The challenge of cyclic and acyclic schiff bases and related derivatives

Abstract

The use of planar or tridimensional cyclic and acyclic Schiff bases, their polyamine homologues and related derivatives, for the formation of mononuclear and especially polynuclear complexes, is reported.

Attention is devoted to the synthetic pathways and to the structural aspects of the resulting systems, particularly the role of the shape of the coordinating ligands and of the different metal ions in directing the synthesis totally or preferentially towards mono-, di- or poly-nuclear entities.

Special care is paid to compartmental ligands, owing to their ability to bind two or more metal ions in close proximity. The insertion of asymmetry into these ligands provides important diversification of the coordinating sites and allows for different and well defined recognition processes involving specific ions and/or molecules at the adjacent coordinating sites.

New molecular materials, devices and probes for specific recognition and detection in the solid state or solution take advantage of the presence of different metal ions at appropriate distances from each other in a preordered stereochemical environment with variation of oxidation state, magnetic, optical and redox properties. Such polynuclear systems can exhibit unusual reactivity or catalysis.

Introduction

Macrocyclic and macroacyclic compounds have attracted increasing interest owing to their role in the understanding of molecular processes occurring in biochemistry, material science, catalysis, encapsulation, activation, transport and separation phenomena, hydrometallurgy, etc. [1], [2], [3], [4], [5], [6], [7], [8].

Many ligands have been designed to mimic the function of natural carriers in recognizing and transporting specific metal ions, anions or neutral molecules and in understanding and reproducing the catalytic activity of metallo-enzymes and proteins [1], [2], [3], [4], [5], [6], [7], [8]. In these studies Schiff bases have been extensively employed and a large variety of planar macrocyclic and macroacyclic ligands have been synthesized to ascertain correctly the role of the different donor atoms, their relative position, the number and size of the chelating rings formed, the flexibility and the shape of the coordinating moiety on the selective binding of charged or neutral species [9], [10], [11].

The evolution of these Schiff bases has produced macrobicyclic ligands obtained in one-step multiple condensation reactions [8], [9], [10]; the cyclic [2+3] Schiff base condensation represents the extension of the [2+2] macrocyclic coordination systems into the third dimension. In addition to the use in the field of molecular recognition, catalysis and transport, these cage molecules are promising in the stabilization of particular species. The nature and disposition of donor atoms in the rigid cage may enhance the stability of unusual oxidation states in the coordinated transition metal ion, while encapsulation may protect normally labile substrate species. This combination of characteristics will eventually permit moisture sensitive chemistry to be carried out in the protected cavity under room temperature and atmospheric pressure.

Pendant arm macrocyclic or macroacyclic ligands and their metal complexes have also attracted attention [12], [13], [14], [15]. Arms bearing additional potential ligating groups have been introduced at both carbon and nitrogen atoms of macrocycles generally based on polyaza- or polyoxa-donor sets, in order to obtain modified complexation properties relative to the corresponding simple macrocyclic or macroacyclic precursors [16], [17], [18].

The introduction of specific functionalities at the periphery of the coordinating moiety gives rise to quite sophisticated systems capable of contemporary multi-recognition processes, specific separation and transport processes across membranes or activation and catalysis in a ecocompatible solvents.

For the macrocycles the hole size represents an additional parameter which may influence greatly the ability to discriminate among the different charged or neutral species to be recognized while for the macroacyclic systems interesting properties may arise from their higher flexibility. These ligands have been primarily designed to form 1:1 complexes. The progressive enlargement of the coordinating moiety allowed studies aimed at a deep understanding of physico-chemical properties arising from the simultaneous presence of two or more metal ion in close proximity within the same coordinating moiety.

Attempts to construct in vitro systems that mimic the catalytic activity of enzymes have produced increasing attention to compounds that contain cavities of sufficient diameter and depth to form host–guest complexes, such complexes constituting the first intermediate in enzyme-model processes.

A wide variety of different compounds (i.e. cavitands, calixarenes, polyporphyrins, polydentate Schiff bases, polyaza, poly-oxamacropolycycles) have been designed to throw light on these problems. Cavitands [9] and calixarenes [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], widely used since the clarification of the phenol-formaldehyde condensation reaction involved in their systems, represent two examples of macrocyclic systems with an enhanced capability to form stable inclusion complexes with both charged and neutral molecules and to act, after suitable functionalization both at upper and lower rings, as selective catalysts. They corroborate the possibility to design bifunctional or polyfunctional ligands capable to secure contemporary cations and anions at the different functionalities and to insert two- or more equal or different metal ions at suitable distances into their coordinating cavities.

