4th EucheMs chemistry congress

Monday, 27-Aug 2012 | tuesday, 28-Aug 2012
s589
chem. Listy 106, s587–s1425 (2012)
Plenary lectures
Plenary lecture iii
P L - 0 3
direCted evoLution of StereoSeLeCtive
MonooxyGenASeS AS CAtALyStS in orGAniC
CheMiStry
M. t. reetz 1
1 Philipps-University Marburg, Department of Chemistry,
Marburg, Germany
Enzymes have been used as catalysts by organic chemists
for a long time, but this approach to catalysis has suffred from
traditional limitations which include the often observed poor
stereoselectivity, limited substrate scope and/or insufficient
stability. Directed evolution is a protein engineering technique
which provides a means to address and solve these problems. It
involves repeated cycles of gene mutagenesis, expression and
screening (or selection), thereby exerting evolutionary pressure
on the system. Ever since the first report of directed evlution of
enhanced enantioselectivity of a lipase as the catalyst in the
hydrolytic kinetic resolution of a racemic ester, which we
published 15 years ago (Angew. Chem.Int. Ed. Engl. 1997, 36,
2830–2832), this approach to generating catalysts for asymmetric
transformation has been generalized as shown by numerous
contributions from us and many other groups. Since the bottleneck
of directed evolution is the screening of libraries, we have also
focused on the development of more efficient ways to probe
protein sequence space in the quest to generate mutant libraries
of higher quality having an enhanced frequency of hits.
Accordingly, Iterative Saturation Mutagenesis (ISM) has emerged
as a powerful method in directed evolution, especially in the
embodiment of Combinatorial Active-Site Saturation Test
(CAST).
The lecture will focus on the use of ISM/CAST in the
creation of stereoselective mutants of two types of
monooxygenases: 1) Baeyer-Villiger monooxygenases as
catalysts in enantio- and diastereoselective Baeyer-Villiger
reactions, and 2) P450 enzymes as catalysts in regio- and
stereoselective CH-activating oxidative hydroxylation of steroids
and other types of compounds. None of the selective
transformations presented can be achieved by synthetic transition
metal catalysts or organocatalysts, which underscores the
complementarity of the different approaches to asymmetric
catalysis.
references:
Recent review of directed evolution of stereoselective
enzymes in organic chemistry and biotechnology:
M. T. Reetz, Angew. Chem. Int. Ed. 2011, 50, 138-174.
Keywords: asymmetric catalysis; enzymes; oxidation;
Plenary lecture iV
4 th EucheMs chemistry congress
P L - 0 4
SiMuLAtion And ControL of PhotoCheMiStry
v. BonACiC-KouteCKy 1
1 Department of Chemistry, Humboldt-University Berlin, Berlin,
Germany
Fundamental photochemical processes such as internal
conversion, isomerization, electron or proton transfer involve
nonadiabatic dynamics which couple the nuclear and electronic
motion. Development of efficient methods for the simulation of
these processes and for determination of ultrafast spectroscopic
observables in complex systems involving also their environment
will be presented. [1] This will be illustrated by comparison of
simulated and measured time-resolved photoelectron spectra of
furan, allowing to unravel its underlying photodynamics. [2] The
extension to the condensed phase will show how water influences
the photodynamics of indole. [3]
Furthermore, we present control of photodynamics by
including and tailoring laser fields within the recently developed
semiclassical field-induced surface hopping (FISH) method, [4] thus
allowing to enhance or suppress a chosen photochemical process.
In this approach we combine quantum electronic state population
dynamics with classical nuclear dynamics carried out “on the fly”
without precalculation of potential energy surfaces. Our theoretical
approach allows us to explore the controllability of photochemistry
in complex systems and to unravel the mechanisms underlying the
control of molecular processes. We illustrate the scope of the
method by steering the cis-trans isomerization in prototype Schiff
base molecular switches by shaped laser fields. Control of dynamics
in the condensed phase by FISH method will be presented using
designed laser fields that are capable to invoke fluorescence in the
DNA base adenine. [5] We also show that our FISH method can be
used to reveal fundamental dynamical processes responsible for
optimal dynamic discrimination of the two molecular species flavin
mononucleotide (FMN) and riboflavin (RBF), which exhibit almost
identical spectroscopical features. [6] The selective identification of
target molecules in the presence of structurally and
spectroscopically similar background using optimally shaped laser
fields opens prospects for new applications in multiple areas of
science and engineering. As outlook, the application of optimal
discrimination for label-free bioassays that take advantage of the
twofold role of metallic nanoclusters for nanostructuring of ordered
arrays and enhancement of absorption and fluorescence in proteins
will be presented.
references:
1. R. Mitric, J. Petersen, V. Bonacic-Koutecký, “Multistate
Nondadiabatic Dynamics on the fly in Complex Systems and
its Control by Laser Fields”, in Conical Intersections: Theory,
Computation and Experiment, Springer Verlag, 2011.
2. T. Fuji, Y. Suzuki, T. Horio, T. Suzuki, R. Mitric, U.
Werner, V. Bonacic-Koutecký, J. Chem. Phys. 133,
234303 (2010)
3. M. Wohlgemuth, R. Mitric, V. Bonacic-Koutecký,
J. Chem. Phys. 135, 054105 (2011).
4. R. Mitric, J. Petersen. V. Bonacic-Koutecký, Phys. Rev. A,
79, 053416 (2009).
5. J. Petersen, M. Wohlgemuth, B. Sellner, V. Bonacic-
Koutecký, H. Lischka, R. Mitric, Phys. Chem. Chem.
Phys. 14, 4687 (2012).
6. J. Petersen, R. Mitric, V. Bonacic-Koutecký, J. P. Wolf. J.
Roslund, H. Rabitz, Phys. Rev. Lett., 105, 073003 (2010).
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc