Synthesis and self-assembly processes of monofunctionalized cucurbit[7]uril.
We present a building-block approach toward functionalized CB[7] derivatives by the condensation of methylene-bridged glycoluril hexamer 1 and glycoluril bis(cyclic ethers) 2 and 12. The CB[7] derivatives Me2CB[7] and CyCB[7] are highly soluble in water (264 mM and 181 mM, respectively). As a result of the high intrinsic solubility of Me2CB[7], it is able to solubilize the insoluble benzimidazole drug albendazole. The reaction of hexamer 1 with glycoluril derivative 12, which bears a primary alkyl chloride group, gives CB[7] derivative 18 in 16% isolated yield. Compound 18 reacts with NaN3 to yield azide-substituted CB[7] 19 in 81% yield, which subsequently undergoes click reaction with propargylammonium chloride (21) to yield CB[7] derivative 20 in 95% yield, which bears a covalently attached triazolyl ammonium group along its equator. The results of NMR spectroscopy ((1)H, variable-temperature, and DOSY) and electrospray mass spectrometry establish that 20 undergoes self-assembly to form a cyclic tetrameric assembly (204) in aqueous solution. CB[7] derivatives bearing reactive functional groups (e.g., N3, Cl) are now available for incorporation into more complex functional systems.
Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
Brittany
B
Vinciguerra
Liping
L
Cao
Joe R
JR
Cannon
Peter Y
PY
Zavalij
Catherine
C
Fenselau
Lyle
L
Isaacs
D000480:Alkynes / Q000737:chemistry*; D001562:Benzimidazoles; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D057930:Click Chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D058105:Polymerization; D012995:Solubility; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines
D000480:Alkynes; D001562:Benzimidazoles; D001952:Bridged-Ring Compounds; D007093:Imidazoles; C031000:benzimidazole; C092018:glycoluril; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines