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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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(a) Structure of thermally gated hemicarcerand 1 withone side portal colored in blue, one polar portal colored in red,and one eight-membered ring colored in green and circled (there areeight units of this type in 1). (b) CPK model of 1b showing the polar portal is slightly larger than the sideportals. (c) The CH2-in and CH2-out conformationalchange in an eight membered ring in 1 (the unit thatis circled in part a) that leads to the closing and opening of thethermal gate.
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fig3: (a) Structure of thermally gated hemicarcerand 1 withone side portal colored in blue, one polar portal colored in red,and one eight-membered ring colored in green and circled (there areeight units of this type in 1). (b) CPK model of 1b showing the polar portal is slightly larger than the sideportals. (c) The CH2-in and CH2-out conformationalchange in an eight membered ring in 1 (the unit thatis circled in part a) that leads to the closing and opening of thethermal gate.

Mentions: Thesynthesis of thermally gated hemicarcerands can be achievedby linking two hemispheres by four bridges of proper length.12 The synthesis of host 1a is anexample of this strategy (Figure 3a). Oneof the four side portals of 1a is highlighted in blue,while a polar portal is highlighted in red. This host, 1a, forms complexes with one or two acetonitriles molecules duringits synthesis from a tetrathiolate hemisphere plus a tetrachloro hemispherein acetonitrile solvent. The complex with two acetonitriles losesone guest molecule upon heating at 110 °C for 3 days, but theescape of the second acetonitrile was not observed.13 Based on CPK space-filling models, Cram proposed that theacetonitrile could only escape through the polar portal, since itis larger than the side portal as shown in Figure 3b.


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

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

(a) Structure of thermally gated hemicarcerand 1 withone side portal colored in blue, one polar portal colored in red,and one eight-membered ring colored in green and circled (there areeight units of this type in 1). (b) CPK model of 1b showing the polar portal is slightly larger than the sideportals. (c) The CH2-in and CH2-out conformationalchange in an eight membered ring in 1 (the unit thatis circled in part a) that leads to the closing and opening of thethermal gate.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: (a) Structure of thermally gated hemicarcerand 1 withone side portal colored in blue, one polar portal colored in red,and one eight-membered ring colored in green and circled (there areeight units of this type in 1). (b) CPK model of 1b showing the polar portal is slightly larger than the sideportals. (c) The CH2-in and CH2-out conformationalchange in an eight membered ring in 1 (the unit thatis circled in part a) that leads to the closing and opening of thethermal gate.
Mentions: Thesynthesis of thermally gated hemicarcerands can be achievedby linking two hemispheres by four bridges of proper length.12 The synthesis of host 1a is anexample of this strategy (Figure 3a). Oneof the four side portals of 1a is highlighted in blue,while a polar portal is highlighted in red. This host, 1a, forms complexes with one or two acetonitriles molecules duringits synthesis from a tetrathiolate hemisphere plus a tetrachloro hemispherein acetonitrile solvent. The complex with two acetonitriles losesone guest molecule upon heating at 110 °C for 3 days, but theescape of the second acetonitrile was not observed.13 Based on CPK space-filling models, Cram proposed that theacetonitrile could only escape through the polar portal, since itis larger than the side portal as shown in Figure 3b.

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