ISMSC 2007 - Università degli Studi di Pavia

New Amido-Based Multicyclic Hosts for Anions
Sung Ok Kang, Victor W. Day, Kristin Bowman-James
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence KS 66045.
Anions play very important roles in biochemical systems as well as in the environment. Since
anion coordination chemistry has become an intense research area, hosts for anions with
elegant architectures have developed rapidly over several decades.[1] Because anions have
several different distinguishing aspects compared to cations, such as larger size, high solvation
energy, various shapes (spherical, linear, trigonal planar, and tetrahedral), and sometimes pH
dependence, designing anion receptors is even more challenging.[2] In order to achieve the
goal of designing highly selective hosts for anions, both the choice of functional groups as a
hydrogen bonding sites and their arrangements in host frameworks will be crucial.
Even though multicycles have tended to bind anions strongly due to their increased
dimensionality as well as their increased number of binding sites, only a few amido-based
multicyclic hosts for anions have been published to date.[3] These reported hosts include a
bicycle and tricycle based on the prototype 1 reported by our group.[4,5] Recently we modified
the design strategy to obtain two new classes of bicyclic and tricyclic hosts, 2 and 3, the
frameworks of which are also based on monocycle 1.
H 3 C
O
N
H
N
H
N
O
O
X
N
H
A N CH3 H
N
X
O
- A- A- A- 1 X=CHorN
Monocycle
2
Bicycles
3
Tricycles
PSA 83
Each of the new multicyclic hosts displays its own unique structural and chemical binding
properties in terms of anion binding. NMR and crystallographic studies of the new anion hosts
will be described.
[1] A. Bianchi, K. Bowman-James, E. García-España (Eds.), Supramolecular Chemistry of
Anions, WILEY-VCH, New York, 1997.
[2] P. D. Beer, P. A. Gale, Angew. Chem. Int. Ed. 2001, 40, 486-516.
[3] S. O. Kang, M. A. Hossain, K. Bowman-James, Coord. Chem. Rev. 2006, 250, 3038-3052.
[4] S. O. Kang, J. M. Llinares, D. Powell, D. VanderVelde, K. Bowman-James, J. Am. Chem.
Soc. 2003, 125, 10152-10153.
[5] S. O. Kang, D. Powell, V. W. Day, K. Bowman-James, Angew. Chem. Int. Ed. 2006, 45,
1921-1925.
Prodigiosin Analogues and Related Polypyrrolic Anion Receptors;
Thermodynamic and Kinetic Studies
Jonathan L. Sessler † , Elizabeth T. Karnas † , Dustin E. Gross † , Leah R. Eller † , Won-Seob Cho † ,
Sergios Nicolaou † , Apolonio Aguilar † , Jeong Tae Lee † , Vincent M. Lynch † , Darren J. Magda, ‡
Kenneth A. Johnson †
† Univeristy of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA
‡ Pharmacyclics, Inc. 995 East Arques Avenue Sunnyvale, California 94085, USA
The prodigiosin alkaloid is a natural product consisting of a pyrrolylpyrromethene core
and has been shown to have a broad range of biological activity 1 , including pH modulation, cell
cycle inhibition, DNA cleavage, 2 and mitogen-activated protein kinase inhibition. 3 We are most
interested in the role of prodigiosin as a pH modulator, which it accomplishes by H + /Cl - symport
activity. 4,5
Our group has sought to provide chemical evidence for this binding/transport event by
synthesizing a basic series consisting of a ‘natural’ prodigiosin 1, and simple prodigiosin
analogues. 6 Binding constants were determined through isothermal titration calorimetry (ITC),
transport efficiency was determined by efflux across a phospholipid membrane as a function of
time and anticancer activity was tested in vitro with A549 human lung and PC3 human prostate
cancer cells. These studies 6 revealed a correlation between transport efficiency and anticancer
activity, while the binding constants (Ka), a thermodynamic parameter, was not found to be a
predictor of biological activity. This leads us to suggest that kinetic effects, associated with
anion complexation or decomplexation, play a dominant role.
Ongoing detailed analyses, which will be the subject of this presentation, have served to
underscore the fact that prodigiosin analogues 2, as well as several other oligopyrrolic systems,
are characterized by complex thermodynamic and kinetic anion binding interactions that are a
function of not only the structure itself, but also the counter-ion and solvent as well.
N
H
X-
N
H
H +
OMe
N
1 2
[1] Fürstner, A. Angew. Chem. Int. Ed. 2003, 42, 3582-3603.
[2] Melvin, M.; Tomlinson, J.; Saluta, G.; Kucera, G.; Lindquist, N.; Manderviller, R. J. Am.
Chem. Soc. 2000, 122, 6333-6334.
[3] Tomas, R.; Montaner, B.; Llagostera, E.; Soto-Cerrato, V. Biochem. Pharmacol. 2003, 66,
1447-1452.
[4] Sato, T.; Konno, H.; Tanaka, Y.; Kataoka, T.; Nagai, K.; Wasserman, H.; Okhuma, S. J. Bio.
Chem. 1998, 273, 21455-21462.
[5] Seganish, J.; Davis, J. Chem. Commun., 2005, 5781-5783
[6] Sessler, J.; Eller, L.; Cho, W.S.; Nicolau, S.; Aguilar, A.; Lee, J.T.; Lynch, V.; Magda, D.
Angew. Chem. Int. Ed. 2005, 44, 5989-5992.
N
H
N
H
H
N
+ X-
PSA 84