A.I.

Konovalov

Supramolecular Systems Are

The Bridge From The Inanimate
To Living Matter
3th Internationl Summer School «Supramolecular
Systems in Chemistry and Biology»

6-10 September 2010, Lviv, Ukraine

1
 Big History

Универсальная история

Big Our
Bang Time
Pre-biological Biological Social
Evolution Evolution Evolution

2
 J.-M. Lehn 1978 г.

Supramolecular chemistry may be defined

as “chemistry beyond the molecule”,
bearing on the organized entities of higher
complexity that are resulted from the
association of two or more chemical
species held together by intermolecular
forces.

Supramolecular systems are the selforganized entities that are resulted from
the association of two or more molecules held together by intermolecular
forces(noncovalent bonds).

3
 Nature of the intermolecular forces

Covalent bond 200-300 kJ/mol

Ion-ion interaction

Ion-dipole interaction 50-200 kJ/mol

Dipole-dipole interaction 5-50 kJ/mol

Hydrogen bond 4-120 kJ/mol

Cation –n(π) interaction 5-80 kJ/mol

π-π interaction 0-50 kJ/mol

Van-der-Waals interaction (<5 kJ/mol)

Hydrophobic effects Entropy

4
 The hierarchy of structural organization of matter

Atoms a b c

Molecules A(a-a) B(a-b) C(b-c)

covalent bonds

Supramolecular A ….. A A …… B Supermolecules

systems A ……B ….. C Supramolecular

C ….. A assemblies
non-covalent bonds
(intermolecular)

Biological Community of mutually dependent functionally different

systems supramolecular systems

5
Two approaches will be used in this lecture

1) architecture-functional comparison of synthetic

and natural supramolecular systems

2) energetic analyses of levels of the hierarchy of

structural organization of matter

6
 TWO WAYS IN STUDY OF
SUPRAMOLECULAR SYSTEMS

1 – SYNTHETIC SUPRAMOLECULAR SYSTEMS

Investigation of supramolecular systems
of different architectures with different functions created
on the base of synthetic components

2 – NATURAL SUPRAMOLECULAR SYSTEMS

Investigation of architectures and functions of
supramolecular
systems and their components separated from biological
objects

7
Ch.J.Pedersen Cation Receptors
1967

O O

K+
O O

Dibenzo-18-crown-6
yield 0.4%

8
 Cation receptors
CH3
O

O O O
CH3
+
K

O O

K = 106
CH3
18-crown-6
К+ O
CH3
O

O O К – insignificantly small !
Me
+
K
Me
O O Macrocyclic effect
O
Preorganization

K = 102 Multipoints binding

podand Cooperativety
9
 O
O O
O O

K+ N K+ N J.-M.Lehn
O O
O O 1969
O O
O

K = 106 K = 1010
Macrobicyclic effect
Logarithms of the binding constants

O O O
O O O
O O

Binding
N
selectivity
O
N N
N N N

d ion O
O O O O O

1.36 Ǻ LiMolecular
+
7,5 recognition
4,0 2,0
1.90 Ǻ NaMolecular
+
6,0 9,0
informatics 7,0
2.66 Ǻ K+ 2,0 6,5 10,0 10
Recognition of s-, p- and d-metal cations I.S.Antipin,
I.I.Stoikov
A.I.Konovalov
2007

100,00
90,00
80,00
S S S S 70,00
O O O

Е%
O 60,00
C O 50,00
O C O C O C
R 40,00
R R R
30,00
R: 20,00
c5
O CH CH3 10,00 c3
1 2 0,00
c1
b4
2 CH2 b2

Li+
NH

Na+
K+
a5

Cs+
Mg2+
Ca2+
a3

Ba2+
Al3+
Fe3+
3 NH a) cone

Ni2+
a1

Cu2+
catio

Co3+
Ag+
ns

Pb2+
Hg2+
NH NH2

Cd2+
4 b) paco

5 N O c) 1,3 alt
11
 Anion receptors
Pr Pr

O N N O Ph
N H H N Ph
N N
H H N
N N O N HN O
O H NH HN
O
NH HN NH HN
NH HN
N N
N N
Pr
NH HN Pr
HN NH HN
NH
NH H
N n-Pr N
n-Pr
N
Pr
N p-Tol
Pr
NH HN
N
O O

