cm0006547_si_001.pdf (263.18 kB)
Nanoconstruction of Microspheres and Microcapsules Using Proton-Induced Phase Transitions: Molecular Self-Recognition by Diamide Diacids in Water
journal contribution
posted on 2001-01-10, 00:00 authored by Phanstiel, R. J. Lachicotte, D. Torres, M. Richardson, H. Matsui, H. Schaffer, F. Adar, J. Liu, D. SeconiBis(Nα-amido-l-phenylalanine)-1,1-cyclobutane dicarboxylate (5) was studied by Fourier
transform infrared (FTIR) spectroscopy, variable-temperature NMR (VT-NMR), transmission
electron microscopy, X-ray crystallography, Raman microscopy, and a novel imaging
technique known as “soft” X-ray microscopy (XRM). Diamide diacid 5 was shown to self-associate into solid microspheres during a proton-induced phase transition from the solvated
state to the desolvated assembled state. These diverse techniques allowed for the delineation
of the molecular recognition events involved in the assembly process. X-ray crystallography
revealed that 5 packs in a bundled helical array comprised of two types of intermolecular
hydrogen bonds (i.e., OCO···HN and COOH···OCN). VT-NMR and IR measurements of
5 (1 mM in CDCl3) revealed the small temperature dependence of the amide NH chemical
shift (Δδ/ΔT = −1.1 ppb/K) and the availability of the “free” amide NH of 5 to form
intermolecular hydrogen bonds. Supramolecular rodlike structures were observed during
the aqueous assembly of 5 into microspheres by XRM. Raman microscopy confirmed that
nearly identical bonding patterns are present in the assembled microsphere and the crystal
architecture of 5. Collectively, these observations provide compelling evidence that the
assembly of 5 occurs via crystalline supramolecular intermediates, which are similar in shape
and have complementary bonding motifs for proper self-recognition. Competition experiments
involving varying concentrations of 5 and its microcapsule-forming cyclopropane analogue
3 revealed that molecular fidelity was less important to the microsphere-forming process
than the related capsule-forming process.