The effects of reactant ion rotational excitation on the exothermic proton-transfer reactions of HBr(+)((2)Π(1/2)) and DBr(+)((2)Π(1/2)), respectively, with CO(2) were studied in a guided ion beam apparatus. Cross sections are presented for collision energies in the center of mass system E(c.m.) in the range of 0.23 to 1.90 eV. The HBr(+)/DBr(+) ions were prepared in a state-selective manner by resonance enhanced multiphoton ionization. The mean rotational energy was varied from 3.4 to 46.8 meV for HBr(+)((2)Π(1/2)) and from 1.8 to 40.9 meV for DBr(+)((2)Π(1/2)). Both reactions studied are inhibited by collision energy, as expected for exothermic reactions. For all collision energies considered, the cross section decreases with increasing rotational energy of the ion, but the degree of the rotational dependence differs depending on the collision energy. For E(c.m.) = 0.31 eV, the cross sections of the deuteron transfer are significantly larger than those of the proton transfer. For higher E(c.m.) they differ very little. The current results for the exothermic proton transfer are systematically compared to previously published data for the endothermic proton transfer starting from HBr(+)((2)Π(3/2)) [L. Paetow et al., J. Chem. Phys. 132, 174305 (2010)]. Additional new data regarding the latter reaction are presented to further confirm the conclusions. The dependences on rotational excitation found cannot be explained by the corresponding change in the total energy of the system. For both the endothermic and the exothermic reaction, the cross section is maximized for the smallest rotational energy, at least well above the threshold.
Earlier studies have shown that [3,3]-sigmatropic rearrangements of allyl esters are useful for the construction of fluorine-containing carboxylic acid derivatives. This paper describes the synthesis of 3-aryl-pent-4-enoic acid derivatives bearing either a pentafluorosulfanyl (SF) or a trifluoromethyl (CF) substituent in the 2-position by treatment of corresponding SF- or CF-acetates of p-substituted cinnamyl alcohols with triethylamine followed by trimethylsilyl triflate (TMSOTf). This Ireland-Claisen rearrangement delivered approximate 1:1 mixtures of syn/anti diastereoisomers due to tiny differences (<0.5 kcal/mol) both in the energy of (Z)/(E)-isomeric ester enolates and in the alternative Zimmerman-Traxler transition states of model compounds as shown by DFT calculations. Acidic reaction conditions have to be avoided since addition of the reagents in opposite sequence (first TMSOTf then EtN) led to oligomerization of the cinnamyl SF- and CF-acetates. Treatment of the corresponding regioisomeric 1-phenyl-prop-2-en-1-yl acetates under the latter conditions resulted in [1,3]-sigmatropic rearrangement and subsequent oligomerization of the intermediately formed cinnamyl esters. When EtN was added first followed by TMSOTf, no further reaction of the formed ester was detected.
Matrix
metalloproteinases (MMPs) are emerging as pivotal fine-tuners
of cell function in tissue homeostasis and in various pathologies,
in particular inflammation. In vivo monitoring of
the activity of specific MMPs, therefore, provides high potential
for assessing disease progression and tissue function, and manipulation
of MMP activity in tissues and whole organisms may further provide
a mode of controlling pathological processes. We describe here the
synthesis of novel fluorinated and nonfluorinated analogues of a secondary
sulfonamide-based lead structure, compound 2, and test
their efficacy as in vivo inhibitors and tracers
of the gelatinases, MMP-2 and MMP-9. Using a murine neuroinflammatory
model, we show that compound 2 is a highly effective in vivo inhibitor of both MMP-2 and MMP-9 activity with
little or no adverse effects even after long-term daily oral administration.
A fluorescein-labeled derivative compound 17 shows direct
binding to activated gelatinases surrounding inflammatory cuffs in
the neuroinflammation model and to pancreatic β-cells in the
islets of Langerhans, colocalizing with MMP-2 and MMP-9 activity as
detected using in situ zymography techniques. These
results demonstrate that compound 2 derivatives have
potential as in vivo imaging tools and for future
development for specific MMP-2 versus MMP-9 probes. Our chemical modifications
mainly target the residues directed toward the S1′ and S2′
pockets and, thereby, provide new information on the structure–activity
relationships of this inhibitor type.
A series of nucleophiles, including primary and secondary amines, primary alcohols, and thiols, as well as diethyl malonate and nitromethane, were added to different fluorinated Michael acceptors including 2-fluoroalk-1-en-3-ones and 2-
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