ISMSC 2007 - Università degli Studi di Pavia

PSA 39
Cucurbit[n]uril as Supramolecular Structures and Drug Delivery Vehicles
Yunjie Zhao a , Linta Chalissery a , Beth Campbell a , Damian Buck a , Gant Collins a and Anthony
Day a
a Chemistry, School of Physical Environmental and Mathematical Sciences, University of New
South Wales @ Australian Defence Force Academy, Canberra, ACT 2600, Australia. Email:
a.day@adfa.edu.au
Supramolecular structures as drug delivery vehicles are of interest as methods to increasing the
efficacy and/or decreasing the toxicity of pharmaceutical applications. Increased efficacy can
potentially be achieved via improved bio-stability, slow release, effective targeting of a drug to
be delivered, and improved solubility. A reduction in toxicity of pharmaceuticals can potentially
be achieved by selective delivery, concentration controls via slow release, and by limiting bioside-reactions.
We have found that cucurbit[n]uril, Q[n], have the potential to achieve some of
the above goals by direct encapsulation of drugs.[1,2] As an ongoing study into drug delivery
and Q[n] utility in this area, we have made a foray into the employment of Q[n] as a component
within micelles to form pockets capable of holding drugs or direct encapsulation of a drug and
the embedding of the association complex within the micelle. In addition, and as an extension
to this approach we have examined the use of Q[n] as an aid to drug delivery where the Q[n]
acts as a spacer to generate cavities within the core of modified dendrimers, as an indirect Q[n]
application.
[1] Mark S. Bali, Damian P. Buck, Andrew J. Coe, Anthony I. Day and J. Grant Collins,
“Cucurbituril binding of trans-[{PtCl(NH3)2(µ-NH2(CH2)8NH2)] 2+ and the effect on the reaction
with cysteine”, J. . Chem. Soc. Dalton 2006, 45,5337-44.
[2] Nial J. Wheate, Damian P. Buck, Anthony I. Day and J. Grant Collins “ Cucurbit[n]uril binding
of platinum anticancer complexes”, J. Chem. Soc. Dalton 2006, (3) 451-455.
PSA 40
Gas phase computational and experimental characterization of a
tetraphosphonate “aquarius” cavitand that carries water and alcohols
Chris Harmon a , Jason Furlow a , Chadin Dejsupa a , Enrico Dalcanale b , and David V. Dearden a
a Department of Chemistry and Biochemistry, C100 Benson Science Building, Brigham Young
University, Provo, Utah 84602-5700 U.S.A.
b Dipartimento di Chimica Organica ed Industriale and INSTM, Università di Parma, Parco Area
delle Scienze 17/A, 43100 Parma, Italy
Whereas supramolecular hosts that bind ammonium or metal ions in the gas phase are
relatively common, hosts for alcohols are rare. We report computational and experimental
characterization of a tetraphosphonate resorcarene host 1 (Figure 1) that selectively binds
water and alcohols in the gas phase, which we believe is the first example of such a system.
CH3 H3C O O CH3 P
P
O
O
O
O
H 3C
O
O
P
H3C O
CH 3
O
O
P
O CH3 Figure 1. The “aquarius”
cavitand 1.
CH 3
Using extensive conformational searching with the MMFF force
field, followed by full geometry optimization at the B3LYP/6-
31G* level of theory, we have computed gas phase structures
and energies for low energy conformers of 1 and its complexes
with H3O + , H3O + •H2O, and various protonated primary and
secondary alcohols. The computed B3LYP/6-31G* binding
energy for H3O + is 430.8 kJ mol –1 . As the length of the alkyl
chain increases for n-alcohols, the binding energy decreases
from about 380 kJ mol –1 for methanol down to about 350 kJ
mol –1 for n-butanol through n-heptanol. The smaller n-alcohols
bind preferentially with the alkyl chain inside the resorcarene
cavity (Figure 2), but as chain length increases this preference
reverses and for n-propanol and longer alkyl groups the chain
points out of the cavity.
These results are consistent with experiments carried out using
Fourier transform ion cyclotron resonance mass spectrometry,
which indicate that under collisional activation the alcohol
complexes dissociate primarily via loss of the hydrocarbon chain
to produce the very stable hydronium complex. Dissociation
thresholds from energy-resolved experiments [1] are also
consistent with the computational results; in particular, the
threshold for loss of water from the H3O + •H2O complex (with a
B3LYP/6-31G* water binding energy of 137.5 kJ mol –1 ) is much
less than that for loss of water from the H3O + complex (computed
water binding energy of 430.8 kJ mol –1 ). All of the complexes we
have examined are labile toward exchange of water or alcohol for
ethanol; we report ethanol exchange rate constants for each of
the complexes. This work is supported by the U.S. National
Science Foundation (NSF CHE 0615964).
Figure 2. B3LYP/6-31G*
computed structure of
the “tail in” complex of
protonated ethanol
(space filling) with 1
(tubes).
[1] Zhang, H.; Ferrell, T. A.; Asplund, M. C.; Dearden, D. V. Int. J. Mass Spectrom. 2007, in
press.