Cycloaddition Reactions of Azomethine Ylides and 1,3-Dienes on the <i>C</i>_2v-Symmetrical Pentakisadduct of C₆₀

The reactivity of the <i>C</i>_2v-symmetric pentakisadduct of C₆₀ with azomethine ylides and conjugated dienes was studied experimentally and computationally. This derivative possesses four [6,6] double bonds, each with unique electrophilicity. The Diels–Alder reaction studied is a regiospecific, kinetically and thermodynamically guided [4 + 2] process producing [5:1]-hexaadducts with an octahedral addition pattern. The kinetically controlled Prato reaction gives a mixture of regioisomeric [5:1]-hexaadducts. The synthesis of geometrically well-defined supramolecular architectures may benefit from these new types of highly functionalized [5:1]-hexaadducts

Demonstration of In Vitro Resurrection of Aged Acetylcholinesterase after Exposure to Organophosphorus Chemical Nerve Agents

After the inhibition of acetylcholinesterase (AChE) by organophosphorus (OP) nerve agents, a dealkylation reaction of the phosphylated serine, referred to as aging, can occur. When aged, known reactivators of OP-inhibited AChE are no longer effective. Realkylation of aged AChE may provide a route to reversing aging. We designed and synthesized a library of quinone methide precursors (QMPs) as proposed realkylators of aged AChE. Our lead compound (<b>C8</b>) from an in vitro screen successfully resurrected 32.7 and 20.4% of the activity of methylphosphonate-aged and isopropyl phosphate-aged electric-eel AChE, respectively, after 4 days. <b>C8</b> displays properties of both resurrection (recovery from the aged to the native state) and reactivation (recovery from the inhibited to the native state). Resurrection of methylphosphonate-aged AChE by <b>C8</b> was significantly pH-dependent, recovering 21% of activity at 4 mM and pH 9 after only 1 day. <b>C8</b> is also effective against isopropyl phosphate-aged human AChE

Demonstration of In Vitro Resurrection of Aged Acetylcholinesterase after Exposure to Organophosphorus Chemical Nerve Agents

After the inhibition of acetylcholinesterase (AChE) by organophosphorus (OP) nerve agents, a dealkylation reaction of the phosphylated serine, referred to as aging, can occur. When aged, known reactivators of OP-inhibited AChE are no longer effective. Realkylation of aged AChE may provide a route to reversing aging. We designed and synthesized a library of quinone methide precursors (QMPs) as proposed realkylators of aged AChE. Our lead compound (<b>C8</b>) from an in vitro screen successfully resurrected 32.7 and 20.4% of the activity of methylphosphonate-aged and isopropyl phosphate-aged electric-eel AChE, respectively, after 4 days. <b>C8</b> displays properties of both resurrection (recovery from the aged to the native state) and reactivation (recovery from the inhibited to the native state). Resurrection of methylphosphonate-aged AChE by <b>C8</b> was significantly pH-dependent, recovering 21% of activity at 4 mM and pH 9 after only 1 day. <b>C8</b> is also effective against isopropyl phosphate-aged human AChE