In the past, the major interest was towards the most appropriate synthetic procedures for the preparation of dinuclear complexes and their physico-chemical properties in consequence of the close proximity of two metal ions. In particular the preparation of complexes containing two transition metal ions separated by distances of 3–6 Å is of considerable interest. At these distances, no direct interaction between the metal ions is expected, yet a substrate could interact simultaneously with both ions, and it has been shown that pairs of metal ions at suitable distance and/or with an appropriate structure can mediate certain chemical reactions either better than, or in different manner to isolated centers. Thanks to their peculiar properties, these entities offer the necessary tool for a correct molecular understanding of activation, transport and separation of specific molecules with different complexity, of the selective recognition of neutral or charged species, of the modification of appropriate surfaces, etc. They are currently proposed as essential components in the preparation of suitable devices based on specific molecular assembly.

Starting from simple dinucleating ligands, very complex planar or tridimensional cyclic or acyclic systems have been proposed and prepared using self assembling procedures, recognition processes, template effect, etc. Thus polytopic, polyfunctional or polymeric systems, containing also lateral groups bearing additional coordinating functions, redox active groups (as ferrocene), or IR active groups (as Cr(CO)₃) have been prepared and studied in detail. Also the use of particular complexes as ligands for further complexation has been successfully used [5], [9], [10].

The ability of the specific ligand to bind, in appropriate coordination sites, different metal ions is the basic principle for the design of dinucleating or polynucleating ligands.

Many excellent papers have been published during the last two decades on the preparation and properties of dinuclear complexes and the most relevant results have also been reviewed [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50]. In particular, attention was devoted to their correlation with the active site of metallo-enzymes and metallo-proteins containing dinuclear metallo entities in order to elucidate the factors that determine the reversible binding and activation of O₂ in various natural oxygen transport systems and mono- and di-oxygenases and to mimic their activity [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52]. Macrocyclic and macroacyclic ligands have also been used for the generation of compounds with specific spectroscopic and magnetic properties. Complexes containing magnetic metal centers may exhibit magnetic properties which are not simply the sum of those of the individual ions surrounded by their nearest neighbour ligands. These properties result from both the nature and the magnitude of the interactions between the metal ions within the molecular unit.

Using compartmental ligands, binuclear complexes have been synthesized, where the two metal centers, if paramagnetic, interact with each other through the bridging donor atoms of the ligands in a ferromagnetic or antiferromagnetic way. By changing the type of the ligand, the distance between the two chambers and/or the paramagnetic centers, it is possible to vary considerably the magnetic interaction and, with particular complexes, ferromagnetic interactions have been observed. Thus these complexes may be good building blocks for the preparation of molecular magnets.

Complexes in which a single ligand organizes more than two metal centers into some predetermined arrangement, giving rise to unique behaviour, have been also designed, synthesized and fully characterized.

In these studies Schiff bases deserve a relevant role for several reasons:

• They can be obtained by simple self-condensation of suitable formyl- or keto- and primary amine-precursors. Multiple self-condensation processes give rise to complex planar or tridimensional compounds in one step.

• They generally can contain additional donor groups (0, S, P, etc.) and this makes them good candidates for metal ion complexation and for mimicking biological systems.

• Alternatively they can be obtained by template effect, this procedure directly gives the designed complexes. Moreover, these complexes can undergo transmetallation reactions when reacted with a different metal salt; this synthetic procedure allows the formation of not otherwise accessible complexes. Template and transmetallation reactions quite often give rise to the designed complexes in high yield and in a satisfactory purity grade.

• They can be functionalized by inserting appropriate groups in the aliphatic and/or aromatic chains of the formyl- or keto- and amine-precursors.

• They can give rise to reductive decomplexation reactions when treated with appropriate reductants with the consequent formation of the corresponding polyamine derivatives less sensitive to hydrolysis and more flexible. These reduced compounds contain NH groups which may be further functionalized by appropriate synthetic procedures.

• The use of particular Schiff bases can exhibit unusual complexation; for instance helicates derivatives have been obtained with imine derivatives containing appropriate chains and/or suitable donor sets.

• They can be linked to an appropriate support (e.g. silica) giving rise to modified catalysts or modified surfaces, bearing well defined molecular assemblies.

