4th EucheMs chemistry congress

thursday, 30-Aug 2012
s831
chem. Listy 106, s587–s1425 (2012)
Physical, theoretical and Computational Chemistry
Ultra fast Processes – ii
o - 5 1 2
KinetiC deterMinAtion of the ALKyLAtinG
PotentiAL of vinyL CoMPoundS
i. f. CeSPedeS-CAMACho 1 , J. A. MAnSo 1 , e. CALLe 1 ,
J. CASAdo 1
1 Universidad de Salamanca, Química física, Salamanca, Spain
Humans are exposed to alkylating compounds present in the
environment and also produced endogenously. Many of these
compounds are mutagenic and genotoxic due to their ability to
interact with proteins and DNA [Gates, K. S. Chem. Res. Toxicol.
2009,22, 1747]. The alkylating potential of four vinyl compounds
(VC) was investigated: acrylamide (AM), acrylonitrile (AN),
acrolein (AC) and acrylic acid (AA). As common substrate of
alkylation, 4–(p–nitrobenzyl)pyridine (NBP) -that forms colored
adducts with them- was used. These reactions occur through an
enthalpy-controlled Michael addition mechanism, being
moderately accelerated by electron-withdrawing groups. The
sequence of alkylating potential was as follows:
AN > AM > AA > AC.
The alkylating potentials of the same VC on the nucleosides
guanosine (Guo) and uridine (Urd) were also investigated. A novel
Ultra Fast Liquid Chromatography (UFLC) technique was used
to monitor the alkylation reactions. The following conclusions
were drawn: i) AC presents the higher alkylating potential,
showing reaction over Guo and Urd at cellular pH, which support
its biological importance [Feng, Z. Proc. Natl. Acad. Sci. U.S.A.
2006, 103, 15404]; ii) the alkylation reactions of Urd and Guo by
the UC occur through a Michael addition mechanism;
iii) a correlation between chemical reactivity (alkylation rate
constants and thermodynamic activation parameters) and
mutagenicity was found; iv) The sequence of alkylating potential
with the nucleosides was as follows: AC > AN > AM ~ AA;
v) the coherence between the results obtained with the nucleosides
and NBP allow one to consider NBP-test as a simple biomimetic
assay with predictive character.
Acknowledgement: We thank the Spanish Ministerio de Ciencia
e Innovación and FEDER Funds (CTQ2010-18999). I.F.C.C.
also thanks the Spanish Ministerio de Asuntos Exteriores y
Cooperación (MAEC–AECID) for Ph.D. grant.
Keywords: alkylation; nucleosides; kinetics;
4 th EucheMs chemistry congress
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc