Foresight Update 26
Page 2
A publication of the Foresight Institute
Recent Progress: Supramolecular Chemistry by J.-M. Lehn
by Jeffrey Soreff
(Editor's note: In this issue, Jeff Soreff focuses on an ambitious plan for advances in chemistry - as projected in Nobel chemist Jean-Marie Lehn's new book Supramolecular Chemistry - and its relationship to molecular nanotechnology.)
Jean-Marie Lehn, the winner of the 1987 Nobel Prize in chemistry, provides a broad overview of the chemistry of "soft bonds" in Supramolecular Chemistry. Lehn covers a broad variety of structures and functions. Lehn's goal for chemistry is stated clearly: creating "molecular and supramolecular devices."
From the perspective of molecular manufacturing, perhaps the most
crucial is the effect on synthesis. As Lehn writes: "The
contribution of supramolecular chemistry to chemical synthesis
has two main aspects: the production of the non-covalent
supramolecular species themselves and the use of supramolecular
features to assist in the synthesis of covalent molecular
structures." Both of these options can create atomically
precise components useful in molecular mechanisms. Both can
extend to larger 3D structures than are accessible through
traditional synthetic techniques.
Amongst the types of supramolecular species, one of the
distinctions that Lehn makes is between: "(1)
supermolecules, well-defined, discrete oligomolecular species
that result from the intermolecular association of a few
components (a receptor and its substrate(s)) following a built-in
"Aufbau" scheme based on the principles of molecular
recognition; [and] (2) supramolecular assemblies, polymolecular
entities that result from the spontaneous association of a large
undefined number of components..." Supermolecules can
therefore be atomically precise, while polymolecular entities are
more similar to phases or polydisperse polymers.
The assembly of supermolecules requires well defined adhesion
between selected molecules. Lehn sketches some of the factors
necessary for selective binding: "1) steric (shape and size)
complementarity... 2) interactional complementarity... 3) large
contact areas... 4) multiple interaction sites... 5) strong
overall binding..."
At many points in his book, Lehn emphasizes the importance of
information in supramolecular systems, particularly information
embedded in the constituent molecules during their synthesis. The
selectivity of the binding sites in the molecules is a large part
of this information.
In order to design large supermolecules, composed of a large
number of molecules, each in a unique position, one needs to be
able to construct a large variety of binding sites, each binding
very specifically to its complement. At the end of chapter 2,
Lehn writes: "The variety of hydrogen bonding patterns that
may be envisaged makes these interactions a highly versatile tool
for the recognition and orientation of molecules for both
biomimetic and abiotic purposes." In chapters 2 and 3 these
patterns are mostly turned inwards to bind small cations, anions,
and neutral molecules. While these techniques may prove useful in
molecular manufacturing as, for instance, tool holders, the
examples in chapter 9 where the bonds are turned outwards to form
larger supermolecules appear more promising for the construction
of large structures.
A theme where Lehn's research program also applies to components
for molecular manufacturing lies in the design of exoreceptors.
Lehn describes the design of exoreceptors for control of crystal
growth, and for the control of polymolecular structures. He
writes "The fact that polymolecular assemblies define
surfaces on which and through which processes can occur, again
stresses the interest of designing exoreceptors operating at the
interfaces, in addition to endoreceptors embedded in the bulk of
the membranes." From our perspective, the exoreceptors are,
in addition, useful as structural connections within large
supermolecules. Success at the systematic design and synthesis of
exoreceptors would be a substantial help in engineering large
supermolecules.
In addition to selective binding, Lehn emphasizes that the
self-assembly of well-defined structures must have a termination
mechanism. This is essentially the difference between producing a
supermolecule and producing a supramolecular polymer or phase.
This is crucial if we are to use self-assembly for such tasks as
building a strut out of a number of identical subunits. In Lehn's
words "termination control presents a particular
challenge."
The considerations described above are rather general. Lehn also
describes a good deal of work with two specific structural
motifs: macrocyclic and macropolycyclic ethers and amines on the
one hand and metal helicates on the other.
