THEORETICAL AND COMPUTATIONAL WORK
1- DNA intercalation of 3a,9a-diazaperylenium
binding molecules regulate mechanisms central to cellular
function, including DNA replication and gene expression. Many
small molecules that mimic or block these processes offer
potential therapeutic agents. Critical to the understanding of the
function of such molecules is the characterization of their
binding modes, which are usually investigated through ensemble
measurements. Understanding how complexation affects both the
structural and mechanical properties of DNA is an important step
towards understanding the functional mechanisms of binding agents,
and may provide a key to more rational drug design.
Many classes of synthetic and naturally occurring low molecular
weight agents are known to interact with DNA through a variety of
distinct mechanisms, including non-covalent (reversible) or
covalent fixation processes.1 However, most drug-based
strategies have exploited the antigen approach, where
double-stranded DNA is targeted directly by a ligand molecule so
as to interfere with template transcription function or
replication processes. Binding mechanisms typically involve either
interaction in the minor or major grooves of the host duplex,
2 or intercalation between stacked base pairs, although
mixed-mode binding is also often evident, biological response is
primarily governed by the effective residence time of a bound
molecule with cytotoxic effects arising from cellular events that
require the unimpeded DNA template.
3a,9a-diazaperylenium dication (DAP) which has been
may find an application as a fluorescent probe or in
analogy to its quinolizinium building block, and as a DNA binder
with possible antileukemic action.
basic idea came from structural similarity of those quinolizinium
salt with our compound and the fact that our target molecule is
flat, which will facilitate this type of
Intercalation of a planar
molecule in the DNA base pairs stack
2-Computing the Redox Potentials of phenothiazine derivatives.
with an N-aminopropyl side chain and various ring
substituents are potent neuroleptics. With their ability to cross
the blood barrier in the brain; their high solubility in aqueous
and nonaqueous solvents, and their relatively low toxicity and
non-genotoxicity, phenothiazines have been in clinical use for
many years to treat mental disorders such as schizophrenia,
paranoia, and psychosis, additionally not only that but they are
used as antimicrobial drugs, and as an anti-oxidant, anti-tumor.
Cyclic voltammetry of both PTZ
(Phenothiazine) and MPTZ (N-methylphenothiazine) show that
both compounds are oxidized reversibly under the specified
conditions. so that the new values are 846 mV for PTZ and 962 mV
for MPTZ (vs. NHE). The redox values reveal something very
appealing; MPTZ is harder to oxidize than PTZ. Although alkylation
is known to increase the electron density and thus render aromatic
systems more easily oxidized.
Semiempirical Austin Model 1
(AM1), ab initio Hartree-Fock (HF) and Density Functional
Methods (DFT) were employed in the geometry optimization and in
the computation of the one-electron oxidation potentials of
phenothiazine and N-methylphenothiazine. The calculations
show that N-methylphenothiazine radical cation is nonplanar
but the phenothiazine radical cation is flat. Using the Continuum
Solvation Module (PCM) for prediction of the solvation energies;
the DFT/ B3PW91/6-311+g* method gave the best agreement with the
experimental redox potential for both compounds.
radical cation (MPTZ+·)
The structures of
Phenothiazine, N-methylphenothiazine and
their radical Cations
A. M. Rawashdeh. “Computing
the Redox Potentials of Phenothiazine and N-methylphenothiazine”
Abhath Alyarmouk “Basic Science and Engineering” 2005, 14(2) 195-208
Doped Aerogels as platforms of gas sensors
compounds shown below were synthesized, characterized in solution
and frozen matrices, and evaluated as dopants of sol-gel
materials. The intramolecular quenching efficiency of 4-benzoyl-N-methylpyridinium
cation in solution depends on the solvent. In frozen matrices or
absorbed on the surfaces of silica aerogel, both Ru(II)
complex/electron acceptor dyads are photoluminescent. The
photoluminescence of our Ru(II) complex dyads adsorbed on aerogel
is quenchable by O2 diffusing through the mesopores.
Thus, in the presence of O2, aerogels doped with dyads
based on 4-benzoyl-N-methylpyridinium can modulate their
photoluminescence over a wider dynamic range than aerogels doped
with dyads based on viologen, and both are more sensitive than
aerogels doped with Ru(II) tris(1,10-phenanthroline). Furthermore,
in contrast to frozen solutions, the luminescent moieties in the
bulk of aerogels kept at low temperatures are still accessible,
leading to more sensitive platforms for oxygen sensors than their
room temperature counterparts.
temperature response of a silica aerogel doped with 1 under
an alternating stream
of N2 and O2. The
fastest switching rate is 15 s; emission was monitored at 643 nm.
in the emission spectra at 77 K of silica aerogels doped with
1 (B) and 2 (C) under nitrogen and under oxygen
N. Leventis; A. M.
Rawashdeh; I. A. Elder; J. Yang; A. Dass; C. Sotiriou-Leventis “Synthesis
of Ru(II) tris(1,10-phenanthroline)- electron acceptors dyads
incorporating the 4-benzoyl-N-methylpyridinium cations or N-benzyl-N´-methylviologen.
Characterization in fluid and frozen solutions, and on silica aerogels”
Chem. Mater. 2004, 16(8), 1493-1506
The effect of substitution on stepwise
Dendrimers are self-repeating globular branched star molecules,
whose fractal structure continues to fascinate, challenge, and
inspire. Functional dendrimers may incorporate redox centers, and
potential applications include antennae molecules for light
harvesting, sensors, mediators, and artificial biomolecules.
e-transfer across the perimeter of dendrimers should depend on
their rigidity, but it is unclear whether it would be more or less
efficient than e-transfer along the branches. As these questions
have important implications for molecular design, they were
investigated with star systems 1-4, serving as
models of first- and second-generation redox dendrimers.
The rigidity of the star 1, provides a complementary view
of the fact that fast e-transfer along the perimeter of
core-branch systems requires flexible branches. From a practical
viewpoint, redox equivalents emerging from the core of a rigid
light-harvesting system would be localized at the tips of the
branches they emerge from core of a rigid light-harvesting system
would be localized at the tips of the branches they emerge from,
creating issues of efficient bimolecular e-transfer to redox
quenchers in their immediate environment. Flexible branches may
not only facilitate e-transfer along the perimeter but may also
fold, rendering internal redox centers more accessible.
J. Yang; A. M.
Rawashdeh; W. Oh; C. Sotiriou-Leventis; N. Leventis “Redox-active
star molecules incorporating the 4 benzoylpyridinium cation:
implications for the charge transfer efficiency along branches vs.
across the perimeter in dendrimers” J. Am. Chem. Soc. 2004,