Folie 1

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Systems Chemistry (AND THE ORIGIN OF
LIFE) Günter von Kiedrowski, RUB, Germany
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Systems Chemistry Workshop _at_ ECLT, Oct. 3-4,
2005 Venice International University
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What is Systems Chemistry?

• A conjunction of supramolecular and prebiotic
  chemistry with theoretical
• biology and complex systems research addressing
  problems relating to
• the origins and synthesis of life.
• The bottom-up pendant of systems biology toward
  synthetic biology.
• Searching for a deeper understanding of
  structural and dynamic prerequisites
• leading to self-replication and
  self-reproduction.
• The quest for the coupling of autocatalytic
  systems, the integration of meta-
• bolic, genetic, and membrane-forming subsystems
  into protocellular entities.
• The quest for the roots of Darwinian
  evolvability in chemical systems.
• The quest for chiral-symmetry breaking and
  asymmetric autocatalysis in
• such systems.

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What is Systems Chemistry?

• A conjunction of supramolecular and prebiotic
  chemistry with theoretical
• biology and complex systems research addressing
  problems relating to
• the origins and synthesis of life.
• The bottom-up pendant of systems biology toward
  synthetic biology.
• Searching for a deeper understanding of
  structural and dynamic prerequisites
• leading to self-replication and
  self-reproduction.
• The quest for the coupling of autocatalytic
  systems, the integration of meta-
• bolic, genetic, and membrane-forming subsystems
  into protocellular entities.
• The quest for the roots of Darwinian
  evolvability in chemical systems.
• The quest for chiral-symmetry breaking and
  asymmetric autocatalysis in
• such systems.

5
What is Systems Chemistry?

• A conjunction of supramolecular and prebiotic
  chemistry with theoretical
• biology and complex systems research addressing
  problems relating to
• the origins and synthesis of life.
• The bottom-up pendant of systems biology toward
  synthetic biology.
• Searching for a deeper understanding of
  structural and dynamic prerequisites
• leading to self-replication and
  self-reproduction.
• The quest for the coupling of autocatalytic
  systems, the integration of meta-
• bolic, genetic, and membrane-forming subsystems
  into protocellular entities.
• The quest for the roots of Darwinian
  evolvability in chemical systems.
• The quest for chiral-symmetry breaking and
  asymmetric autocatalysis in
• such systems.

6
What is Systems Chemistry?

• A conjunction of supramolecular and prebiotic
  chemistry with theoretical
• biology and complex systems research addressing
  problems relating to
• the origins and synthesis of life.
• The bottom-up pendant of systems biology toward
  synthetic biology.
• Searching for a deeper understanding of
  structural and dynamic prerequisites
• leading to self-replication and
  self-reproduction.
• The quest for the coupling of autocatalytic
  systems, the integration of meta-
• bolic, genetic, and membrane-forming subsystems
  into protocellular entities.
• The quest for the roots of Darwinian
  evolvability in chemical systems.
• The quest for chiral-symmetry breaking and
  asymmetric autocatalysis in
• such systems.

7
What is Systems Chemistry?

• A conjunction of supramolecular and prebiotic
  chemistry with theoretical
• biology and complex systems research addressing
  problems relating to
• the origins and synthesis of life.
• The bottom-up pendant of systems biology toward
  synthetic biology.
• Searching for a deeper understanding of
  structural and dynamic prerequisites
• leading to self-replication and
  self-reproduction.
• The quest for the coupling of autocatalytic
  systems, the integration of meta-
• bolic, genetic, and membrane-forming subsystems
  into protocellular entities.
• The quest for the roots of Darwinian
  evolvability in chemical systems.
• The quest for chiral-symmetry breaking and
  asymmetric autocatalysis in
• such systems.

8
What is Systems Chemistry?

• A conjunction of supramolecular and prebiotic
  chemistry with theoretical
• biology and complex systems research addressing
  problems relating to
• the origins and synthesis of life.
• The bottom-up pendant of systems biology toward
  synthetic biology.
• Searching for a deeper understanding of
  structural and dynamic prerequisites
• leading to self-replication and
  self-reproduction.
• The quest for the coupling of autocatalytic
  systems, the integration of meta-
• bolic, genetic, and membrane-forming subsystems
  into protocellular entities.
• The quest for the roots of Darwinian
  evolvability in chemical systems.
• The quest for chiral-symmetry breaking and
  asymmetric autocatalysis in
• such systems.

9
What is Systems Chemistry?

• A conjunction of supramolecular and prebiotic
  chemistry with theoretical
• biology and complex systems research addressing
  problems relating to
• the origins and synthesis of life.
• The bottom-up pendant of systems biology toward
  synthetic biology.
• Searching for a deeper understanding of
  structural and dynamic prerequisites
• leading to self-replication and
  self-reproduction.
• The quest for the coupling of autocatalytic
  systems, the integration of meta-
• bolic, genetic, and membrane-forming subsystems
  into protocellular entities.
• The quest for the roots of Darwinian
  evolvability in chemical systems.
• The quest for chiral-symmetry breaking and
  asymmetric autocatalysis in
• such systems.

10
The main objective of the Action is to
investigate autocatalytic reaction sytems within
supramolecular, prebiotic, and other fields of
chemistry and to develop methods for their
integration into dynamic supersystems.
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What is self-replication?
Self-replication autocatalysis information
transfer
Chemical information can be stored
as Constitution the set of covalent bonds
between atoms or
residues (e.g. in DNA- and peptide
sequences). Configuration the 3D-arrangement
of bonds in stereogenic
units giving rise to enantiomers or
diastereomers. Conformation the 3D-arrangement
of bonds in units allowing
internal rotations.
Transfer of chemical information
...means making instead of breaking
bonds, ...means going
from simple to complex, viz. from small
to large molecules, and not vice
versa. ...requires
molecular templating.
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A bit more than 20 years ago
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Basic kinetics of chemical self-replicating
systems
K1 k
K2 A B C ABC
C2 2 C
rds
kb
A B
C Typical is a square root law
rate autocat. rate background rate
ka a b c1/2 kb a b
with ka k K1 (2K2)-1/2 Autocatalytic
efficiency e ka/kb
M-1/2
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• p 2, hyperbolic growth (Soai reaction D.
  Blackmond) Similar to p 1 but
• survival of the last common (impurity)
  instead of survival of the fittest

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Surfaces - The Fall of the Coexistence Paradigm?
G. von Kiedrowski, E. Szathmary, Selection 2000,
1, 173-179. Selection Versus Coexistence of
Parabolic Replicators Spreading on Surfaces.
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Chemical Copying of Connectivity
L.H. Eckardt, K. Naumann, W.M. Pankau, M. Rein,
M. Schweitzer, N. Windhab, GvK, Nature 2002, 420,
286
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Informational self-assembly nanorobotics
A nano-dodecahedron from 20 trisoligos
pUC
1118
20 nm
881
692
calc. 450 bp
501/489
404
331
model
connectivity
experiment 20 tris-oligos (3x15 bases) 1µM each,
110 mM NaCl, 100 mM HEPES/pH7.5, hybridization
protocol 90.50a.0 Jan Zimmermann et al., Angew.
Chem. in press
agarose gel 2.5
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DonT LOOK JUST LISTEN
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The Wang-Sutherland Replicator
A B C A B p C (1
p) C Fit for p 0.8
B. Wang, I. O. Sutherland, Chem. Comm. 1997,
1495-1496.
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Kindermann's variant
M. Kindermann, I. Stahl, M. Reimold, M. Pankau,
GvK, Angew. Chem. Int. Ed. 2005, 44, 6750-5
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A tool for the systems chemistry toolbox NMR
shift shifting phenomena and how to read them by
kinetic NMR titration
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Shift-shifting observed in the Soai Reaction
M. Pankau, April 2007
M. Pankau, April 2007
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Fundamentals of Kinetic NMR Titrations
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Heisenbergs uncertainity principle DE Dt gt
(2p)-1 h or Dn Dt gt (2p)-1 means to the NMR
time scale Dd n0 Dt gt (2p)-1 In words It is
not possible to observe a discrete signal for a
complex AB if kAB?AB gtgt Dd n0 Example Dd
0.1 ppm, n0 600 MHz Rapid exchange leading to
shift shifting occurs if kAB?AB gtgt 60 s-1
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Classical NMR titration as a means to extract
thermodynamic information from shift changes