HSO4- и H2PO4- HSO4- ,CH3COO- и ReO4- TcO4-

J.L.Sessler
B.F.Myasoedov
Yu.A.Ustinyuk
2007
12
Neutral molecules binding

13
 The role of hydrogen bonds
O H O
Acetic acid dimer
H3C CH3 Übermoleküle
O H O

H
O N O

N N
Melamine - H H
H H
cyanuric acid O N

N N
H H
N N N
Complementarity: H H

- spatial
- functional
14
 Strip
H H H
O N O O N O O N O
H H H H
N N N N N N N N
H H H H H H
O N N O N N O
H H H H
N N N N N N
H H H H
Rosette
H
O N O

H H H H
N N N N
H H
SELF-ORGANIZATION
N N O N N

H H H H
N N N N N N

H H H H
H H
O N O O N O
H H
N N N N N
H H H H
O N N O
G.M.Whitesides H H
N N N
1995 H H
15
 J.M.Lehn
SELF-ORGANIZATION

2 + Cu
N

2 + Cu

Cu+

Self-recognition ! 16
 Self-organization of supramolecular architecures
9+
Me Me Me Me
N Me
N N N
Me
N NN NN N
N N N N
N N N N
6 + 9 Ag+ Me
N NN NN N
Me
N N N N
N N N N
Me Me
N N NN N N N
N N N

Me Me Me Me

3.3 нм NANOCYLINDER from:

3 Linear molecules
4 Plane molecules
12 Cations Cu(I)

17
Self-organization of supramolecular architecures

18
SELF-ORGANIZATION OF AMPHIPHILIC COMPOUNDS

19
20
 Transport metal complexes through liquid chloroform membrane
OH HO
HO OH
OH HO
HO OH
R=C9H19
R
R R R

Giving phase Receiving phase

H2O CHCl3 H2O

H+ H+

OH HO
HO OH
- OH HO
O OH +
R 3+
O
R R R +
2+ + H2O N O
H2O H2O
N HN N N
N O O N Co N
N N
N O O Cu Co N
NH
Cu Cu N N N
N N N
N N O
N
O 21
OH
 
300.0

250.0
O O O O
H H
200.0

N N 150.0

22
100.0

50.0

0.0
NaOAc
O O O O

O OH O O OH
HO OH
NH3 O
OH OH
OH O O
O OH
O
OH OH O
HO
OH OH OH
OH

Transport of compounds from bibliotheka

РМ3 model of complex of of di-, hydroxy- and amino-acids.
РМ3 model of complex of
calixarene
calixarene22
22with
withoxalic
oxalicacid
acid 22
 Transport of compounds from bibliotheka of di-,hydroxy- and amino-acids

NO2
NO2


O O O O
H H
F F
F 140
F
F F OH
F F 120
F F O

миндальная кислота OH
100
O
янтарная кислота
O
80 малоновая кислота HO
OH
гликолевая кислота O O
60 O
щавелевая кислота OH OH
O O 40
OH

H винная кислота OH
H O O
20 ацетат натрия
HO OH
0 глутаминовая кислота OH O

O O O
OH

R R O OH
OH OH

NH3

23
I.S.Rizhkina Supramolecular system – amphiphilic
A.I.Konovalov calix[4]resorcinearenes - surfactant - La(III)
2005.
Supramolecular
Супрамолекулярный
1 O catalyst
катализатор 1 O
R R
P O NO2 + H 2O P OH
HO 2
2
R NO2 R

170 000 times!

24
1 – SYNTHETIC SUPRAMOLECULAR SYSTEMS
Investigation of supramolecular systems
of different architectures with different functions created
on the base of synthetic components

2 – NATURAL SUPRAMOLECULAR SYSTEMS

Investigation of architectures and functions of supramolecular
systems and their components separated from biological
objects

25
 The role of hydrogen bonds
O H O
Acetic acid dimer
H3C CH3 Übermolekül
O H O

H
O N O

N N
Melamine - H H
H H
cyanuric acid O N

N N
H H
N N N
Complementarity: H H

- spatial
- functional
26
 HYDROGEN BINDING OF NUCLEOTIDE BASES

Chemical Adenine Thymine

informatics

Information storage on
Cytosine
molecular level Guanine

but
Information readout on
supramolecular level

27
DNA DOUBLE SPIRAL

H
N
H ADENINE
O N C C N
HC
C C
O P O N N H

O O GUANINE
O

O N H
N

N H
O P O N N
O H
O O
O N THYMINE
O P O N O
O
O H H
N
O N

O P O N O
O
CYTOSINE O
O
O P O

28
DOUBLE SPIRALS

29
 IONPHORES
O
O O

O O
O

Valinomicine 18-crown-6

АМPHIPHILES

30
 Both: in flasks and
in biological systems
receptor – substrate
substrate selectivity
molecular recognition
molecular informatics
transport (ions, molecules)
catalysis
selforganization
architecture

