection

We report an approach to the chemical oxidation of a ferrocene-containing cationic lipid [bis(11-ferrocenylundecyl)dimethylammonium bromide, BFDMA] that provides redox-based control over the delivery of DNA to cells. We demonstrate that BFDMA can be oxidized rapidly and quantitatively by treatment with Fe(III)sulfate. This chemical approach, while offering practical advantages compared to electrochemical methods used in past studies, was found to yield BFDMA/DNA lipoplexes that behave differently in the context of cell transfection from lipoplexes formed using electrochemically oxidized BFDMA. Specifically, while lipoplexes of the latter do not transfect cells efficiently, lipoplexes of chemically oxidized BFDMA promoted high levels of transgene expression (similar to levels promoted by reduced BFDMA). Characterization by SANS and cryo-TEM revealed lipoplexes of chemically and electrochemically oxidized BFDMA to both have amorphous nanostructures, but these lipoplexes differed significantly in size and zeta potential. Our results suggest that differences in zeta potential arise from the presence of residual Fe²⁺ and Fe³⁺ ions in samples of chemically oxidized BFDMA. Addition of the iron chelating agent EDTA to solutions of chemically oxidized BFDMA produced samples functionally similar to electrochemically oxidized BFDMA. These EDTA-treated samples could also be chemically reduced by treatment with ascorbic acid to produce samples of reduced BFDMA that do promote transfection. Our results demonstrate that entirely chemical approaches to oxidation and reduction can be used to achieve redox-based ‘on/off’ control of cell transfection similar to that achieved using electrochemical methods.     

Molecular dynamics study of host–guest interactions in cyclodextrins: methodology and data analysis for a comparison with solution data and the solid-state structure

A general method is proposed to model the behavior of cyclodextrins (CDs) and of their inclusion compounds through energy minimizations and molecular dynamics (MD) simulations at a constant temperature. In this way, the formation of a host–guest compound is obtained starting from many trial geometries with the guest outside the CD cavity without any a priori assumption. The MD simulation results are analyzed through two functions: (i) the similarity maps of the root-mean-square distances between instantaneous conformations found in the MD runs to recognize different families of conformers; (ii) the pair distribution function PDF, yielding the probability density of finding appropriate atom pairs as a function of their distance at equilibrium. As an example, the inclusion compound formed by β-CD and (−)-menthol-β-d-glucoside is investigated. The lowest-energy inclusion compound is in good agreement with the results of single-crystal X-ray analysis, while at room temperature the MD runs show a closely similar arrangement with thermal fluctuations. In this case, the PDF between diagnostic hydrogen atoms of β-CD and of the guest molecule are fully consistent with the experimental NOE results obtained from NMR measurements in solution.     

Non-innocent behaviour of imido ligands in the reactions of silanes with half-sandwich imido complexes of Nb and V: a silane/imido coupling route to compounds with nonclassical Si--H interactions

Reactions of imido complexes [M(Cp)(=NR')(PR'3)2] (M=V, Nb) with silanes afford a plethora of products, depending on the nature of the metal, substitution at silicon and nitrogen and the steric properties of the phosphine. The main products are [M(Cp)(=NR')(PR3)(H)(SiRnCl3-n)] (M=V, Nb; R'=2,6-diisopropylphenyl (Ar), 2,6-dimethylphenyl (Ar')), [Nb(Cp)(=NR')(PR'3)(H)(SiPhR2)] (R2=MeH, H2), [Nb(Cp)(==NR')(PR'3)(Cl)(SiHRnCl2-n)] and [Nb(Cp)(eta 3-N(R)SiR2--H...)(PR'3)(Cl)]. Complexes with the smaller Ar' substituent at nitrogen react faster, as do more acidic silanes. Bulkier groups at silicon and phosphorus slow down the reaction substantially. Kinetic NMR experiments supported by DFT calculations reveal an associative mechanism going via an intermediate N-silane adduct [Nb(Cp){=N(-->SiHClR2)R'}(PR'3)2] bearing a penta-coordinate silicon centre, which then rearranges into the final products through a Si--H or Si--Cl bond activation process. DFT calculations show that this imido-silane adduct is additionally stabilized by a Si--HM agostic interaction. Si--H activation is kinetically preferred even when Si--Cl activation affords thermodynamically more stable products. The niobium complexes [NbCp(=NAr)(PMe3)(H)(SiR2Cl)] (R=Ph, Cl) are classical according to X-ray studies, but DFT calculations suggest the presence of interligand hypervalent interactions (IHI) in the model complex [Nb(Cp) (==NMe)(PMe3)(H)(SiMe2Cl)]. The extent of Si--H activation in the beta-Si--HM agostic complexes [Cp{eta 3-N(R')SiR2--H}M(PR'3)(Cl)] (R'=PMe3, PMe2Ph) primarily depends on the identity of the ligand trans to the Si--H bond. A trans phosphine leads to a stronger Si--H bond, manifested by a larger J(Si--H) coupling constant. The Si--H activation diminishes slightly when a less basic phosphine is employed, consistent with decreased back-donation from the metal.     

