RICERCA ITALIANA     

Hierarchical self-assembly of multicomponent supramolecular architectures

Università degli Studi di Catania

Abstract

The aim of this research project is the non-covalent synthesis of complex supramolecular systems employing a wide range of different building-blocks (porphirines, phtalocyanines, calixarenes, alkylammonium salts, bipiridine and phenantroline ruthenium complexes). The project focuses on the hierarchical self-assembly of “smart” supramolecular aggregates (chiral memory), resulting from electrostatic interactions between oppositely charged homo- and etero-components, and on the formation of nanostructured architectures (supramolecular polymers) harnessing intermolecular iterative host-guest inclusion events.
Some of the specific topics that we would like to investigate concern: the control of stoichiometry, tuning of the degree of aggregation/polymerization in response to chemical stimuli, automated microbatch crystallization, structural characterization of intermediates and final products both in solution and in solid state, separation/segregation of ion pairs, control of the stereochemistry, and induction/amplification of chirality. <<<

Principal Investigator

Roberto Purrello Università degli Studi di CATANIA

Research Objectives

The main goal of this research proposal is the design, synthesis and characterization, both in solution and in the solid state, of homo-molecular (porphyrins:porphyrins and calixarenes:calixarenes) and hetero-molecular (calixarenes:porphyrins) aggregates. The hierarchical self-assembly, control of stoichiometry, tuning of the degree of aggregation/polymerization in response to chemical stimuli, automated microbatch crystallization, ion pair separation/confinement, steric and electronic complementarity, control of the stereochemistry, and induction/amplification of chirality are the specific topics that we will investigate.
Collaboration between the Units of Catania, Messina and Trieste stems not only from sharing common research interests, but also from a complementarity of instrumental and synthetic expertise that, owing to a methodological synergy, will allow us to design, prepare, characterize and study novel supramolecular entities. Two different approaches will be employed: classical covalent and non-covalent synthesis. The latter, in fact, is approaching the level of efficiency of traditional covalent-bond chemistry, and it “collaborates” with it for the rational design of suitable building blocks that are able to determine the specific properties of the supramolecular species.
The three Units will collaborate towards the synthesis of:
1) chiral porphyrin complexes;
2) self-assembled calixarene species.

Self-assembled chiral species in aqueous solution.

The objectives to be pursued in this part of the research program are:
a) Modulation of the chiral memory in aqueous solution.
Different works have underlined that the species formed by interactions between opposite charged porphyrins are kinetically inert. If these species form in the presence of chiral templates they can give rise to the so-called “chiral memory” phenomenon. One of the goals of this proposal is the design, synthesis and characterization in solution and in the solid state (in collaboration with the Unit of Trieste) of porphyrin complexes for which it is possible to modulate the chirality induced by suitable templates and memorized from the aggregates.
b) Self-assembly in aqueous solution of cationic or anionic porphyrins with (achiral or chiral) calixarenes bearing opposite charges.
The step-by-step syntheses of tetracationic porphyrins : octaanionic calixarene complexes, starting from the formation of the 1:4 up to the 7:4 species, has been allowed by the kinetic inertness of the complex species: that is complexation is hierarchically controlled. The kinetic control has allowed for obtaining mixed porphyrin complexes having a predetermined sequence. In this project we propose the synthesis of complexes between tetranionic porphyrins and octacationic calixarenes (synthesized from the Unit of Messina). The Unit of Trieste, continuing an ongoing collaboration, will perform the structure characterization in the solid state. In a second phase we will study more complex systems built with preformed cationic calixarene:anionic porphyrins together with opposite charged similar complexes. In addition, it is our intention to study the complexation between chiral calixarenes (cationic and anionic) with opposite charged porphyrins. The relevance of the chirality in these complexes will be presented in the next section, but it is worth anticipating that the latter complexes would be the first, built by means of a non-covalent approach, for which it is possible to design and control sequence, stoichiometry and morphology. Also in this case collaboration between the three Units is indispensable to ensure a rationale development and the success of the project.
c) Organic-Inorganic hybrid chiral complexes
This part of the proposal concerns the spectroscopic and structural studies of the species deriving from the self-assembly (driven from electrostatic interactions) of chiral complexes of ruthenium (cationic) with anionic porphyrins or phtalocyanines. The first chiral complexes to be tested will be well known complexes of ruthenium(II), like those formed with phenantroline or dipyridyl. The presence of the metal complex in addition to supramolecular chirality should also activate energy transfer processes from the metal center to phtalocyanines.

Self-assembly of calixarenes.

