4th EucheMs chemistry congress

tuesday, 28-Aug 2012 | wednesday, 29-Aug 2012
s604
chem. Listy 106, s587–s1425 (2012)
Analytical chemistry Electrochemistry, Analysis, sample manipulation
life science, clinical and environmental applications
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ChirAL AnALySiS of ACyCLiC nuCLeoSide
PhoSPhonAteS-BASed Anti-AidS druGS By
CAPiLLAry eLeCtroPhoreSiS
v. KASiCKA 1 , v. SoLinovA 1 , P. SAzeLovA 1 ,
h. MiKySKovA 1 , P. JAnSA 2 , M. KreCMerovA 2 ,
A. hoLy 2
1 Institute of Organic Chemistry and Biochemistry AS CR v.v.i.,
Electromigration Methods, Prague 6, Czech Republic
2 Institute of Organic Chemistry and Biochemistry AS CR v.v.i.,
Antimetabolites of Nucleic Acids Components, Prague 6,
Czech Republic
Acyclic nucleoside phosphonates (ANPs) are broadly used
for treatment of virus diseases. [1] Oral prodrug of 9-(R)-[2-
-(phosphonomethoxy)propyl]adenine, (R)-PMPA (tenofovir), was
approved for treatment of AIDS, and 1-[(S)-3-hydroxy-2-
-(phosphonomethoxy)propyl]cytosine, (S)-HPMPC (cidofovir),
is used for treatment of cytomegalovirus retinitis in patients with
AIDS. Enantiomeric purity control of these drugs is necessary
prior to their medical applications. For this purpose, a new
capillary electrophoretic (CE) method was developed for chiral
analysis of these drugs and related ANPs-based antivirals using
native and derivatized α-, β- and γ-cyclodextrins (CDs) as chiral
selectors. The chiral CE analysis was elaborated using R,S-PMPA
as model stereoisomers, for which the chiral selector, its
concentration, and composition and pH of the background
electrolyte (BGE) were selected. [2] The best CE separation of
(R,S)-PMPA enantiomers was obtained in 30 mM sodium
tetraborate BGE adjusted by NaOH to pH 10.0, with the addition
of 20 mg/mL β-CD. Very good separation resolution, 2.18, was
achieved within a short time, 9 min. The developed and/or slightly
modified CE methods were applicable for chiral analysis of some
related ANPs and subsequently they were employed for
enantiopurity control of several batches of 9-(S)-[3-hydroxy-2-
-(phosphonomethoxy)propyl]-2,6-diaminopurine, (S)-HPMPDAP,
and 9-(R)-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine,
(R)-PMPDAP. Using the UV-absorption detection at 206 nm and
254 nm, the concentration detection limits of the analyzed ANPs
were in the submicromolar level. In addition, association
constants of the complexes of ANPs enantiomers with CDs were
determined from the dependence of effective electrophoretic
mobilities of ANPs enantiomers on CDs concentration in the BGE
by the non-linear regression analysis.
Acknowledgement: The work was supported by GACR
(203/08/1428, P206/12/0453), ASCR (Res. Project
AV0Z40550506, RVO 61388963), and MSMT CR (Centre for
New Antivirals and Antineoplastics 1M0508).
references:
1. A. Holy, Antiviral Res. 2006, 71, 248-253.
2. V. Solinova, V. Kasicka, P. Sazelova, A. Holy,
Electrophoresis 2009, 30, 2245-2254.
Keywords: Analytical Methods; Electrophoresis;
Enantioselectivity; Nucleosides; Nucleotides;
spectrometric methods – i
4 th EucheMs chemistry congress
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MeChAniSMS of enerGy diSSiPAtion And
uLtrAfASt PriMAry eventS in PhotoStABLe
SySteMS: h-Bond, exCeSS eLeCtron,
BioLoGiCAL PhotoreCePtorS
h. ABrAMCzyK 1 , B. BrozeK-PLuSKA 1
1 Technical University of Lodz, Chemistry, Lodz, Poland
The fundamental property of biological systems is
photostability. Without photostability no life would be possible.
Molecular structures responsible for harvesting of the solar energy
must be photostable and resistant to photo-induced chemical
changes or must find a way for a recovery. To answer the
questions about the photostability we have to understand
mechanisms of relaxation and energy dissipation upon an optical
excitation. There is a common agreement that such channels are
provided by some special features of the potential energy surfaces
including the conical intersections. The mechanism seems to be
universal both for simple species such as H-bond systems,
solvated electrons, and biologically important photoreceptor
proteins such as bacteriorhodopsin. [1] This paper reviews recent
progress of understanding light-energy collection and dissipation,
with a special emphasis on the role of the vibronic coupling in
H-bonded systems, solvated electrons and light-initiated
biological photoreceptors. We will concentrate on the
spectroscopic methods such as Raman imaging, the time resolved
coherent anti-Stokes Raman spectroscopy (CARS) and the pumpprobe
transient femtosecond absorption spectroscopy. Detailed
understanding the paths of energy dissipation will reveal
mechanisms that mediate light-induced signal transduction as well
as the role of photoreceptors in photostability protection and
reparation mechanisms in living cells. Recently we have obtained
the results on the normal and cancerous human breast tissue by
Raman spectroscopy and Raman imaging. [2] The results
demonstrate that Raman spectroscopy is able to accurately
characterize pathology of tissue and distinguish between normal,
malignant and benign types.
Acknowledgements: The support through the NSC grants:
2940/B/T02/2011/40 and 3845/B/T02/2009/37.
references:
1. H. Abramczyk, Mechanisms of energy dissipation and
ultrafast primary events in photostable systems: H-bond,
excess electron, biological photoreceptors. Vibrational
Spectroscopy, 2012, 58, 1-11
2. H. Abramczyk, B. Brozek-Pluska, J. Surmacki, J.
Jablonska, R. Kordek, Raman ‘optical biopsy’ of human
breast cancer, Prog. Biophys. Mol. Biol. 108(1–2), 74–81
(2012).
Keywords: energy dissipation; H-bonded systems; solvated
electron; bacteriorhodopsin; breast cancer;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc