Alkali Metal Complexes with Organic Ligands

194 Pages·1973·7.51 MB·english

STRUCTURE
AND
BONDING
16
.M-.J Lehn Design of Organic
Complexing Agents
.M .R Truter Structures of Organic Complexes
with Alkali Metal Ions
W. Simon/W. .E Morf/ Organic Complexing Agents
.P Ch. Meier ni Membranes
R.M. Izatt / .D .J Eatoug h / Cation-Macrocyclic Compound
.J.J Christensen Interaction
ilaklA Metal sexelpmoC
htiw Organic sdnagiL
Springer-Verlag Berlin Heidelberg weN York
STRUCTURE
AND BONDING
emuloV 61
Editors: J. D. Dunitz, Zfirich
P. Hemmerich, Konstanz (cid:12)9 J.A. Ibers, Evanston
C. K. Jorgensen, Gen~ve (cid:12)9 J. B. Neilands, Berkeley
D. Reinen, Marburg (cid:12)9 R. J. P. Williams, Oxford
With 57 Figures
galreV-regnifpS
Berlin- Heidelberg" New York 1973
stnetnoC
Design of Organic Complexing Agents. Strategies towards Prop-
erties. J.-M. Lehn ........................................
Structures of Organic Complexes with Alkali Metal Ions.
.M R. Truter ............................................. 17
Specificity for Alkali and Alkaline Earth Cations of Synthetic and
Natural Organic Complexing Agents in Membranes. W. Simon,
W. E. Morf and P. Ch. Meier ............................... 311
Thermodynamics of Cation-Macrocyclic Compound Interaction.
R. .M Izatt, D..1- Eatough and J. J. Christensen ............. 161
Design of Organic Complexing Agents.
Strategies towards Properties*
Jean-Marie Lehn
Institut de Chimie, Universitg Louis Pasteur, ,1 rue Blaise Pascal 67008 Strasbourg,
France
Table of Contents
I. Introduction ................................................... 2
I. .1 Complexation ............................................ .9
1.2. Molecular Recognition ..................................... 3
1.3. Molecular Information .................................... 5
1.4. Metal Cations as Substrates. The Special Case of Alkali and
Alkaline-Earth Cations .................................... 7
II. Design of Organic Ligand Systems for Alkali and Alkaline-Earth
Cations-Strategies .............................................. 7
II.1. Alkali and Alkaline-Earth Cations .......................... 8
II.2. Cation-Ligand Interactions ................................ 9
II.2. Ligand Topology. Topology Control ......................... 11
II.4. Ligand Binding Sites, Site Control .......................... 15
II.5. Ligand Layer Properties. Layer Control ..................... 20
II.6. Solvent Effects. Medium Control ............................ 24
II.7. Effect of Counterions. Anion Control ........................ 24
III. Synthesis of Ligand Systems. Strategies and Results ................ 28
III. .1 Synthetic Strategies ....................................... 25
III.2. Results: Synthetic Organic Ligands ......................... 29
IV. Complexes of Alkali and Alkaline-Earth Metal Cations with Synthetic
Organic Ligands ................................................ 37
IV,1. Synthetic Organic Ligands: Structure and Conformation ...... 37
IV.2. Complexes: Formation, Structure .......................... 39
IV.3. Complexes: Thermodynamic and Kinetic Data ............... 41
IV.4. Stability of the Complexes ................................. 48
IV.5. Complexation Selectivity. Alkali Cations .................... 53
IV.6. Complexation Selectivity. Alkaline-Earth Cations ............ 55
IV.7. Control over DivalentMonovalent Cation Selectivity ......... 35
IV.8. Kinetics of Complexation ................................. 57
IV.9. Medium and Anion Effects ................................. 60
IV.10. Cation TransporL Design of Selective Cation Carriers ......... 61
V. Alkali and Alkaline-Earth Cation Complexation. Applications, Uses... 63
VI. Conclusion ..................................................... 64
VII. References ..................................................... 65
* Dedicated to Professor Edgar Lederer on the occasion of his 65th birthday.
.M-.J Lehn
I. Introduction
The formation of a "complex" species by the association of two or more
chemical entities (having, in general, electronic closed shells) is one of the
most fundamental molecular processes in biology, in chemistry and in
physics. Such a "super-molecule" represents the next higher level of
physical complexity after the nucleus, the atom and the molecule. Its
formation involves bonding interactions which are much weaker than
the usual well defined covalent bonds.
The complexation process is characterized by its thermodynamic and
kinetic stability and selectivity, i.e. by the amount of energy and the
amount of in/ormation brought into operation. Thus, conceptually,
energy (interaction) and information are at the bottom of the recognition
process of one chemical entity by another, and the design of molecular
systems capable of forming stable and selective complexes becomes a
problem in in/ormation storage and readout at the molecular level.