31
 PROCARIOTE CELL
Genetic
apparatus:
DNA

Biosynthetic External cytoplasmic

apparatus: membrane:
mRNA, ribosomes, тRNA Amphiphilic lipids, proteins

Metabolic
apparatus: products
proteins; enzyme
substrates

32
МEMBRANE WORLD supramolecular

supramolecular
RNA WORLD

POLIPEPTIDE WORLD supramolecular

ENZIME WORLD supramolecular

____________________

SUPRAMOLECULAR WORLD

33
«With one or two exceptions,
biological materials are “soft”, that
meaning they combine viscous and
elastic elements. This mechanical
behavior results from self-
assembled supramolecular
structures that are stabilized
by noncovalent interactions.»

34
 IN PROCESS OF EVOLUTION (BIG HISTORY) SUPRA-
NOT BIOLGICAL
MOLECULAR SYSTEMS
SYSTEMS HAVE HAVE BEGUN
APPEARED JUST AFTER
SUPRAMOLECULAR SYSTEMS
APPEAREHCE OF MOLECULES

ON THE CONTRARY

COMMUNITY OF SUPRAMOLECULAR
SYSTEMS HAS BEGUN BIOLOGICAL SYSTEMS

35
Nature used properties of supramolecular
systems for creation of biological systems

But nature have not goal

MAY BE MORE RIGHT

Biological systems are result of self-

organization of supramolecular systems

36
 PROCARIOTE CELL
Genetic
apparatus:
DNA

Biosynthetic External cytoplasmic

apparatus: membrane:
mRNA, ribosomes, тRNA Amphiphilic lipids, proteins

Metabolic
apparatus: products
proteins; enzyme
substrates

37
 Biological systems are result of self-organization
of supramolecular systems

Supramolecular systems are result of self-

organization of molecules

Molecules are result of self-organization of atoms

Atoms are result of self-organization of elementary

particles
___________________________

Self-organization is spontaneous formation of

definite ordered systems
38
 Ability to self-organization is
fundamental property of matter

Paul Davies, The Cosmic Blueprint, 2004

Hermann Haken, Erfolgsgeheimnisse der Natur, 1992

Ilja Prigogine, From Being to Becoming, 1980

Jean-Marie Lehn, Toward Self-Organization

and Complex Matter, 2002

39
Atoms are more complex than elementary particles

Molecules are more complex than atoms

Supramolecular systems are more complex than molecules

Biological systems are more complex than supramolecular systems

MATTER DEVELOPS IN DIRECTION OF GREATER COMPLEXITY

J.-M. Lehn: «Toward complex matter»

P.Davies: «Continued unwrapping of organized
complexity into Universe is fundamental
property of nature»
«Universe is able to creative one-directed
movement ahead even in front of face of
second low»
40
 The hierarchy of structural organization of matter

Atoms a b c

Molecules A(a-a) B(a-b) C(b-c)

covalent bonds

Supramolecular A ….. A A …… B Supermolecules

systems A ……B ….. C Supramolecular

C ….. A assemblies
non-covalent bonds
(intermolecular)

Biological Community of mutually dependent functionally different

systems supramolecular systems

41
Formation of Atoms - properties of elementary particles
There are elementary particles – Atoms will be

Formation of Molecules – properties of Atoms

There are Atoms – Molecules will be

Formation of Supramolecular Systems - properties of

Molecules
There are Molecules – Supramolecular Systems will be

Formation of Biological Systems – properties of

Supramolecular Systems
There are Supramolecular Systems – Biological
Systems will be

LIFE will be !
42
Origin of life is predestinated
(by corresponding conditions)

Life is the form of existence

of supramolecular systems

43
 A.Lima-de-Faria, Evolution without Selection,
Form and Function by Autoevolution ,1988

Biological evolution exists because it was inevitable.