• Procedure
• Vary A/B
• Measure Dd
• Fit data to expression
• Get Kd
• Repeat at various T
• Get DH, DS from ln(Kd) vs. 1/T

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Kinetic NMR titration as a means to extract
thermodynamic and kinetic information
by simultaneous SimFitting of integral and shift
changes
di chemical shift of a given proton in pure
species i
dobs observable shift _at_ time t
gi(t) mole fraction of reaction species i _at_
time t
Example Consider a minimal SR system involving
molecules A freely, in AB, in AC, and in ABC
a(t) cA(t) cAB(t) cAC(t) cABC(t). Then
gA(t) cA(t)/a(t), gAB(t) cAB(t)/a(t)
etc dobs(t) gA(t)dA gAB(t)dAB gAC(t)dAC
gABC(t)dABC
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Kinetic NMR titration links structural and
colligative information
di chemical shift of a given proton in pure
species i is structural information derived from
SimFitting can be also computed by QM
methods (Kutzelnigg)
dobs observable shift _at_ time t
gi(t) mole fraction of reaction species i _at_
time t is colligative information
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Temperature dependent kinetics SimFit analysis
based on a full reaction model employing kinetic
titration
A B C
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Kinetic NMR titration _at_ different temperatures
allow an easy construction of experimental energy
profiles
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Life from the view of a chemist Information-pro
cessing autocatalysis capable of changing its own
energy profile (given in Ingemar Ernbergs
lecture series What is life? at Karolinska a
year ago)
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B3LYP/6-31G kcal/mol
Conf. NNN
NNX NXN
NXX TS
0.00 1.73
1.54
3.33 products 0.35
0.00
1.12 0.88 Note Exo TS
are gt 3.48 kcal/mol above lowest energy conf.
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B3LYP/ 6-31G
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What do the experiments say?

• NNXR-NNXS was predicted ...
• ...and found by X-ray as the most stable template
  duplex

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What do the experiments say?

• No strong discrimination between homochiral
  autocatalysis and heterochiral cross-catalysis
  was predicted ...
• ...and found in experiments, in which template
  formation from(R) - and (S)-diene was followed
  in the presence of (R) -template.

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• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