• It is well known that other systems are excellent ligands for specific metal ions (i.e. crown ether, macrocyclic thioether, polyaza derivatives, etc.). Thus the fusion of different coordinating entities (i.e. a Schiff base and crown-ether moiety) into a unique ligand can give rise to very interesting systems capable of multiple selective and/or different metal ions recognition processes.

In recent papers we reported a comprehensive view on these topics, reviewing the most interesting data available [5], [42]. In the present article particular attention is devoted to the most recent progress made in the development of synthetic procedures for the preparation of mono-, di- and poly-nuclear Schiff base complexes and their reduced analogues, together with significant examples of closely related systems, in the study of their physico-chemical properties and in their possible applications.

Special care is devoted to the compartmental ligands, owing to their ability to secure two or more metal ions in close proximity. The insertion of asymmetry into these ligands provides a significant diversification of the coordinating sites and allows different, well defined recognition processes of specific ions and/or molecules at the adjacent coordinating sites and a correct and deep study of the physico-chemical properties arising from these aggregations.

The review basically follows the structure of a previous one published in 1995 [5] and updates the knowledge in this field up to 2002.

It can be divided into two parts. The first part, containing the 2 Schiff bases, 3 Di -or poly-topic systems, 4 Macrocyclic and macroacyclic polyamine ligands, 5 Anion recognition by acyclic and macrocyclic systems, 6 From mononuclear to polynuclear systems, mainly concerns the preparation and properties of the ligands, particularly their ability to act as mono- or poly-nucleating systems, also through additional functionalities that make them di- or poly-topic in nature. The possibility offered by suitable bridging groups to design a chemical pathway, capable of tuning the synthesis from mononuclear to polynuclear complexes and hence to obtain systems with the desired metal nuclearity, is also elucidated. Finally the ability of these systems to give rise to specific recognition, particularly anion recognition, is also considered.

The second part, containing the 7 Mononuclear complexes, 8 Dinuclear complexes with macrocyclic ligands, 9 Dinuclear complexes with acyclic ligands, 10 Polynuclear complexes with symmetric macrocyclic ligands, 11 Polynuclear complexes with asymmetric macrocyclic ligands, 12 Polynuclear complexes with acyclic ligands, 13 Polynuclear complexes with ligands containing ferrocene derivatives, 14 Polynuclear complexes with special acyclic or cyclic ligands, 15 Polynuclear systems containing oxime ligands, deals with the synthesis and properties of acyclic and cyclic complexes; the presentation follows the different nuclearity of the systems, thus the mononuclear complexes are discussed first, then the dinuclear complexes and finally the polynuclear ones. This offers the possibility to evaluate the different physico-chemical properties arising from the increase in metal nuclearity. The presence of different metal ions, in fact, at appropriate distance from each other, in a preordered stereochemical environment and oxidation state, strongly inflences the magnetic, optical and redox properties of these polynuclear systems. Their relevance in obtaining unusual reactivity or catalysis, new molecular materials, devices and probes for specific recognition and detection in the solid state or solution is also considered.

In particular Section 2 is devoted to the role of peculiar formyl- and/or amine-precursors in the synthesis of Schiff bases and related complexes. Moreover the coordination ability of these systems is considered, with a particular emphasis on their ability to give rise to polynuclear systems. Related ligands, containing similar coordination moieties, have been also included in this section in order to give a broader view of the potential of these precursors and also to compare the coordination ability of the different precursors. The self-condensation reaction of these precursors gives rise to cyclic and acyclic Schiff bases which can have different size according to the experimental conditions employed. Moreover the role of the different metal ions as templating agents in directing the synthesis toward a specific Schiff base array is discussed. The parameters influencing ring expansion or ring contraction of the Schiff bases is elucidated. Also the use of transmetallation reactions in the preparation of Schiff bases, especially of those not otherwise obtainable, is reported. The preparation procedures for demetallation of Schiff bases complexes is also considered. Finally the synthetic pathway for obtaining positional isomers and/or migration reactions of specific metal ions from one chamber to another, when compartmental systems are employed, are presented.

In Section 3 the recognition, transport and separation properties of ligands, derived from the addition of specific functionalities to acyclic and cyclic Schiff bases, are taken into consideration. Also the possibility to obtain multiselective coordination processes by tuning the insertion or the addition of coordinating groups at the periphery of the coordination moiety, is discussed.