The objectives of this part of the research program are:
a) Synthesis of self-assembling calix[5]arenes monomers.
They will be prepared harnessing the known tendency of p-tert-butylcalix[5]arenes to selectively recognize and bind linear alkylammonium ions inside their cavity. Prototypal precursors of these monomers will require a permanent pi-rich cone-shaped calix[5]arene cavity along with a suitably long linear amino-alkylene chain at the lower rim. Exposure of such a precursor to different acids will produce ammonium derivatives, which, owing to their heteroditopic nature, should act both as host and guest, promoting the self-assembly of supramolecular polymers, via iterative intermolecular endo-cavity inclusion events.
b) Formation of calixarene-based chiral non-covalent polymers.
Chirality will be induced and/or amplified either by resorting to suitable mixtures of achiral and chiral ureido-akylammonium-calix[5]arene monomers (“sergeant and soldiers” principle). Alternatively, enantio-pure amino acids or carboxylates employed as counteranions of ureido-alkylammonium-calix[5]arene monomers could behave as chiral promoters.
c) Synthesis of supramolecular systems derived from divergent bis-calix[5]arenes and alkyldiammonium ions.
An additional target that we would like to pursue concerns the preparation and study of non-covalent polymers obtained from complementary homoditopic monomers, namely alpha,omega-alkyldiammonium ions and bis-calix[5]arenes receptors with divergent cavities. First generation bis-calixarenes will be synthesized with different spatial orientation of the two cavities (o-xylyl-, m-xylyl bridge), the second generation ones will be additionally implemented, at their upper rims, with ureido binding sites, which, by capturing the counterions, will ease the formation of the polymer.
d) Synthesis of chiral and achiral water-soluble calix[4]arenes.
This objective will be achieved by exahustive functionalization of calix[4]arenes, either with sulfonate or tetraalkylammonium groups, at the upper rim and at the lower rim with amino acidic residues or piridyl groups. These multi-charged species will be employed as templates during the non-covalent assembly of porphyrin derivatives bearing opposite charges.

The combined expertise of the Research Units of Catania and Trieste will be essential to achieve a throughout understanding and control of the supramolecular systems that are the target of this project. In particular, the Unit of Catania will characterize the complexes in solution by means of fluorescence and circular dichroism, whereas the Trieste Unit will characterize the complexes in the solid state. <<<