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A most seminal discovery at the start of COST
Systems Chemistry M. Mauksch, S. B. Tsogoeva,
S.-W. Wei, I. M. Martynova. Demonstration of
Spontaneous Chiral Symmetry Breaking in
Asymmetric Mannich and Aldol Reactions.
Chirality, 2007, 19, 816-825.
Wenn das stimmt, fresse ich einen Besenstiel M
. Pankau, OC I, RUB, October 2007
D. Kramer, OC I, RUB, Dec. 2007
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slow
Currently just a work hypothesis
fast
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Pulse Ignition Flow Feedback (PIFF)
Or molecular heartbeat? chemplumber pulse gun?
chemical laser? continuous serial transfer
machine?
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Insight Flow Feedback replaces the need for
higher order autocatalysis or Lottka-
Volterra dynamics for oscillatory
outcome
Brusselator (I. Prigogine) Lottka-Volterra
A ? X A X ? 2
X 2 X Y ? 3 X X Y ? 2
Y B X ? Y C Y ? B
X ? D Overall
Overall A B ? C D
A ? B
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Question Was the early earth
(A) the cup for the prebiotic soup or
(B) a gigantic flow network with lots
of inhomogenieties, gradients
and flow feedback loops?
To (A) Stick to believe in prebiotic
robustness To (B) Start to search for
autocatalysis in lots of organic and
inorganic reactions and bring
them together to talk to each other in a flow
feedback context. Convince politics to
invest in BBB (big bang of biology). BBB
has the same problem size as BB
(LHC_at_CERN). It may lead to a future chemical
industry harvesting reaction networks
discovered in olife research.
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THANKS!
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The nanoconstruction team Lars Henning Eckardt
(CCC, Tet) Wolf-Matthias Pankau (RubiGold) Sven
Mönninghof (Gold chemistry) Jan Zimmermann
(Dodeka) Johanna Stankiewicz (PNA Peptides) Jan
Castaguay (Trisoligo-variants) Stefanie Schorr
(SS-Tet) The replicator team Mike Kindermann
(G1-WS) Insa Stahl (Kin. Tit.) Arne Dieckmann
(Fulvene approach) Sven Plöger (F-PNA kin.
Tit.) Fruitful exchange and next
adjacent Eors Szathmary (Budapest) John
McCaskill (St. Augustin)
Help appreciated Karen Verbist, Antwerp
(TEM) Harald Fuchs, Münster (AFM, STM) Günter
Schmid, Essen (Au55(PPh3)12Cl6) Norbert Sewald,
Bielefeld (SPR) Our industry partners NOXXON,
Berlin, and its former CEO Jens-Peter Fürste
(eSPREAD) NANOGEN Recognomics, Frankfurt, especial
ly Norbert Windhab Markus Schweitzer
(CCC) INFORMIUM, Cologne, with Wolfgang Banzhaf,
Dortmund (sequence design) BAYER Leverkusen
(DE-RUBiGold) Last not least () DFG
SFB-452, BMBF (nanobio nano molecular
medicine) EU PACE (IST/FET) COST D27 FCI, RUB,
GSCB, and others.
Thanks to all....
E-mail kiedro_at_rub.de
Phone [phone] Fax
49(0)234-321-4355 We are a member of RUB's
Graduate School of Chemistry and Biochemistry
www.ruhr-uni-bochum.de/gscb
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DONT LISTEN JUST LOOK
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The main objective of the Action is to
investigate autocatalytic reaction sytems within
supramolecular, prebiotic, and other fields of
chemistry and to develop methods for their
integration into dynamic supersystems.
67
The main objective of the Action is to
investigate autocatalytic reaction sytems within
supramolecular, prebiotic, and other fields of
chemistry and to develop methods for their
integration into dynamic supersystems.
68
The main objective of the Action is to
investigate autocatalytic reaction sytems within
supramolecular, prebiotic, and other fields of
chemistry and to develop methods for their
integration into dynamic supersystems.
69

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

70

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

71

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

72

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

73

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

74

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

75

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

76

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

77

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

78

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

79

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

80

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

81

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

82

• The main objective of the Action is to
  investigate
• autocatalytic reaction sytems within
  supramolecular,
• prebiotic, and other fields of chemistry and to
  develop
• methods for their integration into dynamic
  supersystems.
• genetic
• metabolic
• confined
• asymmetric

Chiral symmetry breaking by nucleation-growth
processes in supramolecular systems From gels to
crystals
b
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The main objective of the Action is to
investigate autocatalytic reaction sytems within
supramolecular, prebiotic, and other fields of
chemistry and to develop methods for their
integration into dynamic supersystems.
84
The main objective of the Action is to
investigate autocatalytic reaction sytems within
supramolecular, prebiotic, and other fields of
chemistry and to develop methods for their
integration into dynamic supersystems.
85
The main objective of the Action is to
investigate autocatalytic reaction sytems within
supramolecular, prebiotic, and other fields of
chemistry and to develop methods for their
integration into dynamic supersystems.
86

Action Structure, Organization Timetable

• MC elected Steering Group with chair, vice, WG
  heads, STSM manager, dissemination manager, ESR
  speaker
• STSMs as dedicated instruments for ESR-based
  knowledge transfer
• Gender issue balance at the level of ESR exchange
  

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THANKS!
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