4th EucheMs chemistry congress

Poster Session 2
s1244
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - Nanochemistry, Nanotechnology
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hiGh-LeveL GeoMetriC ControL of new
rotAMeriC MoLeCuLAr CLiP reCePtorS: nMr
StudieS of rotAMer interConverSion And
BindinG to dihydroxyBenzene GueStS
B. MurrAy 1 , B. CreAven 1 , M. Kozien 1 , J. MorAn 1 ,
z. yeASMin 1
1 Institute of Technology Tallaght, Science, Dublin 24, Ireland
Molecular clips, originally introduced by Nolte [1] , are
well-known artificial receptors for dihydroxyaromatics, e.g.
resorcinol, catechol, catecholamines, and other biomolecules
bearing a dihydroxyaromatic unit. Two xylylene walls and two
carbonyl groups, making a pre-organized cavity, are the key
features which bind the substrate via two aryl-stacking & two
hydrogen-bonding interactions. [1]
We have prepared new clips which exist as rotamers:
isomers interconverted by rotation about a single bond. [2] The
rotameric site is incorporated into two phenyl substituents which
control the convergent conformation of the receptor, but do not
directly disturb the binding site.
VT-NMR allows us to interconvert these rotamers, and
measure the energy barrier; the latter is also accessible via free
energy calculations. Surprisingly, the energy barrier was found to
be independent of the nature of the substituent in the
3,3'-positions, but this has now allowed us rationalize the
mechanism of interconversion.
We have now moved on to a more hindered
2,2'-disubstituted series, where variation of the substituent now
allows a significant biasing towards the trans-rotamer being more
stable (up to 100%), and also leads to higher interconversion
barriers.
NMR titration yields binding constants to guests such as
resorcinol.
The new rotameric clips show considerable promise for
high-level control of receptor geometry and of associated binding
of guests to each rotamer.
references:
1. a) Sijbesma, R. P.; Wijmenga, S. S.; Nolte, R. J. M. J. Am.
Chem. Soc. 1992, 114, 9807;
b) Sijbesma, R. P.; Bosman, W. P.; Nolte, R. J. M. J. Org.
Chem. 1991, 56, 3199;
c) Smeets, J. W. H.; van Dalen, L.; Kaats-Richter,
V. E. M.; Nolte, R. J. M. J. Org. Chem. 1990, 55, 454.
2. Kozien, M. PhD Thesis, ITT Dublin, 2009.
Keywords: Molecular recognition; NMR spectroscopy;
Isomerization; Atropisomerism; Host-guest systems;
4 th EucheMs chemistry congress
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nAnoPArtiCuLAte AeroSoL MAnufACturinG
ProCeSS
f. nALBAntoGLu 1 , M. ozBeK 2 , e. er 2 , o. KArBAn 2 ,
G. KAynAr 2 , M. KArABuLut 2 , t. ozden 1
1 Gazi University Faculty of Pharmacy, Pharmaceutical
Chemistry, Ankara, Turkey
2 World Medicine pharmaceuticals, R&D, Istanbul, Turkey
Micronised drug particles for MDI products of aerosol
asthma drugs on the market tends to be acculumated on the inner
surface of containers, or valve components during their shelf lifes.
These micronised particles can also undergo moisture initiated
instability where water can promote chemical instability and
particle adhesion/cohesion differences in these formulations.
While we were devoloping a new aerosol formulation,
suprisingly, we founded that if the formulation have specific
parameters in terms of particles size distribution rate or
morphology which affects obtainable surface area and moisture
absorbtion profiles, the resulted formulation have greater
suspension stability in its life-time use while comparing its former
specifications.
The formulation must be a nanoparticulate pharmaceutical
composition -solid concentration between 0.1 % – 0.5 %- at least
one active pharmaceutical ingredient or salt or solvate, at least
one propellant or propellant mixture, at least one polymer or
polymer combination which has moleculer weight of
190-70000 g/mol.
Formulation trials have been done for these nanoparticulate
aerosol formulations in order to obtain desired particle size and
morphology which are < 0.5 μm and spherical, respectively.
Sample concentrations were used in 2.5 % – 5 % (as weight basis).
Solution or suspension were prepared in water and mixed by
mechanical mixer before spraying through the nozzles. Nano
spray-drying method encapsulates successfully active ingredient
with polymer/ polymer combinations which increases the
moisture and gas barrier properties while increasing surface area
of dispersed particles in liquefied gas. This leads to improvements
on the chemical instability resulted from the moisture in the
structure and more cohesive forces which enhances the uniformity
of the composition. Active ingredient were mixed with polymer
or polymer combinations in different ratios. A yield of 70-75% is
attained with the use of spheric particles with the size between
0,6 and 4 micron.
Keywords: nanoparticles; Drug delivery; Polymers;
Nanotechnology;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc