Cucurbit[7]uril host-guest complexes of the histamine H2-receptor antagonist ranitidine.
The macrocyclic host cucurbit[7]uril forms very stable complexes with the diprotonated (K(CB[7])(1) = 1.8 x 10(8) dm(3) mol(-1)), monoprotonated (K(CB[7])(2) = 1.0 x 10(7) dm(3) mol(-1)), and neutral (K(CB[7])(3) = 1.2 x 10(3) dm(3) mol(-1)) forms of the histamine H(2)-receptor antagonist ranitidine in aqueous solution. The complexation behaviour was investigated using (1)H NMR and UV-visible spectroscopy as a function of pH and the pK(a) values of the guest were observed to increase (DeltapK(a1) = 1.5 and DeltapK(a2) = 1.6) upon host-guest complex formation. The energy-minimized structures of the host-guest complexes with the cationic guests were determined and provide agreement with the NMR results indicating the location of the CB[7] over the central portion of the guest. The inclusion of the monoprotonated form of ranitidine slows the normally rapid (E)-(Z) exchange process and generates a preference for the (Z) isomer. The formation of the CB[7] host-guest complex greatly increases the thermal stability of ranitidine in acidic aqueous solution at 50 degrees C, but has no effect on its photochemical reactivity.
Wang
Ruibing
R
Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, ON K7L 3N6, Canada.
Macartney
Donal H
DH
D001952:Bridged-Ring Compounds / Q000737:chemistry*; D006635:Histamine H2 Antagonists / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010777:Photochemistry; D011899:Ranitidine / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
D001952:Bridged-Ring Compounds; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D011899:Ranitidine; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils