Ov
Catechol-Based Biomimetic Functional Materials
Josep Sedó , Javier Saiz-Poseu , Felix Busqué , and Daniel Ruiz-Molina *
Dr. J. Sedó, Dr. D. Ruiz-Molina
Centro de Investigación en Nanociencia y Nanotecnología (CIN-CSIC)
Edifi cio CM7, Campus UAB, 08193
Cerdanyola del Vallès, Barcelona, Spain
E-mail: druiz@cin2.es
Dr. J. Saiz-Poseu
Fundació Privada Ascamm
Parc Tecnològic del Vallès
Av. Universitat Autònoma
23 - 08290 Cerdanyola del Vallès, Barcelona, Spain
Dr. F. Busqué
Departament de Química
Universitat Autònoma de Barcelona
Campus UAB- 08193, Cerdanyola del Vallès, Barcelona, Spain
Abstract.
Catechols are found in nature taking part in a remarkably broad scope of biochemical
processes and functions. Though not exclusively, such versatility may be traced back to several
properties uniquely found together in the o -dihydroxyaryl chemical function; namely, its
ability to establish reversible equilibria at moderate redox potentials and pHs and to
irreversibly cross-link through complex oxidation mechanisms; its excellent chelating
properties, greatly exemplifi ed by, but by no means exclusive, to the binding of Fe 3 + ; and
the diverse modes of interaction of the vicinal hydroxyl groups with all kinds of surfaces of
remarkably different chemical and physical nature. Thanks to this diversity, catechols can be
found either as simple molecular systems, forming part of supramolacular structures,
coordinated to different metal ions or as macromolecules mostly arising from polymerization
mechanisms through covalent bonds. Such versatility has allowed catechols to participate in
several natural processes and functions that range from the adhesive properties of marine
organisms to the storage of some transition metal ions. As a result of such an astonishing
range of functionalities, catechol-based systems have in recent years been subject to intense
research, aimed at mimicking these natural systems in order to develop new functional
materials and coatings. A comprehensive review of these studies is discussed in this paper.
Introduction.
Catechols are benzene derivatives with two neighboring (orto-) hydroxyl groups, ubiquitously
spread in nature. For example, catecholamine neurotransmitters,
[1]
such as adrenaline and
noradrenaline, fulfill essential and well-defined biochemical roles. But catechol derivatives can
also be found as active species in a variety of environments, displaying a remarkable degree of
chemical and physico-chemical versatility that has already inspired, and is still leading to, an
ever-growing number of applications as functional materials. In this regard, this review will
focus on past and recent studies involving the design and biomimetic use of synthetic
catecholic molecules in biomedics, analytical (bio)chemistry, nanotechnology and materials
science, showcasing the unique potential of this chemical functionality to afford
multidisciplinary approaches to scientific research, while offering at the same time promising
candidate structures for technologically relevant applications.
With regard to function, catechols may be broadly classified as follows:
SWITCH, where catechol moieties function as responsive units to external stimuli
SCAFFOLD, where catechol blocks build 2D or 3D structures, either by polymerization
or self-assembly, which are functional on their own
HOOK, in which catechol moieties make up complex systems in which they serve as
individual binding sites to isolated molecules
ANCHOR, where, either as part of complex systems or by themselves, catechol
moieties act as passive links to surfaces and/or covalent supports to other (functional)
moieties
Accordingly, this review has been structured in eight different sections, where the prominent
functional role of the catechol moiety is first exemplified by natural counterparts. In Sections 1
to 4, we will discuss the use of catechol derivatives to anchor molecules and polymers to an
astonishing variety of surfaces (both nano/micro- and macroscopic), which currently constitute
perhaps their fastest growing field of application. Section 5 will present studies where
catechols are shown to polymerize in oxidizing conditions to build up complex, polymeric
scaffolds with excellent properties as surface coatings and incipient potential as functional
materials. The ability of catechol groups to coordinate effectively anionic and cationic species,
but especially transition metals such as Fe
III
, in therapeutic, analytical and environmental
applications will be reviewed in Section 6. Finally, Sections 7 & 8 will deal with examples of the
reversible redox activity of catechols, which together with their strong ability to couple to
other molecules and metals, and their use as stimulus-controlled switches for device
applications.
1. Adhesives.
Mussel-adhesive proteins have been the subject of intensive scientific research over the past
decades,
[2,3,4,5]
particularly because of the remarkable ability of several marine invertebrates to
strongly adhere to virtually all surfaces, -even low-fouling materials, such as paraffin and
Teflon®-,
[4,6]
and more distinctively, to do so in wet conditions that are typically conducive to
adhesion failure.
[4]
In order to pin down the source of this robust adhesion, detailed studies on
the blue mussel (Mytilus edulis) and other sessile species
[7,8]
have been carried out in the past
years. To hold fast to surfaces, mussels secrete a transparent, gel-like proteinaceous substance
that hardens with time into strong adhesive threads, with concomitant darkening.
[9,10]
All five
mussel foot proteins (Mefp) unique to the adhesive plaque, albeit diverse in structure, present
relevant common features, such as recurring sequence motifs,
[11]
but more importantly,
varying amounts of the non-essential catecholic aminoacid DOPA (3,4-
dihydroxyphenylalanine), ranging from 2 to ca. 30%.
[2,
6
,10]
Either free, functionalized in simple
variant forms, or as part of polypeptidic backbones, DOPA is widely distributed in most phyla
of the animal kingdom, where it plays an astounding variety of biochemical roles.
[7]
With
regard to adhesion in Mefps, DOPA was identified by Waite and co-workers as unique in that it
may serve two essential purposes:
[12]
on the one hand, as a catecholic anchor, it is able by itself
to chemisorb to surfaces by using diverse mechanisms, such as metal bidentate
coordination
[13,14,15,16]
and hydrogen bonding;
[3,
4
,11]
on the other hand, it oxidizes easily -both
by chemical and enzymatic methods- to the corresponding DOPA-quinone, which is then able
to act as cross-linking unit, either by reacting with nucleophilic groups in the polypeptidic
matrix by means of Michael-type additions, or via direct free-radical aryl-aryl
couplings.
[
4
,
6
,11, 17 , 18 ]
Other physico-chemical mechanisms, such as - stacking,
[ 19 ]
conformational rearrangements arising from tautomerization mechanisms on side chains
following catechol oxidation,
[ 20 ]
and the presence of other aminoacid residues in the
polypeptidic backbone as coadjuvants of adhesion,
[8,21,22]
have also been cited as contributors
to overall cohesion and adhesion properties shown by Mefps. In an interesting twist of the
versatility of catechol physico-chemistry, recent evidence suggested that bacteria may use
catecholic siderophores –otherwise unrelated to DOPA units in Mefps- to attach themselves to
surfaces in the initial stages of formation of biofilms.
[23,24]
Early attempts at obtaining a wet adhesive biomimic of Mefps were aimed at synthesizing
oligopeptidic analogues based on repetitive aminoacid sequences, and other adhesive
proteins.
[
6
,
9
,25,26]
More recently, a simplified approach based first on random co-polymers with
catecholic moieties
[27,28]
and, alternatively, on carefully designed polymeric scaffolds,
[29]
together with a careful study of the influence of key parameters -DOPA content, nature of
adherend and oxidizing conditions- on the performance of the prospective adhesives,
[27,30]
signified a conceptual leap that provided a solid basis for most recent investigations. For
instance, it was found that whereas adhesion increases roughly proportionally with increasing
DOPA content,
[19,27]
o-quinones exhibit much lower adhesion to metal surfaces than parent
catechols,
[18,19,27,30,31]
and virtually no adhesion to other surfaces, such as mica.
[19]
Therefore,
the successful design of adhesives based on macromolecular materials with pendant DOPA, -or
by extension, catecholic- units would need to strike a balance between interfacial adhesion
and bulk cohesiveness, by finding the degree of overall oxidation that affords an optimal
mixture of catecholic and o-quinoid moieties.
[6,27]
Even when alternative cross-linking
mechanisms have been used, such as Fe
III
-mediated coordination
[32,33]
or photo-curing,
[34]
optimal adhesion still called for a careful adjustment of the extent of cross-linking.
[32,35]
By
contrast, in cases where reactive functional groups in the adherend surface material were
likely to link covalently to the oxidized moieties, such as pig skin
[31]
and an amine-
functionalized Si substrate,
[13]
an increase in the degree of oxidation was shown to enhance
adhesion to the surface, with rupture values in tensile tests consistent with the breakage of
covalent bonds formed in the cross-linking stage.
[13]
This ability of catechol derivatives to interact with surfaces has been exploited by many
scientists worldwide to prepare new synthetic functional adhesives and coatings (vide infra).
However, understanding the basic behaviour and assembly of catechols on surfaces still
remains a challenge. To gain more insight into this issue, Ruiz-Molina et al. have reported new
basic studies studying the self-assembly and interaction of catechols with surfaces by
combined theoretical calculations and scanning tunneling microscopy (STM), which allows the
direct observation of the molecular self-assembly processes on surfaces with molecular
resolution.
[36]
The results indicates that the mechanism for the strong adhesion of catechols on
surfaces is of energetic (interactions on the surface) but mainly of thermodynamic (solvent
effects) origin, opening new insights into the behaviour of catechol molecules on surfaces as
well on 2-D molecular suprastructures. Moreover, the thermodynamic control over the
differential adsorption of an alkylcatechol and the nonanoic solvent molecules has been used
to induce a new temperature-induced switchable interconvesion on surfaces with two
different phases differing in their crystal packing that coexist upon increasing or decreasing the
temperature.
[37]
Alongside excellent specific monographs recently dedicated to this fast-growing subject,
[10,38]
a
survey of representative studies follows, covering recent advances in this research field, and
representing a wide variety of potential applications with technological relevance.
1.1. General purpose adhesives.
Many studies describing more or less simplified synthetic catechol-based polymeric structures
with recognizable biomimetic features have been published in the past decade. Payne and co-
workers described the biomimetic modification of chitosan with dopamine under enzymatic
conditions (tyrosinase). Instead of a protein, the authors chose a polysaccharide with reactive
amino groups as suitable cross-linking matrix via Michael’s-type adducts of the o-quinone
moieties. Although relatively long reaction times were needed, the in situ reaction yielded
chitosan-based water-resistant adhesives with shear strengths up to 400 kPa.
[39]
Wilker et al. prepared a range of copolymers of styrene and 3,4-dihydroxystyrene, thus
replacing the protein backbone with a saturated hydrocarbon chain, and retaining the catechol
unit as the only functional moiety reminiscent of mussel adhesives. Using this very simplified
approach, these synthetic polymers were oxidized in controlled conditions using a variety of
agents, among which, those effective to cross-link the polymer (Fe
III
, periodate, permanganate
and dichromate), showing the formation of adhesive layers. Despite their relatively low
molecular weights, up to 1.2 MPa adhesion shear forces were measured for the copolymer
with an optimized composition.
[28]
Very recently, the same authors reported the synthesis of a
terpolymer of styrene, dihydroxystyrene and p-vinyltolyltriethylammonium chloride aimed at
investigating the role of electrostatic charges in the bulk properties of mussel-mimetic
adhesives, which in Mfp's may be played by lysine moieties. Adhesion values were found to be
lower than those of commercial strong adhesives in dry conditions, but higher in wet
conditions. Particularly, the introduction of ca. 7% of an electrically charged ter-monomer
yielded a polymer with the highest degree of adhesion -2.8 MPa in dry, 400 kPa in wet
conditions on aluminum substrates-, which then decreased with increasing content of this
monomer, probably due to electrostatic repulsion. It was concluded that electrostatic charge
may provide additional surface interaction to increase the adhesion of mussel-foot proteins to
rocky substrates.
[22]
The same authors have recently investigated the optimization of the 3,4-
dihydroxystyrene/styrene ratio in the copolymer, and reported the strongest polymeric mussel
protein mimic reported to date, with adhesion strengths on Al comparable to those of
cyanacrylate glue (7 MPa).
40
The Messersmith group prepared a novel synthetic composite inspired in the composition of
nacre, based on a DOPA-Lys-PEG polymeric cement for the layer-by-layer deposition of ca. 300
nanometer-sized sheets of Na
+
-Montmorillonite clay. Results showed that even small amounts
of the cement were enough to impart good mechanical properties to the composite.
Furthermore, it was shown that the addition of Fe
III
enhanced the mechanical properties of the
material because of DOPA-mediated coordinative cross-linking. The Young modulus of the best
composite approached 7 GPa, comparable to that achieved with single and multi-walled
carbon nanotubes, although still lower than that of natural nacre (ca. 250 GPa).
[41]
The same
research group reported the use of a brush co-polymer to increase the interfacial shear stress
between a metal wire and a polymer matrix. Small wires of NiTi and Ti-6Al-4V were coated
with brushes of polymethylmethacrylate, anchored to the surface by ATRP polymerization
using a brominated dopamine derivative. Coated wires were further cast on a PMMA block
and subjected to a pull test to determine their adhesion to the matrix. Results showed that the
use of the dopamine-based brush coating more than doubled the macroscopic affinity of the
metal wires for the matrix, compared with uncoated wires.
[42]
As part of their research on
biocompatible adhesives, the adhesive properties of catecholic moieties were further
investigated by synthesizing a block methacrylic acid /methylmethacrylate copolymer with
grafted DOPA units. This polymer was then used to fabricate an adhesive elastic membrane,
with which pressure adhesion tests on TiO
2
and pig skin surfaces were carried out. After
repeated contact/removal experiments, adhesion was shown to decrease, likely due to loss of
adhesive material on the membrane that ended up more strongly bound to the adherend
surfaces. Interestingly, while oxidation dramatically decreased adhesion to TiO
2
, it improved
binding to pig skin, probably due to the formation of covalent bonds by chemical reaction
between oxidized DOPA units and the tissue.
[31]
The careful design of a mussel-foot-protein-mimetic polymer with grafted dopamine pendant
groups enabled the design by the Messersmith group of dual biomimetic adhesive surface that
combined the properties of both dry gecko- and wet mussel-foot adhesion. The peculiar
features of gecko feet were modeled by imprinting roughness into an adhesive
polydimethylsiloxane (PDMS) surface in the form of submicrometer pillars. This patterned,
gecko-like adhesive surface was then coated with a 20-nm layer of a mussel-mimetic
dopamine methacrylate/methoxyethyl acrylate copolymer. The adhesion forces of the coated
patterned surface to silicon nitride, titanium and gold were measured by AFM in dry (air) and
wet (underwater) conditions, and compared to those of an uncoated, patterned reference
surface. The authors showed that, while the mussel-mimetic coating increases dry adhesion