I. Host-guest Chemistry of Cucurbiturils and Its Applications II. Synthesis, Characterization and Properties of a Porphyrin-based Organic Cage

DoctorThis thesis describes (1) the thermodynamic and conformational studies of the complexation of cucurbiturils (CBs) with various guest molecules and (2) the design and synthesis of a new porphyrin-based regular hexahedron organic cage via dynamic covalent chemistry (DCC). Our goals include the fundamental understandings of the host-guest chemistry of cucurbiturils and the spontaneous formation of a well-defined discrete organic cage without preorganizers or templates.Chapter 2 of the thesis describes the complexation thermodynamics of a water soluble cucurbit[6]uril (CB[6]) derivative, cyclohexanocucurbit[6]uril (CB*[6]), with various guest molecules. The complexation thermodynamics of CB*[6] with mono-, di- and multiaminoalkanes in pure water has been extensively examined by ITC, which was discussed based on the conformational and structural information obtained from the 1H-NMR and X-ray analysis. Interestingly, the K for spermine was measured to be 3.4 ？ 1012 M-1, which is the highest ever reported for CB[6] or derivatives. The thermodynamics and 129Xe NMR properties associated with its complexation with Xe in water were also investigated by ITC and hyperpolarized 129Xe NMR methods, respectively, which suggests that the host may serve as an effective molecular ？carrier？ for 129Xe NMR-based biosensors.Chapter 3 of the thesis describes the unusual conformations of alkyl chains bound to the molecular hosts, cucurbit[n]uril (CB[n], n=7,8), and their complexation thermodynamics, which were examined by X-ray crystallography and ITC, respectively. Alkyl chains of aliphatic diammonium ions (CmDA2+, m=9-11) in the cavity of CB[7] showed helical, coiled and bent conformations. In particular, helical conformation of alkyl chain, for the first time, was unequivocally characterized in the solid state. An unconventional U-shaped conformation of the alkyl chain along with two positively charged head groups interacting with the same carbonyl-laced portal of CB[8] adopted by C12DA2+ encapsulated in CB[8], similar to that found for bolaamphiphiles embedded in the archaebacteria membrane was also discovered. In addition, the behaviour of a series of alkanes bound to the molecular host CB[8] was systematically studied. CB[8] and alkyltrimethylammonium (CmTA+, (CH3)3N+CmH2m+1, m=6？16), form 1:1 host-guest complexes with a high binding constant (K ~ 106 M-1). The shortest hexyl chain of C6TA+ can be fully encapsulated in an extended conformation inside the CB[8] cavity. However, for the longer aliphatic chains, C8？C16, the long alkyl tails take a U-shaped conformation inside the cavity. These studies demonstrate that alkanes can adopt rather unusual conformations upon complexation with hosts, and shape themselves such a way to maximize the favorable interactions with the hosts and minimize unfavorable interactions with solvents.Chapter 4 of the thesis describes the photo-switchable ？on-off？ host-guest recognition system based on the complex between CB[7] and a cinnamamide derivative. A new cinnamamide derivative (1E), trans-(3-Phenyl-acryloylamino)-acetic acid, was designed and synthesized as a photoresponsive guest molecule. The cinnamamide derivative and CB[7] forms a stable 1:1 host-guest complex. Upon irradiation with UV light at 300 nm for 3 min to the aqueous solution of CB[7]？1E, a conformational change of the cinnamamide derivative from E- (1E) to Z-conformation (1Z) was induced and subsequently the dissociation of the complex were also evidenced by UV-vis and 1H-NMR spectroscopy. The reasons for the dissociation of the complex seem to be due to (1) the conformational change of cinnamamide moiety and (2) the repulsive force between the carboxylic acid group of 1Z and the electron-rich carbonyl groups on the portal of CB[7]. This new photo-switchable ？on-off？ host-guest recognition system can be used in the fabrication of advanced photoresponsive supramolecular systems such as a molecular machine or a gated ion channel.Chapter 5 of the thesis describes the design and synthesis of a new porphyrin-based regular hexahedron organic cage via dynamic covalent chemistry. The addition of six equivalents of tris-1,3,5-(butyloxy)-tris-2,4,6-(aminomethyl)benzene to a solution of three equivalents of tetrakis(p-formylphenyl)prophyrin in chloroform that contained catalytic amounts of trifluoroacetic acid (TFA) gave quantitatively a well-defined discrete organic cage. The cage can be compared with a regular hexahedron, which is one of the five Platonic solids. The six porphyrins and eight triaminomethyl benzenes occupy the square faces and the vertices, respectively, and the imino groups correspond to the twenty four linkers between the six square faces and the eight vertices of the regular hexahedron. The identity of the cage is supported by 1H-, ROESY- and DOSY- NMR spectroscopy and mass spectrometry analyses. The solvodynamic diameter of the cage was calculated to be 3.4 nm by using the Einstein？Stokes equation for diffusion of spherical molecules, which is in good agreement with that of energy-minimized structure. The modeling calculation predicts a cavity diameter of 2 nm with an inner cavity volume of approximately 4200 ？3. The eight openings in the cage are diamond-shaped (~9 ？ 11 ？). Furthermore, treatment of the porphyrin-based organic cage with zinc acetate gave the Zn-matallated cage and it was also characterized by 1H-NMR spectroscopy and mass spectrometry