Along the path going from the weak association of two argon atoms
to the extremely complex and highly specific molecular aggregates
present in living systems (enzyme-substrate; conjugate bases and
replication of nucleic acids; protein synthesis; membranes; receptors;
anfibody-hapten... ,1 )2 the complexes of present day organic chemistry
play a central role. Indeed, stability and selectivity, structure and
reactivity are complicated functions ~fo multiple variables. These intially
hidden variables may be revealed by using models, accessible via chemical
synthesis, and conceived in such a way as to allow a separation of the
variables and an analysis of the nature and the form of the function via
structural incrementation. Conversely, if one is able to achieve control
over these variables, it becomes possible to design systems capable of
specific molecular recognition.
Since the central topic of the present chapter is the design of ligands
for the selective complexation of alkali and alkaline-earth cations, we
shall first consider the most general features of such processes.
1.1. Complexation
The interaction between two species A and B (in general closed shell) may
be repulsive or attractive. In the latter case complexation occurs leading
to a more or less strongly bound entity. Although, strictly speaking, in
such a process each species is a ligand for the other one, we shall call
ligand L the species whose complexation properties are under investiga-
tion and whose design and structural variations determine these proper-
ties. The other partner, the complexed species (generally also the smaller
species) may be called the substrate S. Complexation is characterized by
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Design of Organic Complexing Agents. Strategies towards Properties
the stability of the complex, by its mechanisms and rates of formation
and dissociation. The complexation process possesses a given stoichio-
metry n leading to a LSn species: L + uS r LSn.
In the following general discussion n = 1 will be assumed for simplic-
ity. Other stoichiometries will be considered in the text when relevant.
All three species L, S and LS are solvated to various extents.
We may distinguish two limiting types of complexes: addition and
inclusion complexes. Addition complexes are those where L and S
associate without appreciable interpenetration of the molecular shapes.
Inclusion complexes are those where the ligand species defines either a
surface which contains a section (two dimensional inclusion complex) or
a volume which contains all points (three dimensional inclusion complex)
of the complexed speciesl). The two types of inclusion complexes corre-
spond to two types of cavities: those extending mainly in two dimensions
(cavities defined by a closed planar figure, a ring, a toroid) and those
extending in three dimensions (sphere, ellipsoid, cylinder, etc.)Z).
1.2. Molecular Recognition
If the complexation of ligand L with different substrates $1, $2, $3 is
characterized by similar, or identical, thermodynamic and kinetic
parameters, L just distinguishes one S, species from another one (dis-
tinction). However, if the association shows selectivity for a given
substrate S,, leading to the preferred formation of the LSf species, a
specific complex is obtained (selection). The corresponding sdectivity
may be static (thermodynamic; related to the free energies of the dis-
sociated and associated states, to the stability constant) or dynamic
(kinetic; related to the transition state, to the rates of formation and of
dissociation) or both. The specific complex may undergo specific reactions
and/or allow the selective transport of a given substrate (functional
selectivity).
)1 An intermediate case would be a complex in which two large molecules associate
with only partial interpenetration of part of one molecule into a cavity of the
other.
)2 Since more and more inclusion type complexes are being described nowadays, it
may be useful to develop a systematic formulation to distinguish them from
addition complexes. An addition complex may be represented by &, Bl, for
example benzene, trinitrobenzene.
An inclusion complex could be designated by the mathematical symbol of inclu-
sion c, e.g. S c L, i.e. L includes S, It may also be noted that in addition
complexes A and B may be of similar size; however, in inclusion complexes L
is always much larger than S. A more extended systematic formulation of the
different types of complexation processes and complexes may become useful in
the future.
3
J.-M. Lehn
The overall process of molecular recognition may then be considered
to include
.1 a selection process with the formation of a specific complex;
2. a specific unaion.
It is thus a higher form of molecular "behaviour" than selective com-
plexation alone and involves two stages of information input. Enzyme
reactions are examples of such processes, as well as, for instance, drug-
receptor interactions. Two substrates could, in principle, display very
similar thermodynamic and kinetic complexation behaviour (no selection)
but still only one of them may be able to undergo a specific reaction
(because of geometrical differences, for instance) and thus be recognized.
evit~
evisluper
lnoitaxeipmoCI
.lortnoc on ~j "ooitcoit~iD I
r
Selection I
Ltropsoort ~
'-,r ~o~ioo I ~ - ~
Fig. .1 Flow chart for molecular recognition sessecorp
4
ngiseD of Organic Complexing Agents. Strategies towards Properties
1.3. Molecular Information
In order to achieve selective complexation and to perform specific
functions, chemical information has to be stored in L and read out by S.
Information storage may be accomplished in the design of the ligand
system and readout is contained in the dynamics of the complexation
process. These various definitions are interrelated in the flow chart given
in Figure .1
ytiratnemelpmoC between a ligand L and a substrate S will be achieved
for an optimum inormation content of L with respect to a given S.
It will be seen below that various types of "information" may be
stored in a molecule; thus, complementarity amounts to a sort of gener-
alized "lock and key" relationship not limited to steric fit of L and S,
but extending over other molecular features.
