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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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Top:synthesis of hemicarcerands 6a and its the reversiblegate-closing and gate-opening. The photochemical gates are coloredin green. Bottom: computed structures of complexes formed between para-dimethoxybenzene and 6b.
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fig12: Top:synthesis of hemicarcerands 6a and its the reversiblegate-closing and gate-opening. The photochemical gates are coloredin green. Bottom: computed structures of complexes formed between para-dimethoxybenzene and 6b.

Mentions: While this demonstrates the photochemical gate-opening thatconvertsa carceplex into a hemicarceplex, we undertook the synthesis and studyof a reversibly gated hemicarcerand. We designed a photoswitchablegated hemicarcerand 6a (Figure 12) based on the reversible dimerization of anthracene upon irradiation.29 The dimerization of anthracene is known to occurupon irradiation at relative long wavelength, while the retro-cycloadditionoccurs at the shorter wavelength of 254 nm.30 The synthesis of 6a was achieved by treating the diolwith 9-chloromethylanthracene in DMF using cesium carbonate as thebase (Figure 12). Dimerization of anthraceneoccurs upon irradiation at 350 nm, resulting in the gate closing.Irradiation at 254 nm causes the gate to open and regenerate the bis-anthracene.The reversibility of gate-opening and closing processes of the hemicarcerand 6a was confirmed by 1H NMR and 13C NMRspectra, as well as fluorescence spectroscopy. During one cycle ofalternate irradiation at 350 and 254 nm, the emission band of anthracenedecreases in intensity and then recovers to 99% of the original level.Good reversibility was observed from successive photochemical cycles.


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

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

Top:synthesis of hemicarcerands 6a and its the reversiblegate-closing and gate-opening. The photochemical gates are coloredin green. Bottom: computed structures of complexes formed between para-dimethoxybenzene and 6b.
© Copyright Policy
Related In: Results  -  Collection

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

fig12: Top:synthesis of hemicarcerands 6a and its the reversiblegate-closing and gate-opening. The photochemical gates are coloredin green. Bottom: computed structures of complexes formed between para-dimethoxybenzene and 6b.
Mentions: While this demonstrates the photochemical gate-opening thatconvertsa carceplex into a hemicarceplex, we undertook the synthesis and studyof a reversibly gated hemicarcerand. We designed a photoswitchablegated hemicarcerand 6a (Figure 12) based on the reversible dimerization of anthracene upon irradiation.29 The dimerization of anthracene is known to occurupon irradiation at relative long wavelength, while the retro-cycloadditionoccurs at the shorter wavelength of 254 nm.30 The synthesis of 6a was achieved by treating the diolwith 9-chloromethylanthracene in DMF using cesium carbonate as thebase (Figure 12). Dimerization of anthraceneoccurs upon irradiation at 350 nm, resulting in the gate closing.Irradiation at 254 nm causes the gate to open and regenerate the bis-anthracene.The reversibility of gate-opening and closing processes of the hemicarcerand 6a was confirmed by 1H NMR and 13C NMRspectra, as well as fluorescence spectroscopy. During one cycle ofalternate irradiation at 350 and 254 nm, the emission band of anthracenedecreases in intensity and then recovers to 99% of the original level.Good reversibility was observed from successive photochemical cycles.

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