Selected Research Publications

Three families of tris-pyridyl methanol ligands were synthesized. An analysis of the Zn2+ binding properties of the ligands revealed that both steric and electronic properties of the pyridine substituents, as well as the nature of the group on the tertiary alcohol oxygen, control the thermodynamics and kinetics of complex formation.

Abstract Metal ions are superb at templating the synthesis of small macrocycles that are decorated with Lewis basic sites. However, for the synthesis of larger macrocycles, or the synthesis of macrocycles devoid of an array of Lewis basic sites, metal ions are less useful. Here we demonstrate that resorcinarenes can be used as templates to engender the efficient formation of large crown ethers. A three step process of 1) tethering moieties to the template, 2) linking those moieties, and 3) then cleaving off the template leads to the efficient formation of a family of aromatic crown ethers. If adaptable, this approach will prove useful for the construction of macrocycles that are hard to obtain from a step-wise synthesis.

The synthesis of three different nanoscale molecular hosts is reported. These cavitands each possess a highly preorganized cavity with an open portal (nearly 1 nm wide), by which guests can enter and egress the cavity. Additionally, these hosts are deep-functionalized with a crown of weakly acidic benzal C--H groups which can form a variety of noncovalent interactions with guest molecules residing within the cavity. Thirty-one guests were examined for their propensity to form complexes with the hosts. Guests that possess halogen atoms were the strongest binders, suggesting the formation of polydentate C--H⋅⋅⋅X--R hydrogen bonds with the deep crown of benzal hydrogens. Exchange rates between the free and bound states were noted to be dependent on the size of the guest and the solvent used to study complexation. In general, stronger binding and slower exchange were noted for complexations carried out in DMSO with highly complementary guests. The orientation of each guest within the cavity was determined using either EXSY NMR spectroscopy or 1H NMR shift data. Cumulatively these results showed that the principal factors directing orientation were interactions with the benzal groups and the type of solvent. Van't Hoff analyses of selected complexations were also carried out. As well as revealing that all complexations were entropically unfavorable, these experiments provided support for guest orientation determinations, and gave an estimation that the formation of a C--H⋅⋅⋅I--R hydrogen bond releases between 1 and 1.5 kcal mol−1.
 

Kinetic analysis of the host guest complexation of a large, open molecular basket and a highly complementary adamantoid guest reveals that for these types of systems a dissociative mechanism is in operation. Hence, the resident adamantyl guest must completely vacate the cavity before another guest molecule can move in to replace it. As a result of the rigid nature of the host, the energy barrier to this process is relatively high, about 16 kcal mol−1 at room temperature. Modifying the cavity of the host by dangling either a methyl group or a hydroxyl group from the portal rim alters the thermodynamic binding profile of these hosts. 1H NMR shift data analysis also reveals that these functional groups can adjust the orientation that monosubstituted guests adopt within the cavity. Additionally, 1H NMR studies of the binding of (E)1,4-dibromoadamantane allow the observation of two energetically similar diastereomeric complexes. An examination of this guest binding to the three hosts reveals that the interchange between the isomers is much faster than the entry and egression rates, and that the functional groups at the rim of each cavity influence both the rates of reorientation and the equilibrium relating the isomers.

The syntheses of reduced-symmetry deep-cavity cavitands by two-stage stereoselective bridging with substituted benzal bromides is reported. Conditions for the optimal formation of the trisbridged derivatives were readily established. However, it was not possible to determine conditions which selectively promoted formation of either one of the two bisbridged species, or the monobridged compound, above the other products. A comparison of yields for A/B bisbridged derivatives verses A/C bisbridged derivatives may indicate that the one-pot formation of deep-cavity cavitands occurs primarily through the former species.

A novel family of deep-cavity cavitands is prepared via the first examples of the stereoselective bridging of resorcin- [4]arenes with carbon electrophiles.