Inormation egarotS
The storage of information in the ligand may allow control over the
stability, selectivity, reactivity, and transport (carrier) properties of the
complex. The following molecular and environmental features may serve
for storing chemical information.
.1 Ligand topology; ygolopot :lortnoc
-- dimensionality
-- connectivity
-- shape
-- size
-- conformation(s)
-- chirality
--ligand dynamics; topological, conformational changes; flexibility
with special reference to the topological properties of the complexation
site.
.2 Binding sites; site :lortnoc
-- nature, electronic properties (charge, polarity, polarisability, Van der
Waals attraction and repulsion, etc.)
number
--
-- shape
size
--
-- arrangement (lattice topology)
--reactivity in order to perform reactions and/or allow coupling of
complexation with other processes or reactions.
5
J.-M. Lehn
3. Layer properties; layer :lortnoc
The ligand may act not only via its complexation site, but also by
separating the bound substrate from the external medium and thus ac-
ting as a layer characterized by certain features:
-- thickness, shielding the complexation site from environment,
-- lipophilicity or hydrophilicity as a whole,
, polarity, being either endolipophilic-exopolarophilic (lipophilic com-
plexation site-polar outer surface, as in enzymes) or conversely,
endopolarophilic-exolipophilic (polar interior-lipophilic outer surface).
4. Environment properties; medium lortnoc
The nature of the medium may also have a strong influence on the com-
plexation process via specific or non specific solvation effects on both the
complexed and uncomplexed states. The solvent plays a very important
role both on enthalpy and entropy of complexation. Stability and
selectivity result from a subtle balance between solvation (of both L and
S) and complexation (i. e. "solvation" of S by L).
5. Effect of counterions, anion lortnoc
In the case of charged complexes forming ion pairs, the nature and
properties of the counter-ion will play an important role in two respects:
.1 the effect of cation-anion interaction on the ,complex stability and
selectivity; 2. the effect of medium on the cation-anion interactions.
Ligand-substrate complementarity extends over the various molecu-
lar features noted above. The problem of ligand design is then to analyze
the properties of the substrate to be complexed, to derive the comple-
mentary chemical information to be stored in the ligand, and to devise
and synthesize a ligand system containing the required information.
Inormation Readout
Readout of the ligand information by a substrate is achieved at the rates
with which L and S associate and dissociate; it is thus determined by the
complexation dynamics. In a mixture of ligands L1, L~ ... Ln and
substrates $1, $2 ... Sn, information readout may assume a relaxation
behaviour towards the thermodynamically most stable state of the
system. At the absolute zero temperature this state would contain only
complementary L1S1, LzS2 ... LnSn pairs; at any higher temperature
this optimum complementarity state (with zero readout errors) will be
scrambled into an equilibrium Boltzmann distribution, containing the
corresponding readout errors (LnSn', n#n'), by the noise due to thermal
agitation.
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Design of Organic Complexing Agents. Strategies towards Properties
1.4. Metal cations as Substrates. The Special Case of Alkali and Alkaline-
earth Cations
Within the realm of organic chemistry two principal levels of com-
plexity in the recognition process may be distinguished, depending on
the nature of the substrate: .1 The case of ionic species, especially
monoatomic inorganic cations and anions forming ion-molecule com-
plexes; 2. the case of molecule-molecule association. Interactions between
molecules are generally weak except in the presence of hydrogen bonds,
hydrophobic bonding or strong acceptor-donor character. Monoatomic
ions may interact much more strongly with organic molecules and lead
to stable complexes.
Organic complexes of transition metal cations have been known for
a long time and have been extensively studied. They are often very stable
and their stereochemistry is strongly dependent on the nature of the
central cation. Their biological role is that of oligoelements participating
in specific processes.
Alkali and alkaline-earth cations CA( and AEC) occupy an important
position in matter and in life. In biology, they are present as charge
carriers in ionic processes (cf. the role of Na + and K + in the propagation
of the nerve impulse) and as structure holders gM( ,+2 .)+'~aC
Because of their closed shell, inert gas, electronic structure, AC's
and AEC's are not expected to show strong stereochemical requirements
in complex formation as do transition metal cations. They may be
considered as spherical even in the complexed state. They are thus at the
very first and simplest level of molecular recognition, spherical recognition,
recognition of spherical cations by an organic ligand. The design of such
ligands, the present results and prospects for future studies will be the
subject of the remainder of this chapter.
II. Design of Organic Ligands Systems for Alkali
and Alkaline-Earth Cations-Strategies
Until recently only complexes of low stability were known for AC's even
in the case of anionic chelating ligands (especially in water; Table .)7
Numerous and much more stable chelate complexes of AEC's with
multidentate anionic ligands are known however (see Table .)7 The
complexation constants )3( always follow the stability sequence Ca +2 >
,+~rS Ba2+ and are in general difficult to modify in a progressive, stepwise
fashion. It is obviously of interest to be able to control both stability
and selectivity of AC and AEC complexes, especially the former.
7