Complexes of the form
[Os(NH3)5(L)](OTf)2
(where L = an unactivated arene or polyaromatic
hydrocarbon)
are readily protonated by triflic acid (HOTf) to generate stable
arenium, naphthalenium, and anthracenium cations.
A series of substituted anisole complexes were also investigated.
The metal stabilizes the hydrocarbon arenium
system, in most cases, by coordinating the organic ligand in an
η3 fashion. Where L = m-xylene,
however, NMR
data strongly suggest that the arenium ion is essentially
dihapto-coordinated, where an allyl cation fragment
remains
uncoordinated. For the corresponding anisolium systems, NMR data
indicate η2-coordination. It is likely that
η2
and η3 geometries represent limiting cases for a
continuum of distorted allyl (pseudo-allyl) complexes. The
pK
a
values determined for these complexes are dramatically higher than
those of the free arenium cations.
Over
50 years ago, the toxicity of irreversible organophosphate
inhibitors targeting human acetylcholinesterase (hAChE) was observed
to be stereospecific. The therapeutic reversal of hAChE inhibition
by reactivators has also been shown to depend on the stereochemistry
of the inhibitor. To gain clarity on the mechanism of stereospecific
inhibition, the X-ray crystallographic structures of hAChE inhibited
by a racemic mixture of VX (P
R/S
) and
its enantiomers were obtained. Beyond identifying hAChE structural
features that lend themselves to stereospecific inhibition, structures
of the reactivator HI-6 bound to hAChE inhibited by VX enantiomers
of varying toxicity, or in its uninhibited state, were obtained. Comparison
of hAChE in these pre-reactivation and post-reactivation states along
with enzymatic data reveals the potential influence of unproductive
reactivator poses on the efficacy of these types of therapeutics.
The recognition of structural features related to hAChE’s stereospecificity
toward VX shed light on the molecular influences of toxicity and their
effect on reactivators. In addition to providing a better understanding
of the innate issues with current reactivators, an avenue for improvement
of reactivators is envisioned.
BF 3 -mediated additions of lithium phenylacetylide (PhCCLi) to the N-(n-butyl)imine of cyclohexane carboxaldehyde were investigated. IR spectroscopic investigations reveal dramatic aging effects on the addition rates. 6 Li, 11 B, and 13 C NMR spectroscopic studies correlate the loss in reactivity with the condensation of PhCCLi and BF 3 and the consequent formation of a complex mixture of PhCCLi-BF 3 adducts. Employing BF 3 ‚R 3 N complexes eliminates the aging effects by retarding the formation of borates. Kinetic studies implicate a mechanism in which rate-limiting associative substitution of n-Bu 3 N on the BF 3 by the imine is followed by a rapid 1,2-addition of PhCCLi. BF 3 ‚R 3 N complexes are potentially useful substitutes for BF 3 ‚Et 2 O.
The 1,2-addition of lithium phenylacetylide (PhCCLi) to quinazolinones was investigated using a combination of structural and rate studies. (6)Li, (13)C, and (19)F NMR spectroscopies show that deprotonation of quinazolinones and phenylacetylene in THF/pentane solutions with lithium hexamethyldisilazide affords a mixture of lithium quinazolinide/PhCCLi mixed dimer and mixed tetramer along with PhCCLi dimer. Although the mixed tetramer dominates at high mixed aggregate concentrations and low temperatures used for the structural studies, the mixed dimer is the dominant form at the low total mixed aggregate concentrations, high THF concentrations, and ambient temperatures used to investigate the 1,2-addition. Monitoring the reaction rates using (19)F NMR spectroscopy revealed a first-order dependence on mixed dimer, a zeroth-order dependence on THF, and a half-order dependence on the PhCCLi concentration. The rate law is consistent with the addition of a disolvated PhCCLi monomer to the mixed dimer. Investigation of the 1,2-addition of PhCCLi to an O-protected quinazolinone implicates reaction via trisolvated PhCCLi monomers.
The hydrolysis of 2-chloroethyl ethyl sulfide has been examined in an effort to better understand its mechanism under more concentrated conditions. Two salts formed during hydrolysis were synthesized, and an emphasis was placed on determining their effect on the reaction as it proceeded. Unexpected changes in mechanism were seen when excess chloride was added to the reaction. By measuring rates and product distributions as the products were added back into the hydrolysis, a mechanism was developed. The formation of these sulfonium salts represents additional products in the disappearance of 2-chloroethyl ethyl sulfide with k3 in particular causing a deviation away from expected first-order behavior. Sulfonium salts 3 and 4 do not appear to interconvert, and the system as a whole had fewer pathways available than previously proposed. Initial conditions for studying the hydrolysis were very important and could lead to different conclusions depending on the conditions used. This work will aid in better understanding the hydrolysis of the very toxic chemical warfare agent mustard (bis(2-chloroethyl)sulfide) in the environment and during its decontamination.
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