Controlled/living cationic polymerization of styrene with BF3OEt2 as a coinitiator in the presence of water: Improvements and limitations

The controlled/living cationic polymerization of styrene using R-OH/BF₃OEt₂ (R-OH = 1-phenylethanol (1), 2-phenyl-2-propanol (2) and 1-(4-methoxyphenyl)ethanol (3)) at 0 °C in CH₂Cl₂ and in the presence of water was investigated. With 1/BF₃OEt₂, the poor control over molecular weight and molecular weight distribution was ascribed to a competitive protonic initiation induced by water. The molecular weight of the polymers obtained with 2/BF₃OEt₂ and 3/BF₃OEt₂ at low water content ([H₂O] ? 0.11 M) increased in direct proportion to the monomer conversion in agreement with the calculated values, assuming that one initiator molecule generates one polymer chain, but the molecular weight distribution was found relatively broad (M_w/M_n ∼ 1.8). ¹H NMR analyses confirmed that polymerization proceeds via reversible activation of C-OH terminus, but some loss of hydroxyl functionality was revealed. Some trials using high water contents in the recipe ([H₂O] ? 1.6 M) produced only traces of polymer due to catalyst decomposition.     

Alternating current anodic stripping voltammetry in the study of cadmium complexation by a reference Suwannee river fulvic acid: a model case with strong electrode adsorption and weak binding

The possibilities of anodic stripping voltammetry (ASV) using an alternating current (AC) scan in the stripping step have been checked through the study of the complexation of cadmium by Suwannee river fulvic acid (SRFA), a reference fulvic acid from the International Humic Substances Society. Because of the strong electrode adsorption of SRFA, AC mode appears to be a good approach to the study when proper selection of the phase angle is made. The goodness of AC mode in ASV has been demonstrated, and the complexation constant of 3.71 ± 0.04 determined is in good agreement with the value of the constant obtained by the reference technique of reverse pulse polarography. Some particularities of SRFA have been observed, among them its homofunctional and strongly heterogeneous behaviour in cadmium complexation and the impossibility of avoiding electrode adsorption problems in ASV measurements at very low metal concentrations. Figure DP anodic stripping and AC anodic stripping voltammograms at −12° and −65° during the titration of a 10⁻⁷ mol L⁻¹ Cd(II) solution with SRFA at pH 7.5 in 0.05 L⁻¹ Tris Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

In vitro cytochrome P450 activity: development and validation of a sensitive high performance liquid chromatography-tandem mass spectrometry method for the quantification of six probe metabolites after derivatization with pyridine-3-sulfonyl chloride in an aqueous environment

For the determination of the in vitro cytochrome P450 activity in microsomes, a quantification method for the probe metabolites, formed during incubation, is required. Due to insufficient sensitivity of a previously developed high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for some of the metabolites, a fast and easy derivatization method with pyridine-3-sulfonyl chloride (PS) is described. Acetaminophen (CYP1A2), dextrorphan (CYP2D6), hydroxy-chlorzoxazone (CYP2E1) and hydroxy-mephenytoin (CYP2C19) can be derivatized because of the presence of a phenolic OH, whereas hydroxy-midazolam (CYP3A4) and hydroxy-tolbutamide (CYP2C9) remain unchanged. As PS improves the ionization efficiency in the positive electrospray ionization (ESI) mode, the sensitivity of the detection is improved significantly and meets requirements for the activity determination. Native negative electrospray type molecules, moreover, become positive ESI candidates. The direct derivatization in the aqueous incubation medium, without any other sample pre-treatment steps, such as evaporation or extraction, makes this procedure easy to perform. The method using 20s microwave irradiation was shown to equal a 10min reaction in a 60°C heating block, consequently simplifying and shortening the process. Collision induced fragmentation of the derivatives resulted in at least one native compound, rather than derivative, specific product ion, thereby improving the selectivity of the method in the multiple reaction monitoring mode. The HPLC-MS/MS method was validated, and was demonstrated to be sensitive, selective, precise and accurate. The absence of a relative matrix effect was established, notwithstanding that an absolute matrix effect was observed. The analysis of a sample after microsomal incubation, from which some of the metabolites could not be quantified using the method without derivatization, proved the usefulness of the method.