This proposal deals with chemically synthesized systems known as encapsulation complexes. They involve weakly bound assemblies in which a host structure completely surrounds one or more molecular guests. These systems are formed reversibly and exist on time scales of milliseconds to days, long enough for many types of interactions, and even reactions to take place within them. The encapsulated molecules are temporarily isolated and their behavior is effected accordingly: their motions and reactions are limited to the capsule, and they are protected from reagents inthe exterior solution or in other capsules. These features are relevant to molecular recognition, computational chemistry, low-barrier hydrogen bonds, autocatalysis and the rules governing molecular assembly. They have counterparts in biology: molecules-within-molecules resemble substrates surrounded by enzymes and agonists surrounded by receptors. They are all dynamic systems, largely shielded from solvent, in which motions are limited and interactions like hydrogen bonds may be magnified. The encapsulation complexes can also show nonlinear properties such as autocatalysis that are characteristic of living systems. The encapsulation of peptides and nucleic acid derivatives takes a step toward the use of these systems for drug delivery. We intend to study how the capsules recognize their guests, how the guest molecules get into and out of the capsules, the nature of the space inside the capsules, their transport properties. We also propose to synthesize new and larger capsules, especially those made up of many identical molecular subunits.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Medicinal Chemistry Study Section (MCHA)
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Lograsso, Philip
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Scripps Research Institute
La Jolla
United States
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Hooley, Richard J; Rebek Jr, Julius (2009) Chemistry and catalysis in functional cavitands. Chem Biol 16:255-64
Restorp, Per; Berryman, Orion B; Sather, Aaron C et al. (2009) A synthetic receptor for hydrogen-bonding to fluorines of trifluoroborates. Chem Commun (Camb) :5692-4
Hooley, Richard; Shenoy, Siddhartha; Rebek Jr, Julius (2008) Electronic and Steric Effects in Binding of Deep Cavitands. Org Lett :
Lledo, Agusti; Hooley, Richard J; Rebek Jr, Julius (2008) Recognition of guests by water-stabilized cavitand hosts. Org Lett 10:3669-71
Podkoscielny, Dagmara; Hooley, Richard J; Rebek Jr, Julius et al. (2008) Ferrocene derivatives included in a water-soluble cavitand: are they electroinactive? Org Lett 10:2865-8
Restorp, Per; Rebek Jr, Julius (2008) Reaction of isonitriles with carboxylic acids in a cavitand: observation of elusive isoimide intermediates. J Am Chem Soc 130:11850-1
Barrett, Elizabeth S; Dale, Trevor J; Rebek Jr, Julius (2008) Stability, dynamics, and selectivity in the assembly of hydrogen-bonded hexameric capsules. J Am Chem Soc 130:2344-50
Iwasawa, Tetsuo; Wash, Paul; Gibson, Christoph et al. (2007) Reaction of an Introverted Carboxylic Acid with Carbodiimide. Tetrahedron 63:6506-6511
Ajami, Dariush; Rebek Jr, Julius (2007) Adaptations of guest and host in expanded self-assembled capsules. Proc Natl Acad Sci U S A 104:16000-3
Barrett, Elizabeth S; Dale, Trevor J; Rebek Jr, Julius (2007) Assembly and exchange of resorcinarene capsules monitored by fluorescence resonance energy transfer. J Am Chem Soc 129:3818-9

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