Timescale

24 months

National and international background

Molecular recognition is one of the most elegant and specific driven forces that Nature has selected for life machinery to work. The specificity of bio-recognition and bio-organization processes is ruled by (essentially electrostatic) non-covalent interactions and it is based on a remarkable degree of complementarity between the interacting species. This matching involves not only the dimension and shape of the molecular species but also their charge distribution. Non-covalent interactions play a central role in relevant biological processes as the central dogma of molecular genetics (replication?trascriptione?traslation), signal trasduction, selective transport across membranes of metal ions and small ligands, enzymatic reactions or aggregates formation. The high degree of specificity involved in the above processes clearly indicates that molecular complementarity deals not only with dimension and morphology of the interacting species but also with charge distribution. Supramolecular chemistry or, as defined by J. –M. Lehn (1), the chemistry “beyond the molecule” has exploited these principles, underlying that molecular recognition processes are not only intriguing to study per se, but also that they can become a methodological way to design species with well-defined physicochemical properties. In particular, many studies have been devoted to the non-covalent syntheses of supramolecular assemblies driven by self-assembly processes mediated by “weak-bonds” as: van der Waals interactions, hydrogen bonds, p-p interactions, metal ion coordination and pure electrostatic interactions. Differently from the classical covalent syntheses, in this case the specificity of molecular morphology (e.g. intrinsic or induced chirality) and function (e.g. sensors, receptors, selective channels, etc.) is controlled from the molecular properties and peculiarities; i.e. the molecular properties of the single components define and tune the supramolecular properties. The nature of the final species is uniquely determined by the “instructions” (electronic, magnetic, chiral) carried by the various components at the different stages of the assembly. Chirality, in particular, is one of structural features which has a great influence on the physical-chemical properties of molecules. Not only it drives molecular recognition events, but also strongly influences the spectroscopic, magnetic and electric properties of the molecules. The achievement of the handedness control at a supramolecular level is a relevant goal since the potential applications of chiral supramolecular species are manifold and related to different fields: from the synthesis of new materials (it has been shown that the carbon nanotubes can be metallic or semiconducting depending on their chirality (2) and also that supramolecular chirality fosters non-linear optical effects (3)) to biomedical exploitation (as protein detecting arrays (4)). There are different ways to control supramolecular chirality (5-22). The simplest way is by inducing chirality using one chiral component in the synthesis of the supramolecular assembly. Interestingly, it has been shown from different Authors that induction of chirality during the formation of inert complexes allows to memorize the imprinted chirality (that is; chirality is maintained also after removal of the chiral molecular component 18-22). These complexation events are under a hierarchical control. For example, the chiral memory of the porphyrin aggregates is related to the kinetic inertia of the species: addition of the chiral matrix before complexation induces chirality, after the complexation event does not affect the morphology of the aggregates. A reaction controlled by hierarchy is a process in which self-organization of simple elements depends from a specific sequence of single complexation events, leadings to multipart supramolecular architectures (23-25). Kinetic control is very important in self-assembly processes which leads to multi-components species and then requires many steps. Kinetic inertness, in fact, avoids that the intermediate species dissociate to give rise (in the next step) to species having many species with molecular scrambled sequence.
The potentiality of the supramolecular non-covalent syntheses is, therefore, comparable to that of the more traditional chemistry related to the covalent bonds. However, the supramolecular approach can be seen as complementary to the covalent one. In fact, the latter one still represents the key step for the syntheses of the single molecular components designed to determine the wanted specificity of the more complex supramolecular species (obtained with the non-covalent approach).
In particular, the non-covalent synthesis of porphyrin aggregates has different interesting aspects for the possible technological (supramolecular devices as sensors (26), or for non-linear optical effects (27), etc) and biomedical applications (photodynamic therapy (28), protein models (29), etc.) of the resulting supramolecular species. Porphyrins are interesting molecules for various reasons. First of all, these molecules (which are relevant from a biological point of view) have a high molar extinction coefficient value (which allows for working in the micro-molar concentration range). Besides, their spectroscopic properties (both absorption and emission) can be modulated either by metallation or by changing the nature of the functional groups in the meso- position. The introduction of polar functional groups renders these molecules water-soluble; however, owing to the extended aromatic surface, porphyrins always remain quite solvophobic. The latter point is crucial for our approach, because it permits to modulate porphyrins aggregation state in aqueous solution by simply modifying i) the number and type of substituents (10) or ii) the experimental conditions, as ionic strength, pH (i.e. their protonation state) (11). Porphyrin aggregation is driven by specific recognition processes, both in the presence (30) and in the absence (31) of templates (as biopolymers or polytopic receptors like calixarenes). The use of templates in the non-covalent synthesis plays a central role because not only it organizes porphyrins but confers to the assemblies relevant structural features like chirality.In fact, the interactions of achiral porphyrins with chiral matrices is underlined from the appearance of an induced CD signal (ICD) in the absorption region of the porphyrin (Soret band). This is a noticeable advantage because reports on the complexation events, and also because the shape and the intensity of the signals are strongly correlated to the kind of interactions and aggregation state of porphyrins in the supramolecular complex. Recently, it has been considered also the formation of ternary species in which two opposite cahrged porphyrins interact with an anionic chiral template (32). The resulting complexes are kinetically inert and give rise to the so-called chiral memory phenomenon.
The role of the template is therefore crucial to address the non-covalent synthesis towards a refined control of the chemico-physical and structural features of the reaction products.
In particular, water-soluble calix[4]arenes have been employed as templating agents for the organization and assembly of hetero-component supramolecular calixarene/porphyrin species. These complexes present a unique feature, in fact it is the first example of porphirine aggregates in which it is possible ti predetermine the number and the sequence of the units involved (33). Solution and solid state studies allowed to determine their structure, and use their high stability to design multi-metalporphyrin complexes. These supramoelcular species have a wide range of relevant potential applications.
Over the past few decades calixarenes (34) have played a prominent role in the field of host-guest and supramolecular chemistry, owing to the possibility of obtaining highly specific receptors for cationic or neutral moelcules. Their use in selective extraction processes, as sensors or as chromatographic stationary phases, ranges from the analytical and environmental to the food and biomedical fields (35).
Calixarenes have also been used for the development of non-covalent nanostructured multi-component systems (supramolecular polymers, nano-networks, nanotubes, molecular machines) (36-39). Recent studies on the construction of polycapsules, derived from the molecular recognition of alkyldiammonium ions by bis-calix[5]arenebased exo-ditopic receptors, have also been reported (40). Formation of these aggregates relies on a set of weak interactions (cation-p, p-p, van der Waals, hydrogen bond) that all combine to bring and hold together the calixarene cavities and the dication used as an intermolecular linker. To the best of our knowledge, the formation of supramolecular architectures via the selective inclusion of a specific substrate has been, to date, scarcely studied, and there is still a wide and unexplored area of research that need additional investigations. <<<