Acyclic oligopyrroles as building blocks of supramolecular assemblies

The supramolecular chemistry of acyclic oligopyrrole derivatives mainly reported by the author’s group in the last four years has been summarized in this review. The author has demonstrated the “first step” to construct the new materials and concepts based on the new molecular systems consisting of pyrrole rings, which form the complexes, assemblies, and organized structures, by using noncovalent interactions such as metal coordination, hydrogen bonding, and π–π interaction. Acyclic π-conjugated oligopyrroles have exhibited not only host–guest binding behaviors in solutions but also the formation of, for example, (i) metal coordination polymers to give emissive colloidal spheres, (ii) solid-state assemblies of acyclic π-conjugated anion receptors and their anion complexes, (iii) anion-responsive supramolecular gels from the receptors with aliphatic chains, and (iv) solvent-assisted organized structures like vesicles derived from amphiphilic anion receptors.     

Multi-use NBD-based tetra-amino macrocycle: fluorescent probe for metals and anions and live cell marker

Ligand L (4-(7-nitrobenzo[1,2,5]oxadiazole-4-yl)-1,7-dimethyl-1,4,7,10-tetra-azacyclododecane) is a versatile fluorescent sensor useful for Cu(II), Zn(II) and Cd(II) metal detection, as a building block of fluorescent metallo-receptor for halide detection, and as an organelle marker inside live cells. Ligand L undergoes a chelation-enhanced fluorescence (CHEF) effect upon metal coordination in acetonitrile solution. In all three complexes investigated the metal cation is coordinatively unsaturated; thus, it can bind secondary ligands as anionic species. The crystal structure of [ZnLCl](ClO(4)) is discussed. Cu(II) and Zn(II) complexes are quenched upon halide interaction, whereas the [CdL](2+) species behaves as an OFF-ON sensor for halide anions in acetonitrile solution. The mechanism of the fluorescence response in the presence of the anion depends on the nature of the metal ion employed and has been studied by spectroscopic methods, such as NMR spectroscopy, UV/Vis and fluorescence techniques and by computational methods. Subcellular localization experiments performed on HeLa cells show that L mainly localizes in spot-like structures in a polarized portion of the cytosol that is occupied by the Golgi apparatus to give a green fluorescence signal.     

Synthesis, spectroscopic characterization and DNA nuclease activity of Cu(II) complexes derived from pyrazolone based NSO-donor Schiff base ligands

Two neutral mononuclear Cu(II) complexes have been prepared in EtOH using Schiff bases derived from 4-toluoyl pyrazolone and thiosemicarbazide. Both the ligands have been characterized on the basis of elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. The molecular geometry of one of these ligands has been determined by single crystal X-ray study. It reveals that these ligands exist in amine-one tautomeric form in the solid state. Microanalytical data, Cu-estimation, molar conductivity, magnetic measurements, IR, UV-Visible, FAB-Mass, TG-DTA data and ESR spectral studies were used to confirm the structures of the complexes. Electronic absorption and IR spectra of the complexes suggest a square-planar geometry around the central metal ion. The interaction of complexes with pET30a plasmid DNA was investigated by spectroscopic measurements. Results suggest that the copper complexes bind to DNA via an intercalative mode and can quench the fluorescence intensity of EB bound to DNA. The interaction between the complexes and DNA has also been investigated by agarose gel electrophoresis, interestingly, we found that the copper(II) complexes can cleave circular plasmid DNA to nicked and linear forms.     

Designing cytokine variants by phage-display

Cytokines are important mediators of many cellular functions including coordination of the immune system and regulation of regenerative processes. Therefore, cytokines can be exploited for therapeutic strategies. Cytokines can be altered in a way that their biologic activity is enhanced or antagonized. This can be accomplished by changing the interaction of cytokines with their cognate cytokine receptor complexes. Therefore, many research groups tried to design cytokines, which bind with higher affinity to their receptors. Alternatively, cytokine variants have been created which do bind to their receptors but do not elicit a signal. Such strategies have been followed using high throughput techniques like error-prone polymerase chain reaction and phage display. Designer cytokines can be used to specifically inhibit cytokine functions. Moreover, peptides have been generated with the help of phage display techniques, which exhibit cytokine activity. Surprisingly, such mimetic peptides do not show any sequence similarity to the parental cytokines. Such peptide mimetics can be used as lead structures for the generation of non-peptidic chemical compounds with cytokine activity.     

