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Building on Cram's legacy: stimulated gating in hemicarcerands.

Liu F, Helgeson RC, Houk KN - Acc. Chem. Res. (2014)

Bottom Line: We found that the side portals of this hemicarceplex have multiple thermally accessible conformations.Gates are built onto host molecules so that the opening or closing of such gates is stimulated by reducing or oxidizing conditions, or by ultraviolet irradiation.The experimental and computational investigations of gated hemicarcerands and several potential applications of gated hemicarceplexes are described in this Account.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.

ABSTRACT
CONSPECTUS: Donald Cram's pioneering Nobel Prize-winning work on host-guest molecules led eventually to his creation of the field of container molecules. Cram defined two types of container molecules: carcerands and hemicarcerands. Host-guest complexes of carcerands, called carceplexes, are formed during their synthesis; once a carceplex is formed, the trapped guest cannot exit without breaking covalent bonds. Cram defined a quantity called constrictive binding, arising from the mechanical force that prevents guest escape. The constrictive binding in carceplexes is high. In contrast, hemicarcerands have low constrictive binding and are able to release the incarcerated guests at elevated temperatures without breaking covalent bonds. We have designed molecules that can switch from carcerand to hemicarcerand through a change in structure that we call gating. The original discovery of gating in container molecules involved our computational studies of a Cram hemicarceplex that was observed to release a guest upon heating. We found that the side portals of this hemicarceplex have multiple thermally accessible conformations. An eight-membered ring that is part of a portal changes from a "chair" to a "boat" structure, leading to the enlargement of the side portal and the release of the guest. This type of gating is analogous to phenomena often observed with peptide loops in enzymes. We refer to this phenomenon as thermally controlled gating. We have also designed and synthesized redox and photochemically controlled gated hemicarceplexes. Gates are built onto host molecules so that the opening or closing of such gates is stimulated by reducing or oxidizing conditions, or by ultraviolet irradiation. In both cases, the appropriate stimuli can produce a carceplex (closed gates) or hemicarceplex (open gates). A hemicarceplex with closed gates behaves like a carceplex, due to its very high constrictive binding energy. When the gates are opened, constrictive binding is dramatically lowered, and guest entrance and exit become facile. This stimulated switching between open and closed states controls access of the guest to the binding site. The experimental and computational investigations of gated hemicarcerands and several potential applications of gated hemicarceplexes are described in this Account.

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Structuresof hosts with large portals (left) and small portals(right); one of the four side portals in each structure is highlightedin blue.
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fig7: Structuresof hosts with large portals (left) and small portals(right); one of the four side portals in each structure is highlightedin blue.

Mentions: From the analysis of gating processes in four different hemicarcerands,we found that the importance of gating in the complexation and decomplexationprocesses varies, depending on the nature of guests and the size ofthe hemicarcerand portals.11 Some hostshave portals so large that the guests readily pass into and out ofthe cavity with almost no barriers. In such cases, gating does notinfluence the entry and exit of guests. An example is the complexationof hemicarcerand 2 (Figure 7,left) with benzene. Calculations with the AMBER* force field showedthat there is no barrier to complexation, and the decomplexation barrieris only about 8 kcal/mol with solvation corrections, which suggestsrapid entry and exit of the benzene without gating. In contrast, somehosts have portals too small to allow the passage of guest moleculeseven with an open gate. The barrier to loss of dimethyl sulfoxidefrom 3b (Figure 7, right) is calculatedto be greater than the energy to break a C–C bond (∼90kcal/mol). Some hosts have portals small enough to incorporate andbind guests, but still big enough for the exit of the guests upona conformational change, as the release of acetonitrile from hemicarcerand 1. Gating becomes a crucial factor in forming stable, andyet reversible, complexes of such hosts with appropriate guests.


Building on Cram's legacy: stimulated gating in hemicarcerands.

Liu F, Helgeson RC, Houk KN - Acc. Chem. Res. (2014)

Structuresof hosts with large portals (left) and small portals(right); one of the four side portals in each structure is highlightedin blue.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215849&req=5

fig7: Structuresof hosts with large portals (left) and small portals(right); one of the four side portals in each structure is highlightedin blue.
Mentions: From the analysis of gating processes in four different hemicarcerands,we found that the importance of gating in the complexation and decomplexationprocesses varies, depending on the nature of guests and the size ofthe hemicarcerand portals.11 Some hostshave portals so large that the guests readily pass into and out ofthe cavity with almost no barriers. In such cases, gating does notinfluence the entry and exit of guests. An example is the complexationof hemicarcerand 2 (Figure 7,left) with benzene. Calculations with the AMBER* force field showedthat there is no barrier to complexation, and the decomplexation barrieris only about 8 kcal/mol with solvation corrections, which suggestsrapid entry and exit of the benzene without gating. In contrast, somehosts have portals too small to allow the passage of guest moleculeseven with an open gate. The barrier to loss of dimethyl sulfoxidefrom 3b (Figure 7, right) is calculatedto be greater than the energy to break a C–C bond (∼90kcal/mol). Some hosts have portals small enough to incorporate andbind guests, but still big enough for the exit of the guests upona conformational change, as the release of acetonitrile from hemicarcerand 1. Gating becomes a crucial factor in forming stable, andyet reversible, complexes of such hosts with appropriate guests.

Bottom Line: We found that the side portals of this hemicarceplex have multiple thermally accessible conformations.Gates are built onto host molecules so that the opening or closing of such gates is stimulated by reducing or oxidizing conditions, or by ultraviolet irradiation.The experimental and computational investigations of gated hemicarcerands and several potential applications of gated hemicarceplexes are described in this Account.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.

ABSTRACT
CONSPECTUS: Donald Cram's pioneering Nobel Prize-winning work on host-guest molecules led eventually to his creation of the field of container molecules. Cram defined two types of container molecules: carcerands and hemicarcerands. Host-guest complexes of carcerands, called carceplexes, are formed during their synthesis; once a carceplex is formed, the trapped guest cannot exit without breaking covalent bonds. Cram defined a quantity called constrictive binding, arising from the mechanical force that prevents guest escape. The constrictive binding in carceplexes is high. In contrast, hemicarcerands have low constrictive binding and are able to release the incarcerated guests at elevated temperatures without breaking covalent bonds. We have designed molecules that can switch from carcerand to hemicarcerand through a change in structure that we call gating. The original discovery of gating in container molecules involved our computational studies of a Cram hemicarceplex that was observed to release a guest upon heating. We found that the side portals of this hemicarceplex have multiple thermally accessible conformations. An eight-membered ring that is part of a portal changes from a "chair" to a "boat" structure, leading to the enlargement of the side portal and the release of the guest. This type of gating is analogous to phenomena often observed with peptide loops in enzymes. We refer to this phenomenon as thermally controlled gating. We have also designed and synthesized redox and photochemically controlled gated hemicarceplexes. Gates are built onto host molecules so that the opening or closing of such gates is stimulated by reducing or oxidizing conditions, or by ultraviolet irradiation. In both cases, the appropriate stimuli can produce a carceplex (closed gates) or hemicarceplex (open gates). A hemicarceplex with closed gates behaves like a carceplex, due to its very high constrictive binding energy. When the gates are opened, constrictive binding is dramatically lowered, and guest entrance and exit become facile. This stimulated switching between open and closed states controls access of the guest to the binding site. The experimental and computational investigations of gated hemicarcerands and several potential applications of gated hemicarceplexes are described in this Account.

Show MeSH
Related in: MedlinePlus