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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) French door cartoon and analogous gating in 1b. (b) Sliding door cartoon and analogous gating in a four o-xylyl bridged hemicarcerand.
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fig6: (a) French door cartoon and analogous gating in 1b. (b) Sliding door cartoon and analogous gating in a four o-xylyl bridged hemicarcerand.

Mentions: The term “gating” was introduced at that timetodescribe this conformational process that controls the entrance andexit of a guest in synthetic host molecules. Two types of gating existin hemicarceplexes, and we named these French door and sliding door.The types of doors that inspire these names are shown in Figure 6. French door gating describes two edge-to-edgedoor openings, and in 1b refers to the sequential flipsof two −OCH2O– moieties that lead to theopening of a portal. The sliding door often involves the conformationalchange of the whole molecular skeleton, resulting in the enlargementof the side portal, without any pronounced outward motion of the doors,as shown schematically at the bottom right of Figure 6.


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

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

(a) French door cartoon and analogous gating in 1b. (b) Sliding door cartoon and analogous gating in a four o-xylyl bridged hemicarcerand.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: (a) French door cartoon and analogous gating in 1b. (b) Sliding door cartoon and analogous gating in a four o-xylyl bridged hemicarcerand.
Mentions: The term “gating” was introduced at that timetodescribe this conformational process that controls the entrance andexit of a guest in synthetic host molecules. Two types of gating existin hemicarceplexes, and we named these French door and sliding door.The types of doors that inspire these names are shown in Figure 6. French door gating describes two edge-to-edgedoor openings, and in 1b refers to the sequential flipsof two −OCH2O– moieties that lead to theopening of a portal. The sliding door often involves the conformationalchange of the whole molecular skeleton, resulting in the enlargementof the side portal, without any pronounced outward motion of the doors,as shown schematically at the bottom right of Figure 6.

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