Solvophobically-driven folding of non-biological oligomers and the solid phase synthesis of phenylacetylene oligomers

Sequence-specific phenylacetylene oligomers consisting of functionalized monomers (hexyl benzoate, hexylphenyl ether, benzonitrile, and tert-butylphenyl) are synthesized in gram quantities using solid-phase methods. Growing oligomers are attached to a divinylbenzene cross-linked polystyrene support by the 1-aryl-3-propyl-3-(benzyl-supported) triazene moiety. This linkage is obtained by reaction of arenediazonium tetrafluoroborate salts with a n-propylamino-modified Merrifield resin. The terminal acetylene is protected with a trimethylsilyl group. After deprotection of the resin-bound terminal acetylene, an aryl iodide monomer or an aryl iodide-terminated oligomer is coupled to the supported oligomer using a palladium(0) catalyst. The cycle can be repeated to produce sequence-specific oligomers of varying length and functionality. The resulting oligomers are liberated from the polymer support by cleavage of the 1-aryl-3-propyl-3-(benzyl-supported) triazene group by reaction with iodomethane producing an aryl iodide. Procedures are described, producing oligomers with higher yields and simplified procedures compared to solution-phase methods.; The ordered sequence of monomers in phenylacetylene oligomers can serve as a repeating motif to produce helical structures in solution which posses a tubular cavity. Calculations with modest size oligomers show stable helical conformations with as few as 8 monomer units. Oligomers with triglyme monomethyl ether benzoate functionalized monomers (R = -COO(CH{dollar}{bsol}rm{bsol}sb2CH{bsol}sb2O){bsol}sb3CH{bsol}sb3){dollar} reveal dramatic chain-length-dependent aromatic chemical shifting in CD{dollar}{bsol}sb3{dollar}CN, indicative of aromatic stacking and helical structure. In addition. when chain length reaches 12 monomer units, oligomers begin to strongly aggregate which may be a result of helical oligomers associating like their corresponding macrocycles in a face-to-face parallel fashion. Chain length dependence of UV/Vis and {dollar}{bsol}sp1{dollar}H NMR spectra provide strong evidence of the ordering of monomers and intramolecular aromatic stacking which is consistent with the formation of helical structures. Using UV/Vis absorption at 303 nm as an indication of helical structure, reversible thermal helix-coil transitions were measured in 4/6, {dollar}{bsol}rm CH{bsol}sb3CN/CHCl{bsol}sb3.{dollar} In agreement with the calculations, the octadecamer possesses the largest shift in {dollar}{bsol}rm{bsol}delta{bsol}sb{lcub}A{rcub},{dollar} the best resolved {dollar}{bsol}sp1{dollar}H NMR spectra of the oligomers longer than 12 monomers, and the largest hypochromic shift at 303 nm which is attributed to intramolecular aromatic stacking.