nitrophenols and hexafluoroisopropanol

The present contribution reports experimental and computational investigations of the interaction between [Cp*Fe(dppe)H] and different proton donors (HA). The focus is on the structure of the proton transfer intermediates and on the potential energy surface of the proton transfer leading to the dihydrogen complex [Cp*Fe(dppe)(H2)]+. With p-nitrophenol (PNP) a UV/Visible study provides evidence of the formation of the ion-pair stabilized by a hydrogen bond between the nonclassical cation [Cp*Fe(dppe)(H2)]+ and the homoconjugated anion ([AHA]-). With trifluoroacetic acid (TFA), the hydrogen-bonded ion pair containing the simple conjugate base (A-) in equilibrium with the free ions is observed by IR spectroscopy when using a deficit of the proton donor. An excess leads to the formation of the homoconjugated anion. The interaction with hexafluoroisopropanol (HFIP) was investigated quantitatively by IR spectroscopy and by 1H and 31P NMR spectroscopy at low temperatures (200-260 K) and by stopped-flow kinetics at about room temperature (288-308 K). The hydrogen bond formation to give [Cp*Fe(dppe)H]HA is characterized by DeltaH degrees =-6.5+/-0.4 kcal mol(-1) and DeltaS degrees = -18.6+/-1.7 cal mol(-1) K(-1). The activation barrier for the proton transfer step, which occurs only upon intervention of a second HFIP molecule, is DeltaH(not equal) = 2.6+/-0.3 kcal mol(-1) and DeltaS(not equal) = -44.5+/-1.1 cal mol(-1) K(-1). The computational investigation (at the DFT/B3 LYP level with inclusion of solvent effects by the polarizable continuum model) reproduces all the qualitative findings, provided the correct number of proton donor molecules are used in the model. The proton transfer process is, however, computed to be less exothermic than observed in the experiment.

Topics: Computer Simulation; Hydrogen Bonding; Iron; Ligands; Models, Molecular; Molecular Structure; Nitrophenols; Organometallic Compounds; Propanols; Protons; Quantum Theory; Sensitivity and Specificity; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Thermodynamics

Sevoflurane [CF3-CH(OCH2F)-CF3] is biotransformed to inorganic fluoride (F-) and hexafluoroisopropanol, which forms a glucuronide conjugate. Although sevoflurane may be used in newborns without fully developed biotransformation activity, studies were performed using liver slices from rat neonates to determine sevoflurane disposition. Sevoflurane was vaporized in sealed roller culture vials to produce a continuous saturating dose (0.5 mM). After incubation, slices and incubation media were sonicated and centrifuged to remove debris. The supernatant fraction was analyzed for F-, hexafluoroisopropanol, and hexafluoroisopropanol-glucuronide conjugate. The metabolism of sevoflurane by liver slices increased proportionately with time with a stoichiometric production (1:1) of hexafluoroisopropanol and F- in all age groups. Only glucuronide conjugates of hexafluoroisopropanol were found. The rate of sevoflurane biotransformation measured as fluoride production was similar among slices prepared from all neonate age groups. Although no hexafluoroisopropanol-glucuronide was generated by slices from 4-, 6-, and 8-day-old neonates, by day 21, 17% of the total hexafluoroisopropanol is glucuronidated. This contrasts with the lower levels of free hexafluoroisopropanol typically seen in adults liver slices, wherein 51% of the hexafluoroisopropanol was glucuronidated. These studies indicate that sevoflurane is equally metabolized to hexafluoroisopropanol and F-, but a deficiency in glucuronosyltransferase occurs in neonates.

Topics: 1-Propanol; Aging; Anesthetics; Animals; Animals, Newborn; Biotransformation; Ethers; Fluorides; Glucuronosyltransferase; In Vitro Techniques; Liver; Methyl Ethers; Nitrophenols; Propanols; Rats; Rats, Sprague-Dawley; Sevoflurane