At dawn of Universe proton, neutrino and boson
possessed
. qualities, which made the following
evolution of plants and animals unavoidable.

44
E
106 ev

10 ev

1 ev
ep a m ss bs
bs ?

Arrow of
time,
evolution,
complexity

45
+ ΔE Pre-biological evolution Biological Social
evolution evolution

a m ss bs people
0
1 ev
10 ev

- ΔE 106 ev

46
SELF - ORGANIZATION OF STRUCTURES
____________

SELF - ORGANIZATION OF PROCESSES

Benar cells
Belousov – Jabotincky reaction

_____________

I.Prigogine, H.Haken, P.Davies

47
BENAR CELLS

48
49
50
 BELOUSOV – JABOTINSKY REACTION

CITRIC ACID REDOX PROCESS

KBrO3 KBr
CERIUM SALTS Се(3+) Се(4+)

PINK
BLUE
MECHANISM
PINK
100 stages
BLUE

AUTOOSCILLATION
SELF - SWITCHABILITY
SELF- ORGANIZATION

51
 Prigogine brusselator
I A → X
II B+X → Y+D
III 2X + Y → 3X (autocatalisis)
IV X → E
V A+B → E+D

54
 PROCARIOTE CELL
Genetic
apparatus:
DNA

Biosynthetic External cytoplasmic

apparatus: membrane:
mRNA, ribosomes, тRNA Amphiphilic lipids, proteins

Metabolic
apparatus: products
proteins; enzyme
substrates

55
+ ΔE Pre-biological evolution Biological Social
evolution evolution

a m ss bs people
0
1 ev
10 ev

106 ev
-ΔE

56
 Civilization

Second thermal barrier

Third thermal barrier

Tolerance limit

First thermal barrier

Year
Geological time, mln

* А.I.Zotyn and A.A.Zotyn, Direction, Rate and Mechanisms of Progressive Evolution, Moscow, 1999.
57
+ ΔE Pre-biological evolution Biological Social
evolution evolution

a m ss bs people
0

1 ev
10 ev

106 ev
-ΔE

58
Supramolecular Systems are the
Bridge between nonliving and
living Matter
and
The principal Bases of Life

59
Thank you very much for
your kind attention

60
 The hierarchy of structural organization of matter

Atoms a b c

Self-organization and inceasing of

Molecules
complexity are A(a-a)
not B(a-b) C(b-c)
moving forcies of
covalent bonds
development of matter. Self-organization
is form and increasing of complexity is
Supramolecular
consequence of actionA ….. A A …… B
of properties Supermolecules
of
systems
entities of each level
A ……B of….. Cmatter: to form
Supramolecular

entities of next one. TheseC ….. A properties

assembliesare

moving forcies of development

non-covalent bonds of
matter. (intermolecular)

Biological Community of mutually dependent functionally different

systems supramolecular systems

61
J.-M. Lhen, Toward complex matter: Supramolecular
chemistry and self-organization, 2002

Self-organization (of supramolecular

systems) is driving force that led up to
evolution of the biological world from
inanimate matter

62
САМООРГАНИЗАЦИЯ
САМОСБОРКА
УСЛОЖНЕНИЕ
УПОРЯДОЧЕНИЕ

63
 Supramolecular machines

pH-driven molecular shuttle Photo-driven molecular shuttle

O
O
O O +
O
+ N +
H N
O
+
O N2 O N O
N +
N N O
O + O N
N
O O
N R u II O
N
O O + N O
N O

64
 Artificial ion channel
G.W.Gokel
2001

G.Wu
2005 65
Artificial virus
Y.Aoyama
2005

66
SELF-ORGANIZATION OF AMPHIPHILIC COMPOUNDS

level (i)
Single surfactant solutions

norm al spherical reverse

m icelles m icelles

level (ii)
Liquid crystal

__ __
_ ______
_
norm al rod
m icelles
(surfactant-electrolyte oil/w ater
system s) w ater/oil lam ellar hexagonal
m icroem ulsions m icroem ulsions lyom esophase
lyom esophase

level (iii)
M ulticom ponent system s

- -
-

M ixed m icelles
Surfactant-polym er Polym er-cyclophane
(binary surfactant
system s system s
solutions)
level (iv)
Biological system s

Bilayer Vesicles Bilayer 67

m em branes