Table 2 Supramolecular chiroselective “logic gates”
Host
1R
1R
1S
1S
Input
Amine
Guest, N
BR
BS
BR
BS
Output
2
3
4
5
low
high
low
high
high
low
high
low
low
high
low
low
low
Fig. 2 “Logic gate” is a term borrowed from electronics where it
represents an elementary building block of a digital circuit. Most logic
gates have two inputs and one output. At any given moment, every terminal
is in one of the two binary conditions low (0) or high (1), represented by
different voltage levels. Extending the concept to the present systems, the
two inputs are the configuration of the macrocycle M and of the amine
B and the output is either the loss of B (relatively large k-1/k2; high state)
or the loss of nucleoside N (relatively small k-1/k2; low state) from the
[M·H·N·B]+ “logic gates”(Table 1).
low
high
high
to over 20%. Since the normal dynamic range of the FT-ICR is
ca. 103:1, it can be concluded that the pseudo-equilibrium step
involving [1R·H·4]+ (eqn (1)) is ca. 200 times more shifted towards
the reactants (k1/k-1 < 2 ¥ 10-14 cm3 molecule-1 and k-1/k2 >
5 ¥ 103) than that involving [1S·H·4]+ (k1/k-1 = 5 ¥ 10-12 cm3
molecule-1 and k-1/k2 ~ 25). This means that the [1R·H·4]+ complex
is inert towards B, whereas the same amine B can efficiently
add to the [1S·H·4]+ diastereoisomer and displace the nucleoside
from it.
Nazionale delle Ricerche (CNR). Research grant from Fondazione
Roma (Italy) to B.B. is gratefully acknowledged.
References
Thus, the diastereomeric complexes of Table 1 behave as
supramolecular devices which, depending upon the configuration
of both the macrocycle and the amine B, can or cannot release
the nucleoside. In particular, the [1R·H·4]+ and [1S·H·4]+ systems
can be regarded as the first example of gas-phase supramolecular
“logic gate” that, in the presence of a suitable reactant (B), can
selectively release one enantiomer of a chiral guest and keeping
bound the other enantiomer (Fig. 2 and Table 2). This view can be
somewhat extended to the other complexes investigated, although
in this case the adverb “selectively” must be replaced by “preferen-
tially”.
In conclusion, the present gas-phase results provide a first exam-
ple of selective release of biomolecules from chiral supramolecular
systems (bio-”logic gates”). Assessment of the factors governing
the process may be a starting point for understanding controlled
drug delivery from chiral molecular carriers.
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configuration (1R) or in the all-S one (1S), in their cone conformations,
were synthesized and purified according to established procedures
(ref. 5).
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7 For a comprehensive survey on gas-phase chiral recognition see: “Chiral
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8 2¢-Deoxycytidine: 4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymet-
hyl)-tetrahydro-furan -2-yl]-1H-pyrimidin-2-one.
9 Cytidine:
4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymet-
hyl)-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one.
10 Cytarabine: 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymet-
hyl)-tetrahydro-furan-2-yl]-1H-pyrimidin-2-one.
Acknowledgements
11 Gemcitabine:
4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy -5-
hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one.
12 (a) T. Su and W. J. Chesnavitch, J. Chem. Phys., 1982, 76, 5183–5185;
(b) T. Su, J. Chem. Phys., 1988, 88, 4102–41035355–5356.
Work supported by the Ministero dell’Istruzione dell’Universita`
e della Ricerca (MIUR-PRIN-2007H9S8SW) and the Consiglio
This journal is
The Royal Society of Chemistry 2011
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