Recognition of alkali metal halide contact ion pairs by uranyl-salophen receptors bearing aromatic sidearms. The role of cation-pi interactions

Hard anions have long been known to bind strongly to the uranium of uranyl-salophen complexes. Upon functionalization of the salophen framework with one or two benzyloxy substituents, efficient ditopic receptors for alkali metal ions are obtained. The solid-state structures of complexes formed by the two-armed receptor 1 with CsF and with the chlorides of K+, Rb+, and Cs+ reported here reveal the existence of dimeric supramolecular assemblies in which two receptor units assemble into capsules fully enclosing (MX)2 ion quartets. In addition to the strong coordinative binding of the anion to the uranyl center and to electrostatic cation-anion interactions, stabilizing interactions arise from coordination of each cation to six oxygens, three from each receptor, and most importantly, to two aromatic sidearms belonging to different receptors. There are marked differences in organization at the supramolecular level in the CsCl complex of the one-armed receptor 3, in that four uranyl-salophen units instead of two are assembled in a capsule-like arrangement housing a (CsCl)2 ion quartet. However, both receptors achieve the common goal of having each metal cation in close contact with carbon atoms of two aromatic rings. 1H NMR data provide strong evidence that cation-pi(arene) interactions with the sidearms participate in binding also in solution.     

HADDOCK: a protein-protein docking approach based on biochemical or biophysical information

The structure determination of protein-protein complexes is a rather tedious and lengthy process, by both NMR and X-ray crystallography. Several methods based on docking to study protein complexes have also been well developed over the past few years. Most of these approaches are not driven by experimental data but are based on a combination of energetics and shape complementarity. Here, we present an approach called HADDOCK (High Ambiguity Driven protein-protein Docking) that makes use of biochemical and/or biophysical interaction data such as chemical shift perturbation data resulting from NMR titration experiments or mutagenesis data. This information is introduced as Ambiguous Interaction Restraints (AIRs) to drive the docking process. An AIR is defined as an ambiguous distance between all residues shown to be involved in the interaction. The accuracy of our approach is demonstrated with three molecular complexes. For two of these complexes, for which both the complex and the free protein structures have been solved, NMR titration data were available. Mutagenesis data were used in the last example. In all cases, the best structures generated by HADDOCK, that is, the structures with the lowest intermolecular energies, were the closest to the published structure of the respective complexes (within 2.0 A backbone RMSD).     

Paramagnetic cobalt(II) as an NMR probe of dendrimer structure: mobility and cooperativity of dendritic arms

Cobalt(II) has been utilized as an external paramagnetic (1)H NMR probe for the study of the structure of dendrimers that possess specifically located metal recognition sites. The hyperfine-shifted (1)H NMR signals of the Co(II) complexes of several 2,6-diamidopyridine-containing dendrimers have been fully assigned by means of 1D and 2D NMR techniques, including NOE difference, EXSY, COSY, and TOCSY. Temperature-dependent T(1) values of the hyperfine-shifted signals were used to conclude that the Co(II)-dendrimer complexes are in the "liquidlike" regime, indicative of a shell-like structure instead of a "dense-core" structure. The presence of sizable cavities within the dendrimers was observed including a loosely packed conformation for the 2,6-diamidopyridino moiety to bind to potential guest molecules. Cooperativity among the dendritic arms in metal binding is also observed, whereby two dendritic arms bind to the metal center at the same time. In the case of dendrimers with the metal binding site located near the surface of the molecule, such binding cooperativity is still observed despite the large degree of freedom of the metal-binding moiety. Cooperativity among the dendritic arms can thus be considered an intrinsic property, which has to be taken into consideration in future design of functional dendrimers for the purpose of specific recognition and catalysis. The hydrodynamic radii of these dendrimers have been determined by means of nuclear Overhouser effect at low temperature. The study offers a method for the study of the dynamics of dendrimers in solution under different conditions and upon ligand binding and recognition. The study also provides a tool for monitoring systematic variation of the metal binding site in different dendrimer frameworks for specific applications, such as catalysis and molecular recognition.     

Glyphosate and ATP binding by mononuclear Zn(ii) complexes with non-symmetric ditopic polyamine ligands

Binding of Zn(ii) by the ditopic ligands L1py, L2py and L1para, composed of a cyclam unit linked to the linear polyamines 1,4,8,11-tetraazaundecane (L1py and L2para) and 1,4,7-triazaheptane (L2py) via a 2,6-dimethylpyridinyl (L1py and L2py) or a 1,4-dimethylbenzyl spacer (L2para), has been analyzed by means of potentiometric and (1)H and (13)C NMR measurements. All ligands form stable mononuclear Zn(ii) complexes in a wide pH range, featuring the metal ion bound to the macrocyclic unit. The open-chain polyamine unit can easily bind several protons in aqueous solution affording protonated metal complexes at neutral and acidic pH values. These complexes behave as bifunctional receptors for the anionic substrates N-(phosphonomethyl)glycine (glyphosate or PMG) and ATP. Potentiometric, (1)H and (31)P NMR measurements show that the Zn(ii) complex with L1py is the better receptor for both substrates, thanks to the simultaneous presence of a pyridine linker functionalized at its 2,6 positions and of a flexible linear tetraamine chain. In fact, these structural features allow a stronger interaction of PMG and ATP with both the protonated tetraamine moiety and the Zn(ii)-cyclam core.     

Structure, bonding, and reactivity of Ti and Zr amidate complexes: DFT and X-ray crystallographic studies

Easily prepared and highly modular organic amide proligands have been used to synthesize a series of new bis(amidate)-bis(amido) Ti and Zr complexes via protonolysis. These complexes have been structurally characterized by NMR spectroscopy and X-ray crystallography. The solid-state molecular structures of these complexes indicate that the amidate ligands bind to the metal centers in an exclusively bidentate fashion, resulting in discrete monomeric species. Geometric isomerism in these species is highly dependent upon the steric characteristics of the proligands utilized in the synthesis. In solution, these complexes are observed to isomerize on the NMR time scale, with one isomer being predominant. Bonding in the bis(amidate)-bis(amido) complexes was investigated by DFT calculations. The geometric isomers predicted by theory matched the experimentally observed results, within experimental error. The orbitals associated with amidate-metal bonding are energetically well below the frontier orbitals. The HOMO in these complexes is a pi orbital associated with amido ligand-to-metal bonding character, while the LUMO in all cases is a vacant d orbital on the metal center.     

Multi‐Use NBD‐Based Tetra‐amino Macrocycle: Fluorescent Probe for Metals and Anions and Live Cell Marker

Ligand L (4‐(7‐nitrobenzo[1,2,5]oxadiazole‐4‐yl)‐1,7‐dimethyl‐1,4,7,10‐tetra‐azacyclododecane) is a versatile fluorescent sensor useful for Cu^II, Zn^II and Cd^II metal detection, as a building block of fluorescent metallo‐receptor for halide detection, and as an organelle marker inside live cells. Ligand L undergoes a chelation‐enhanced fluorescence (CHEF) effect upon metal coordination in acetonitrile solution. In all three complexes investigated the metal cation is coordinatively unsaturated; thus, it can bind secondary ligands as anionic species. The crystal structure of [Zn L Cl](ClO₄) is discussed. Cu^II and Zn^II complexes are quenched upon halide interaction, whereas the [Cd L ]²⁺ species behaves as an OFF–ON sensor for halide anions in acetonitrile solution. The mechanism of the fluorescence response in the presence of the anion depends on the nature of the metal ion employed and has been studied by spectroscopic methods, such as NMR spectroscopy, UV/Vis and fluorescence techniques and by computational methods. Subcellular localization experiments performed on HeLa cells show that L mainly localizes in spot‐like structures in a polarized portion of the cytosol that is occupied by the Golgi apparatus to give a green fluorescence signal.     

Kinetically inert transition metal complexes that reversibly bind to DNA

Transition metal complexes that reversibly bind to DNA have been studied for almost 30 years. In the last few years a variety of new systems have been developed, employing a range of metal ions and ligand architectures. In many cases, high affinity binding and specific selectivities have been observed. These complexes display properties that make them attractive as probes of DNA structure and function, suggesting that they may find a r?le as prototypical tools for a spectrum of applications, from basic molecular biology to medicine. This review presents an overview of some of the structures and properties of such complexes.     

First palladium(II) and platinum(II) complexes from employment of 2,6-diacetylpyridine dioxime: synthesis, structural and spectroscopic characterization, and biological evaluation

