TY - JOUR
T1 - Flexibility Coexists with Shape-Persistence in Cyanostar Macrocycles
AU - Liu, Yun
AU - Singharoy, Abhishek
AU - Mayne, Christopher G.
AU - Sengupta, Arkajyoti
AU - Raghavachari, Krishnan
AU - Schulten, Klaus
AU - Flood, Amar H.
N1 - Funding Information:
A.H.F. and Y.L. acknowledge project support from the NSF (CHE-1412401). A.S., C.G.M., and K.S. acknowledge support from the National Institutes of Health (NIH, 9P41GM104601). A.S. acknowledges a Beckman Postdoctoral Fellowship. K.R. acknowledges support from the NSF (CHE-1266154). DFT calculations were conducted on Indiana University's supercomputer system, Big Red II, which was supported in part by Lilly Endowment, Inc., through its support for the Indiana University Pervasive Technology Institute, and in part by the Indiana METACyt Initiative. The Indiana METACyt Initiative at IU is also supported in part by Lilly Endowment, Inc. A.H.F. and Y.L. thank B. Qiao at Indiana University for a resourceful discussion on processing MD-simulated data. A.H.F. and Y.L. also thank J. R. Dobscha at Indiana University for a discussion on shape persistence in host-guest chemistry.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/4/27
Y1 - 2016/4/27
N2 - Shape-persistent macrocycles are attractive functional targets for synthesis, molecular recognition, and hierarchical self-assembly. Such macrocycles are noncollapsible and geometrically well-defined, and they are traditionally characterized by having repeat units and low conformational flexibility. Here, we find it necessary to refine these ideas in the face of highly flexible yet shape-persistent macrocycles. A molecule is shape-persistent if it has a small change in shape when perturbed by external stimuli (e.g., heat, light, and redox chemistry). In support of this idea, we provide the first examination of the relationships between a macrocycle's shape persistence, its conformational space, and the resulting functions. We do this with a star-shaped macrocycle called cyanostar that is flexible as well as being shape-persistent. We employed molecular dynamics (MD), density functional theory (DFT), and NMR experiments. Considering a thermal bath as a stimulus, we found a single macrocycle has 332 accessible conformers with olefins undergoing rapid interconversion by up-down and in-out motions on short time scales (0.2 ns). These many interconverting conformations classify single cyanostars as flexible. To determine and confirm that cyanostars are shape-persistent, we show that they have a high 87% shape similarity across these conformations. To further test the idea, we use the binding of diglyme to the single macrocycle as guest-induced stimulation. This guest has almost no effect on the conformational space. However, formation of a 2:1 sandwich complex involving two macrocycles enhances rigidity and dramatically shifts the conformer distribution toward perfect bowls. Overall, the present study expands the scope of shape-persistent macrocycles to include flexible macrocycles if, and only if, their conformers have similar shapes.
AB - Shape-persistent macrocycles are attractive functional targets for synthesis, molecular recognition, and hierarchical self-assembly. Such macrocycles are noncollapsible and geometrically well-defined, and they are traditionally characterized by having repeat units and low conformational flexibility. Here, we find it necessary to refine these ideas in the face of highly flexible yet shape-persistent macrocycles. A molecule is shape-persistent if it has a small change in shape when perturbed by external stimuli (e.g., heat, light, and redox chemistry). In support of this idea, we provide the first examination of the relationships between a macrocycle's shape persistence, its conformational space, and the resulting functions. We do this with a star-shaped macrocycle called cyanostar that is flexible as well as being shape-persistent. We employed molecular dynamics (MD), density functional theory (DFT), and NMR experiments. Considering a thermal bath as a stimulus, we found a single macrocycle has 332 accessible conformers with olefins undergoing rapid interconversion by up-down and in-out motions on short time scales (0.2 ns). These many interconverting conformations classify single cyanostars as flexible. To determine and confirm that cyanostars are shape-persistent, we show that they have a high 87% shape similarity across these conformations. To further test the idea, we use the binding of diglyme to the single macrocycle as guest-induced stimulation. This guest has almost no effect on the conformational space. However, formation of a 2:1 sandwich complex involving two macrocycles enhances rigidity and dramatically shifts the conformer distribution toward perfect bowls. Overall, the present study expands the scope of shape-persistent macrocycles to include flexible macrocycles if, and only if, their conformers have similar shapes.
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U2 - 10.1021/jacs.6b00712
DO - 10.1021/jacs.6b00712
M3 - Article
C2 - 27014837
AN - SCOPUS:84964577497
SN - 0002-7863
VL - 138
SP - 4843
EP - 4851
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 14
ER -