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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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Energydefinitions for host–guest complexation by a carcerandor hemicarcerand.
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fig2: Energydefinitions for host–guest complexation by a carcerandor hemicarcerand.

Mentions: Gating in synthetic hosts was first discovered in our labas aresult of computational investigations on Cram’s hemicarcerands.8 Guest molecules encapsulated in the hydrophobiccavities of hemicarcerands can be released withoutbreaking any covalent bonds when the hemicarceplex is heated to ahigher temperature.9 In contrast, carcerands refer to a group of host molecules that formstable complexes with small organic molecules during synthesis; theincarcerated guests cannot escape without breaking covalent bondsin the hosts. The binding properties in such host–guest systemscan be better described by introducing intrinsic binding (the free energy difference between the complex and the free hostand guest) and constrictive binding (the additionalactivation free energy for decomplexation, arising from the physicalbarrier for egress of guest), as shown in Figure 2.10 The constrictive binding freeenergy is also equal to the free energy of activation for binding.This quantity is near zero for an open receptor, known as a cavitand.


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

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

Energydefinitions for host–guest complexation by a carcerandor hemicarcerand.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Energydefinitions for host–guest complexation by a carcerandor hemicarcerand.
Mentions: Gating in synthetic hosts was first discovered in our labas aresult of computational investigations on Cram’s hemicarcerands.8 Guest molecules encapsulated in the hydrophobiccavities of hemicarcerands can be released withoutbreaking any covalent bonds when the hemicarceplex is heated to ahigher temperature.9 In contrast, carcerands refer to a group of host molecules that formstable complexes with small organic molecules during synthesis; theincarcerated guests cannot escape without breaking covalent bondsin the hosts. The binding properties in such host–guest systemscan be better described by introducing intrinsic binding (the free energy difference between the complex and the free hostand guest) and constrictive binding (the additionalactivation free energy for decomplexation, arising from the physicalbarrier for egress of guest), as shown in Figure 2.10 The constrictive binding freeenergy is also equal to the free energy of activation for binding.This quantity is near zero for an open receptor, known as a cavitand.

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