Lehn's goal is stated clearly:
molecular and supramolecular devices
The macrocyclic ethers are variations on crown ethers. Lehn
describes a large number of cases where they bind substrates
specifically. In one case, "Receptor molecules possessing
two binding subunits located at the two poles of the structure
will complex preferentially substrates bearing two appropriate
functional groups at a distance compatible with the separation of
the subunits. The distance complementarity amounts to a
recognition of molecular length of the substrate by the receptor.
Such linear recognition by ditopic receptors has been achieved
for both dicationic and dianionic substrates, diammonium and
dicarboxylate ions respectively; it corresponds to the binding
modes illustrated in 50 and 51." In this case both the
substrate and the binding site have an obvious tunable element,
so it is quite clear that a variety of specific bindings are
feasible.
The metal helicates that Lehn built are strands of bipyridine
ligands, strung together with alkane or ether linkages and wound
around metal ions. Lehn designed the strands so that a single
strand does not wind around all of the coordination sites of a
single metal ion, but rather two or three strands wind around a
line of metal ions.
Lehn writes: "One may draw an analogy between nucleic acids
and helicates, with on one side the polynucleotide strands and
their interaction through hydrogen bonding and on the other side
the oligobipyridine strands and their binding together via metal
ion coordination." Another way to view the analogy is that
in both cases the noncovalent interactions wind fairly flexible,
readily synthesized, covalent structures into more densely
interconnected, less flexible, 3D structures with very
predictable "secondary structure." Perhaps the metal
helicates might one day be used to build structures similar to Nadrian
Seeman's DNA polyhedra. Lehn has already used these
structures to place substituents on the bipyridine strands into
well defined positions in space.
A crucial feature of nucleic acids is their sequence specific
binding. Seeman's polyhedra use this, and a general use of Lehn's
metal helicates for 3D structures would require some similar
specificity. Since the bipyridine sequences in the helicates bind
to each other through intermediate metal atoms, this requires
that there be sufficiently specific binding of at least two
different types of metal atoms to two different type of
bipyridine sites. Lehn describes an experimental demonstration of
the selectivity of metal ion assembly of helicate structures
with: "Similarly, when a mixture of the two tris-bipyridine
ligands 129 and 148 is allowed to react simultaneously with
copper(I) and nickel(II) ions, only the double helicate 132 and
the triple helicate 149 are formed (Figure 49). Thus, parallel
operation of two programmed molecular systems leads to the clean
self-assembly of two well-defined helical complexes from a
mixture of four components in a process involving the assembly of
altogether 11 particles of four different types into two
supramolecular species."
Lehn describes a number of advantages of metal-centered
supermolecule design in general. He favors it because, amongst
other features, 1) It allows a wide range of bond strengths. 2)
It allows several coordination geometries, with well-defined
orientation of the ligands within each choice of geometry.
In describing supramolecular assistance to covalent synthesis,
Lehn describes a number of selective catalysts, primarily drawing
examples from his group's macrocycle work. He shows examples of
chiral recognition and regiospecificity. Since the catalysts that
he shows have their geometry defined by covalent bonds rather
than by the hydrophobic effects that contribute to the folding of
protein enzymes, one might expect these new catalysts to be more
useful in a machine phase environment than proteins are. Lehn
writes: "Supramolecular catalysts are by nature abiotic
chemical reagents that may perform the same overall processes as
enzymes, without following the detailed pathway by which enzymes
actually effect them or under the conditions in which enzymes do
not operate. Furthermore and most significantly, this chemistry
may develop systems realizing processes that enzymes do not
perform while displaying comparable high efficiencies and
selectivities."
For construction of large structures, nanotechnology requires
catalysis of bond formation rather than bond cleavage. Lehn
writes that "To this end, the presence of several binding
and reactive groups is essential," since at least two
substrates must be bound. Lehn demonstrated this in a macrocycle
that catalyzes the formation of pyrophosphate from two separate
substrates bound at two sites in the macrocycle. This showed
that, while there is a minimum complexity required in a catalyst
for bond formation, this is achievable.
In addition to synthetic techniques, there are a number of other
areas of commonality between Lehn's research program and the
program needed for molecular manufacturing.
There is a common dependence on computation in both areas of
research. Certain functional features, notably allostery, require
at least one flexible degree of freedom in a receptor molecule.