Section 4 is especially devoted to macrocyclic and macroacyclic polyamine ligands, derived by reduction of the related Schiff bases, together with their ability to coordinate different metal ions. This allows a comparison of the properties of complexes of these ligands with those derived from Schiff bases containing the same denticity but having a different flexibility.

Section 5 deals with the ability of suitable Schiff bases and especially their reduced analogues to recognize, in addition to specific metal ions, well defined anions, leading to potential applications in hydrometallurgy, detoxification, etc.

Section 6 explains the possibility to tune the chemical synthesis toward mononuclear or polynuclear metal complexes by using ligands containing suitable bridging groups (i.e. phenol or thosphenol groups) or appropriate spacer groups.

Section 7 deals with the synthesis and the properties of mononuclear complexes. The survey starts off by taking into consideration the complexes derived from [3+2] tridimensional macrobicyclic ligands, followed by those derived from [2+2] and [1+1] planar macrocyclic ligands. Then the complexes with planar asymmetric cyclic and acyclic ligands, containing additional functionalities, are presented.

The preparation of [2+1] planar and [3+1] tridimensional macrocyclic Schiff bases, derived from 2,5-diformylpyrazole, the supervisor diformyl-tripyrrane homologues and acyclic ligands derived from polyether substituted salicylaldehyde derivatives, are discussed. Moreover the related d- and especially 4f-metal ions complexes and their use in biology and medicine is considered. Finally the possibility to tune the synthesis of mononuclear or polynuclear complexes with acyclic [3+1] ligands is reported.

Section 8 is devoted to homo- or hetero-dinuclear complexes with symmetric and asymmetric macrocyclic Schiff bases, mainly [2+2] cyclic complexes derived from the condensation of 2,6-diformyl-4-substituted phenol or 2,6-diformyl-4-substituted thiophenol with facultative polyamines. The related reduced derivatives are also included. Furthemore complexes derived from macrobicyclic ligands or ligands bearing additional different functionalities (mainly as pendant arms) are reported.

Section 9 deals with dinuclear complexes with end-off symmetric or asymmetric and side-off acyclic ligands. The asymmetric ligands revealed that they were very useful tools for the preparation of pure hetero-dinuclear complexes. In several cases the difference of the two adjacent chambers allows the preparation of pure heterodinculear isomers in one pot without the formation of positional isomers.

In 10 Polynuclear complexes with symmetric macrocyclic ligands, 11 Polynuclear complexes with asymmetric macrocyclic ligands polynuclear complexes with symmetric and asymmetric macrocyclic ligands are reported, respectively. The possibility to tune the synthesis pathway towards complexes with progressively increasing nuclearity, using the same keto- and amine-precursors, deserves particular attention. The use of asymmetric compounds offers additional possibilities for selective metal ion recognition at the different donor sets.

Section 12 reports the synthesis and the properties of polynuclear complexes with acyclic ligands derived from substituted salicylaldehyde, 2,6-diformyl-4-methylphenol or related derivatives. Complexes of Schiff bases containing additional auxiliarities, acyclic or cyclic in nature, are also included.

Section 13 takes into consideration Schiff base complexes and their reduced analogues, bearing a progressively increasing number of ferrocene groups. Systems bearing such redox-active groups (i.e. their possibility to give rise to the ferrocene → ferrocenium reversible reaction) offer a valid chance to their use as switching agents in complexation–decomplexation processes, making feasible their applications in catalysis, material science, hydrometallurgy and in the design of molecular devices.

In Section 14 the possibility of simple Schiff bases to act as di- or poly-nucleating ligands, through the fromation of σ-bonds at the benzene ring, towards specific metal ions (i.e. Pd²⁺, Pt²⁺) is discussed. Moreover, a series of polynuclear complexes with giant macrocycles is reported in order to verify the role of the different coordination moiety on the properties of the resulting complexes.

Finally in Section 15 ligands containing oximes and related homo- and hetero-polynuclear complexes are considered. Particular attention is devoted to the relevant magnetic interaction between identical or different paramagnetic centers mediated by the N–O bridges. In this context the possibility to synthesis trinuclear complexes with an almost linear M–M–M, M–M′–M or M–M′–M″ metal ion assembly is particularly useful for an elucidation of the contribution of the different metal ions to the antiferromagnetic or ferromagnetic behaviour of the resulting complexes. This opens new exciting possibilities in the design of molecular ferromagnets.