Employment of the monoanion of 2,6-diacetylpyridine dioxime (dapdoH(2)) as a tridentate chelate in palladium(II) and platinum(II) chemistry is reported. The syntheses, crystal structures, spectroscopic and physicochemical characterization, and biological evaluation are described of [PdCl(dapdoH)] (1) and [PtCl(dapdoH)] (2). Reaction of PdCl(2) with 2 equivs of dapdoH(2) in MeOH under reflux gave 1, whereas the same reaction with PtCl(2) in place of PdCl(2) gave 2 in comparable yields (70-80%). The divalent metal center in both compounds is coordinated by a terminal chloro group and a N,N',N"-tridentate chelating (η(3)) dapdoH(-) ligand. Thus, each metal ion is four coordinate with a distorted square planar geometry. Characterization of both complexes with (1)H and (13)C NMR and UV-vis and electrospray ionization mass spectroscopies confirmed their integrity in DMSO solutions. Interaction of the complexes with human and bovine serum albumin has been studied with fluorescence spectroscopy, revealing their affinity for these proteins with relatively high values of binding constants. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA, and the corresponding DNA binding constants have been evaluated. Cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through intercalation, which has been also shown by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have revealed the ability of the complexes to displace the DNA-bound EB, suggesting competition with EB. The combined work demonstrates the ability of pyridyl-dioxime chelates not only to lead to polynuclear 3d-metal complexes with impressive structural motifs and interesting magnetic properties but also to yield new, mononuclear 4d- and 5d-metal complexes with biological implications.     

CH...anion interaction in BF2 complexes of C3-bridged oligopyrroles

Alkyl-substituted derivatives of 1,3-dipyrrolyl-1,3-propanedione BF2 complexes, the efficient receptors for halide and oxoanions with use of bridging CH as well as pyrrole NH, are reported. BF2 complexes with only one pyrrole NH interaction site (2d,e), which exhibit smaller affinities than the basic structure (2b), bind anions tightly, which is inferred by UV/vis absorption spectral changes, compared to the derivatives with an alkyl group at the bridging carbon (2f) or two pyrrole nitrogen sites (2c). With use of 1H NMR and theoretical studies for anion complexes of 2d and 2e, bridging CH (and one beta-CH in 2d) as well as pyrrole NH is found to interact with anions.     

Crown ether appended cyclam receptors for cationic guests

A series of crown ether appended macrocyclic amines has been prepared comprising benzo-12-crown-4, benzo-15-crown-5, or benzo-18-crown-6 attached to a diamino-substituted cyclam. The Co(III) complexes of these three receptors have been prepared and characterized spectroscopically and structurally. Crystal structures of each receptor in complex with an alkali metal ion and structures of the benzo-12-crown-4 and benzo-15-crown-5-receptors without guest ions are reported. 2D NMR and molecular mechanics modeling have been used to examine conformational variations upon guest ion complexation. Addition of cations to these receptors results in an appreciable anodic shift in the Co(III/II) redox potential, even in aqueous solution, but little cation selectivity is observed. Evidence for complex formation has been corroborated by (23)Na and (7)Li NMR spectroscopy and electrospray mass spectrometry.     

Synthesis of oligopyridines and their metal complexes as precursors to topological stereoisomers

[structure: see text]. Palladium-based carbon-carbon coupling reactions in sequence with halogen-exchange chemistry on a series of heterocycles lead to an efficient synthetic strategy for oligopyridines that bind metal ions such as ruthenium to form coordination racks. The particular structures are designed to form terpyridine subunits for octahedral binding. Reaction of 4,6-diiodopyrimidine produces a "double-bay" terpyridine from which binuclear coordination complexes have been formed.     

Metal Vector Manipulated Molecular Self-Assembly from Werner System to Cotton System

A definition of metal vector was given to coordinatively unsaturated metals or asymmetrically coordinated metal complexes in which the metal center is partly blocked by inert chelating ligand(s), thus possess specific reactivity and directionality, such as cis-coordinated square Pd(Ⅱ) or Pt(Ⅱ) complexes. Metal vectors have been extensively used in coordination catalysis and molecular assembly. In 1990, Fujita [ 1 ] first demonstrated the utility of cis-coordinated square Pd(Ⅱ)or Pt(Ⅱ) complexes as a right angular 2D metal vector in the formation of molecular square, a cyclic tetramer with nano-cavity and unique molecular recognition. So far, much attention has been paid to the use of the mononuclear coordination centers (Werner-type metal vectors) in molecular assembly.As late as 1999, Cotton et al. [2] reported the use of cis-coordinated metal-metal bonded dimetal units (Cotton-type metal vectors) to direct assembly of molecular squares.This presentation includes two parts: 1) Werner-type metal vector directed molecular assembly; [3]2) Cotton-type metal vector directed molecular assembly.[4]Firstly, the Werner-type metal vector, cis-coordinated Pd(Ⅱ) nitrate, was used to direct a 6-component self-assembly. This leads to the formation of a molecular bowl or crown with syn,syn,syn conformation. These structures are analogues of calix[3]arenes and can function as anion receptors. Interestingly, an nitrate is found to distort from a trigonal plane into a trigonal pyramid when binding to the bottom of the molecular bowl.Secondly, the Cotton-type metal vector, cis-diRh(Ⅱ, Ⅱ), was used to assemble di- or poly-carboxylate anions into neutral supermolecules. Most interestingly, a calixarene-based carceplex with four cis-diRh(Ⅱ, Ⅱ) fastners was obtained[5].All self-assembling entities were studied by both X-ray crystallographic analysis and solution NMR spectra, which are consistent with the presence of assembling structures even in solution.     