Lehn writes "Such designed dynamics are more difficult to
control than mere rigidity, and the developments in
computer-assisted molecular design methods, allowing the
exploration of both structural and dynamical features, may
greatly help [1.38-1.50]." This is essentially the same
reason that molecular dynamics is employed in analysis of
diamondoid mechanisms. It permits explorations of dynamics which
are an essential part of the functions of the mechanisms.
Lehn presents an architecture for transferring molecular
information across a membrane via "molecular transmembrane
rods". This proposal shares some important common features
with rod logic, albeit in the analog domain. Both proposals pack
desired degrees of freedom very densely, with separate channels
for each rod. The packing of information is somewhat similar to
the design of a binding surface, but, unlike the binding surface
case, the information isn't frozen at the time of covalent
synthesis. As Lehn writes: "Indeed with only a few molecular
rods an extremely large amount of information may be expressed
since the set of rods can adopt a very high number of
topographies defined by in-plane configurations and out-of-plane
displacements."
Lehn writes of the desirability of "the development of
chemo-mechanical actuators for the conversion of light,
electrical, or chemical energy into mechanical energy and motion,
a major goal being, as already pointed out, to achieve controlled
oriented motion." This goal is equally important in the
development of molecular manufacturing systems, since they
require mechanical energy for mechanosynthesis and other
applications.
Some of the experimental work that Lehn describes may already
allow an experimental check on some of the calculated properties
of certain pieces of molecular machinery. Lehn writes:
"...the relaxation data for the free and complexed species,
indicate that complexes of alpha-cyclodextrin present weak
dynamic coupling between substrate and receptor... Potential
energy calculations have shown that there are small or no
barriers to rotation of a substrate inside the cavity of alpha-,
beta-, or gamma-cyclodextrin." The cyclodextrin complexes
may therefore provide an experimentally accessible system for
demonstrating the low barriers predicted for certain types of
bearings useful in nanotechnology. The existence of these
complexes is helpful in showing that the intermolecular
potentials required for low rotational barriers are compatible
with high enough net binding to form stable complexes.
In this book, Lehn shows himself to be a vigorous advocate of the
self-assembly path to nanoscale structures, responding to the
classic Feynman quote "there's plenty of room at the
bottom," with his own view that in "reaching higher
levels of organization and behaviour, it is clear that through
supramolecular chemistry "there's even more room at the
top!" Foresight members interested in the self-assembly
route to molecular nanotechnology will want to watch for further
results from this visionary chemist.
Supramolecular Chemistry. Concepts and Perspectives.
Jean-Marie Lehn. VCH. Weinheim, New York, Basel, Cambridge, Tokyo
1995 271 pp, ISBN 3-527-29311-6, paper $39.95
Book Review: Quotes from Jean-Marie Lehn
Nobel prizewinning chemist Jean-Marie Lehn gives his views on
the future of chemistry in his new book Supramolecular
Chemistry: Concepts and Perspectives. (See adjoining review by Jeff
Soreff.) Foresight director Chris Peterson presents her favorite
quotes from the book as part of the review.
"Recent lines of investigation concern self-processes
(self-assembly, self-organization, replication) and the
design of programmed supramolecular systems."
page 7
"The combination of receptors, carriers and catalysts,
handling electrons, ions, and molecular substrates, with
polymolecular organized assemblies, opens the way to the
design of molecular and supramolecular
devices and to the elaboration of chemical microreactors and
artificial cells." page 87
"Positional changes of atoms in a molecule or
supermolecule correspond on the molecular scale to mechanical
processes at the macroscopic level. One may therefore imagine
the engineering of molecular "machines" that would
be thermally, photochemically or electrochemically
activated" [references, including Nanosystems].
page 135
"The formation of photonic, electronic, ionic switching
devices from molecular components and their incorporation
into well-defined organized assemblies represents the next
step towards the development of circuitry and functional
materials at the nanometric scale...The controlled build-up
of such architectures requires the ability to direct self-assembly
and self-organization processes through explicit
instructed procedures."
