Hydrogen-bonding interactions in crown-(thio)urea complexes with anions,chemical warfare agents and simulants

ABSTRACT

Benzocrown ethers incorporating phenyl and nitrophenyl urea and thiourea moieties were synthesised. Both the nitrophenyl urea and thiourea derivative gave a fluoride-specific colorimetric response but only the urea derivative bound the organophosphonate nerve agent simulants dimethyl methylphosphonate (DMMP) and diisopropyl methylphosphonate (DIMP). This suggested an application as sensors for the nerve agents sarin, soman and cyclosarin which release fluoride upon hydrolysis. Although no fluoride-induced response was observed in the UV-visible spectrum, binding to soman was determined by ¹H NMR. DFT computational simulations suggested that the two crowns adopt different conformations in which both can bind fluoride but only the urea derivative can bind DMMP, DIMP and soman. The results show that, for this system, simulant- and soman-binding behaviours are in good agreement.     

Transition‐Metal‐Free Tunable Chemoselective N Functionalization of Indoles with Ynamides

Two unprecedented N functionalizations of indoles with ynamides are described. By varying the electron‐withdrawing group on the ynamide nitrogen atom, either Z‐indolo‐etheneamides or indolo‐amidines can be selectively obtained under the same metal‐free reaction conditions. The scope and synthetic potential of these reactions, as well as some mechanistic insights provided by DFT calculations, are reported.     

Bioluminescent properties of obelin and aequorin with novel coelenterazine analogues

The main analytical use of Ca²⁺-regulated photoproteins from luminous coelenterates is for real-time non-invasive visualization of intracellular calcium concentration ([Ca²⁺]_i) dynamics in cells and whole organisms. A limitation of this approach for in vivo deep tissue imaging is the fact that blue light emitted by the photoprotein is highly absorbed by tissue. Seven novel coelenterazine analogues were synthesized and their effects on the bioluminescent properties of recombinant obelin from Obelia longissima and aequorin from Aequorea victoria were evaluated. Only analogues having electron-donating groups (m-OCH₃ and m-OH) on the C6 phenol moiety or an extended resonance system at the C8 position (1-naphthyl and α-styryl analogues) showed a significant red shift of light emission. Of these, only the α-styryl analogue displayed a sufficiently high light intensity to allow eventual tissue penetration. The possible suitability of this compound for in vivo assays was corroborated by studies with aequorin which allowed the monitoring of [Ca²⁺]_i dynamics in cultured CHO cells and in hippocampal brain slices. Thus, the α-styryl coelenterazine analogue might be potentially useful for non-invasive, in vivo bioluminescence imaging in deep tissues of small animals.