Synthesis and in solution and solid state structural study of intramolecular Pt...H interactions in pentafluorophenyl platinum(II) complexes containing the ligands triazene, formamidine, and 2-aminopyridine

The preparation of the [NBu4][Pt(C6F5)3L] complexes (L=triazene, formamidine, 2-aminopyridine,) have been carried out. These ligands contain a hydrogen atom, with more or less acidic character, in a position suitable for establishing an intramolecular hydrogen bonding interaction with the metal center. This interaction has been detected in solution for; its 1H NMR spectrum shows that the resonance assignable to this hydrogen has platinum satellites. For, this coupling is not observed, and the interaction, if it exists, has to be weaker because of the less acidic character of the hydrogen atom. The 2-aminopyridine ligand is more flexible than the triazene or formamidine, and also in this case, no evidence of the interaction in solution is obtained. Nevertheless, if another potential proton acceptor is present, such as ClO4- in [NBu4]2[Pt(C6F5)3(C5H6N2)](ClO4), a conventional N-H...O-Cl hydrogen bond is formed. The crystal structures of complexes have been determined by X-ray diffraction.     

Intrinsic dinitrogen activation at bare metal atoms

There is ongoing interest in metal complexes which bind dinitrogen and facilitate either its reduction or oxidation under mild conditions. In nature, the enzyme nitrogenase catalyzes this process, and dinitrogen fixation occurs under mild and ambient conditions at a metal-sulfur cluster in the center of the MoFe protein, but the mechanism of this process remains largely unknown. In the last few years, new important discoveries have been made in this field. In this review are discussed recent findings on the interaction of N(2) with metal atoms and metal-atom dimers from all groups of the periodic table as provided by gas-phase as well as matrix-isolation experiments. Intrinsic dinitrogen activation at such bare metal atoms is then related to corresponding processes at complexes, clusters, and surfaces.     

Complete assignments of NMR data of salens and their cobalt (III) complexes

Salens, derived from 1,2‐ethylenediamine and salicylaldehydes, have been widely used as ligands for metal complexes which have been showing enormous potential in chemical properties of asymmetric catalysts as well as biological properties such as anticancer agents. Almost all of the salen–metal complexes with their corresponding metal (II)‐complexes show the evidences of chelation of two oxygens in salens. However, several metal (II) complexes, especially cobalt (II) complexes, could not show NMR spectra due to their paramagnetism. Recently, it has been reported that one of the cobalt (III) complexes was used for NMR spectroscopy to evaluate its stereoselectivity as a catalyst. Even though many salen ligands are known, their NMR data are not assigned completely. It was possible that modification in northern part of salen with 2‐hydroxyphenyl group afforded another oxygen chelation site in salen ligand. Here we report that synthesis and full NMR assignment of new salen ligands, which form meso 1,2‐bis(2‐hydroxyphenyl)ethylenediamine) and their cobalt (III) complexes. The assignments of ¹H and ¹³C NMR data obtained in this experiment can help us to predict the NMR data of other salen ligands. Copyright © 2008 John Wiley & Sons, Ltd.     

Dithiolene complexes containing N coordinating groups and corresponding tetrathiafulvalene donors

The chemistry of transition metal dithiolene complexes containing N coordinating groups and the corresponding TTF donors, is reviewed starting from the ligand synthesis to the coordination structures where these dithiolene complexes are used as bridging units. The dithiolene ligands containing N coordinating atoms present two coordination poles which can selectively bind different metals and act as bridging units in a variety of coordination architectures. The transition metal dithiolene complexes based on these N containing ligands and the corresponding TTF donors can be themselves regarded as ligands. These can be used to coordinate other metals, potentially leading to a diversity of hetero metallic coordination architectures. With the use of appropriate auxiliary ligands they can lead to discrete metal complexes. In addition they can lead to more extended polymeric structures of different dimensionality such as 1D chains, 2D layers or even 3D polymers can also be obtained.