pages 137-8
"In addition, temporal information may be involved if
the progressive build-up of the final superstructure occurs
through a defined sequence of molecular instructions and
algorithms, a given component or recognition event coming
into play at a well-defined stage in the overall
process...Such sequential self-assembly represents the next
step in the design of artificial systems presenting higher
levels of complexity." page 144
"With increasing control being achieved over molecular
programming of supramolecular structure generation through
hydrogen bonding, the self-assembly of a variety of linear,
two- or three-dimensional architectures may be
realized...Designed self-assembly thus opens roads towards
the generation of organized entities in the liquid
phase." page 165
"By increasing the size of its entities, nanochemistry
works its way upward towards microlithography and
microphysical engineering, which, by further and further
miniaturization, strive to produce ever smaller
elements." page 195
"'Intelligent', functional supramolecular materials,
network engineering and polymolecular patterning are the
subject of increasing activity in chemical research. The
development of advanced materials may take full advantage of
the control provided by information-dependent supramolecular
processes for the production of large scale architectures in
a sort of molecular and supramolecular tectonics...leading
to a nanotechnology and nanomaterials or
organic or inorganic nature" [references, including Nanosystems].
page 195
"It is important to note that technologies resorting to
self-organization processes should in principle be able to
bypass microfabrication procedures by making use of the
spontaneous formation of the desired superstructures and
devices from suitably instructed and functional building
blocks. There is indeed a rich palette of structures and
properties to be generated by blending supramolecular
chemistry with materials science!"
page 195
"Components and molecular devices such as molecular
wires, channels, resistors, rectifiers, diodes, and
photosensitive elements might be assembled into nanocircuits
and combined with organised polymolecular assemblies to yield
systems capable ultimately of performing functions of
storage, detection, processing, amplification, and transfer
of signals and information..." page 196
"The reading of molecular information and the operation
of molecular devices require ways and means of addressing
molecular and supramolecular species. Despite the difficult
problem that one may apprehend, encouraging and exciting
developments may be anticipated. Indeed, scanning tunneling
microscopy (STM) and atomic force microscopy (AFM) are
providing extraordinary manipulative power at the atomic and
molecular scale..." page 196
"The chemist finds illustration, inspiration and
stimulation in natural processes, as well as confidence and
reassurance since they are proof that such highly complex
systems can indeed be achieved on the basis of molecular
components." page 205
"Questions have been addressed about which one may
speculate, let one's imagination wander, perhaps even set
paths for future investigations. However, where the answers
lie is not clear at present and future chemical research
towards ever more complex systems will uncover new modes of
thinking and new ways of acting that we at present do not
know and may even be unable to imagine." pages 205-6
"The perspectives are definitely very (too?) wide and it
will be necessary to distinguish the daring and visionary
from the utopic and illusionary! On the other hand, we may
feel like progressing in a countryside of high mountains: the
peaks, the goals are visible and identifiable or may become
so as progress is made, but we do not yet know how to reach
them. We may find landslides, rockfalls, deep crevices,
tumultuous streams along the way, we may have to turn around
and try again, but we must be confident that we will
eventually get there. We will need the courage to match the
risks, the persistence to fill in the abyss of our ignorances
and the ambition to meet the challenges, remembering that
'Who sits at the bottom of a well to contemplate the sky,
will find it small'"(Han Yu, 768-824). pages 205-6
This last quotation from Lehn is good advice for those of us
pursuing molecular nanotechnology. The path is unclear, but our
goal is clear. Being reminded of the need for persistence by a
Nobel chemist is reason alone to keep this book on our shelves.
--Chris Peterson
Thanks
Special thanks this issue go to Gayle Pergamit for advising on
the Senior Associates Gathering program; Russell Whitaker, Ted
Kaehler, Wayne Gramlich, and Paul Haeberli for Web Enhancement
code or software evaluation; Dale Amon for providing a mirror
site in Europe for Foresight's web site; Al Globus for briefing
us on nanotechnology at NASA; and Toru Yao for news on
nanotechnology in Japan.
For sending information, we thank Jeff Cavener, Dave Forrest,
G.A. Houston, Marie-Louise Kagan, Tom McKendree, John McPherson,
John Papiewski, Patrick Salsbury, PC Theriault.
--Chris Peterson, Director
From Foresight Update 26, originally published 15 September 1996.
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