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Calixarenes, along with cyclodextrins (viz. β-CD) and crown ethers, are the most commonly studied macrocyclic compounds. These bucket shaped molecules have gained tremendous importance for having both hydrophilic and hydrophobic compartments together in the same species. The primary target of this review is to give the readers of various disciplines an updated overview of the recent advancements of the conjugates of calixarenes with respect to their nano chemistry in understanding the nanoscience of these supramolecular systems. Calixarenes now compete with cyclodextrins and calixresorcinols. Thus it is important to look into the current advancement in the literature to draw appropriate comparisons and to provide appropriate designs for their nano science aspects. This review is expected to provide all this. The review covers over 113 conjugates of calixarenes published in 106 references that include contributions from our research group. All the conjugates and their nanoscience aspects were depicted through 63 figures and two schemes. The characterization of these nano systems has been carried out by a variety of techniques that includes spectroscopy and microscopy. The advancement of the conjugates of calixarenes in the nanoworld can be considered as one of the most recent encroachment in the calixarene chemistry and is expected to come out as a major thrust research area in near future.

Amide linked lower rim 1,3-dibenzimidazole derivative of calix[4]arene, L has been shown to be sensitive and selective to Hg(2+) in aqueous acetonitrile solution based on fluorescence spectroscopy, and the stoichiometry of the complexed species has been found to be 1:1. The selectivity of L toward Hg(2+) has been shown among 11 M(2+) ions, viz., Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), Ca(2+), and Mg(2+) studied, including those of the mercury group and none of these ions impede the recognition of Hg(2+) by L. Role of the solvent on the recognition of Hg(2+) has been demonstrated. The role of calix[4]arene platform and the benzimidazole moieties in the recognition of Hg(2+) by L has been delineated upon performing such studies with five different molecules of relevance as reference molecular systems. The binding cores formed by the receptor L and the reference compounds have been established based on the single crystal XRD structures, and the preferential metal ion binding cores have been discussed. The binding of Hg(2+) with L has been further established based on (1)H and (13)C NMR, ESI MS, absorption, and fluorescence lifetime measurements. Some of these techniques have been used to establish the stoichiometry of the species formed. The complex species formed between L and Hg(2+) have been isolated and characterized and found to be 1:1 species even in the isolated complex. Whereas transmission electron microscopy (TEM), atomic force microscopy (AFM), and scanning electron microscopy (SEM) provided the nanostructural behavior of L, the TEM and SEM demonstrated that the mercury complex has different characteristics when compared to L. The TEM, SEM, and powder XRD studies revealed that whereas L is crystalline, that of the mercury complex is not, perhaps a reason for not being able to obtain single crystals of the complex. Binding characteristics of Hg(2+) toward L have been established based on the DFT computational calculations.

The detection of pesticide residues in ground water, food, or soil samples is extremely important. The currently available laboratory techniques have several drawbacks and needs to be replaced. Fluorescent chemosensors for pesticide detection were reported in the literature, with few reports published on quantum dot-based pesticide sensors, but none of these were focused toward differentiating organophosphorus and organochlorine pesticides specifically. In this respect, glutathione-coated CdS nanoparticles were synthesized and characterized. The TEM studies of the nanoparticles suggested mostly monodispersed spherical particles, with size in the range of 11.5±1 nm. The prepared fluorescent nanoparticles were found to selectively recognize organochlorine pesticide dicofol among all the other pesticides studied, by increasing the fluorescence intensity of the nanoparticles ~ 2.5 times. Similar studies carried out with organophosphorous pesticide dimethoate did not result any change in the fluorescence intensity of the nanoparticles. Further studies carried out with commercially available pesticide solutions, also confirmed similar results. The TEM, SEM, and DLS studies suggested aggregation of the nanoparticles in the presence of dicofol. Control experiments suggested possible role of both amine and carboxylic acid functional groups of glutathione in the recognition of dicofol. The limit of detection of dicofol was found to be ~ 55±11 ppb. Glutathione-coated CdS nanoparticles selectively recognize organochlorine pesticide dicofol among all the other pesticides studied, by increasing the fluorescence intensity of the nanoparticles. The TEM, SEM, and DLS studies suggested aggregation of the nanoparticles in the presence of dicofol.

The quest for design of newer/advanced methods for medical diagnosis and targeted therapeutics are of utmost interest and challenging too, because of its importance in clinical diagnosis. Currently available diagnosis methodologies have their own disadvantages. These shortcomings can be overcome by using multimodal imaging systems where two or more imaging modalities may be coupled. Nanoparticles being widely studied for targeted drug delivery and as biological contrasting agents, might play a decisive role in such findings. This review is focused towards the ongoing research in the area of hybrid nanocomposites which can be used for both as MRI contrasting agent (magnetic nanoparticles) and molecular imaging studies (using fluorescent quantum dots) at in vitro and in vivo level. Though several reports are available in literature for such bimodal imaging systems, their clinical trials are very restricted, possibly because of the lack of communication between the in vitro and in vivo studies. This review is expected to bridge the gap between such studies.

A multifunctional hybrid nanocomposite material of iron oxide nanoparticles and CdS quantum dots was synthesized by a direct amide coupling reaction. The prepared nanoparticles were characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and zeta potential studies. The TEM studies suggested that the sizes of the particles were in the range of 13.5 ± 1 nm. The energy dispersive x-ray (EDX) analysis confirmed the presence of Fe, Cd and S in the nanocomposites. To check the utility of this nanocomposite as a molecular imaging probe, these nanoparticles were further conjugated with folic acid. The folic acid conjugated nanocomposites were treated with rat glioma cells (C6, folic acid receptor over-expressing cell lines), human lung adenocarcinoma epithelial cells (A549, folic acid receptor negative cell lines) and normal mouse splenocytes for cell uptake and cytotoxicity studies. The nanoparticle internalization to C6 cells was confirmed by green fluorescence emission from these cells. Prussian blue staining studies suggested the intracellular presence of iron oxide. Further it was found that folic acid conjugated nanocomposites were significantly toxic to C6 cells only after 48 h but not to A549 cells or splenocytes. These studies indicated that the prepared nanocomposites have the potential to be used as delivery agent for magnetic and fluorescent materials towards folic acid receptor over-expressing cells and thus can find their application in the field of in vitro imaging diagnosis.

Lower rim 1,3-diamido conjugates of calix[4]arene have been synthesized and characterized, and the structures of some of these have been established by single crystal XRD. The amido-calix conjugates possessing a terminal -COOH moiety have been shown to exhibit recognition toward guest molecules possessing -COOH moiety, viz., Asp, Glu, and reduced and oxidized glutathione (GSH, GSSG), by switch-on fluorescence in aqueous acetonitrile and methanol solutions when compared to the control molecules via forming a 1:1 complex. The complex formed has been shown by mass spectrometry, and the structural features of the complexes were derived on the basis of DFT computations. The association constants observed for the recognition of Asp/Glu by Phe-calix conjugate, viz., 532/676 M(-1), are higher than that reported for the recognition of Val, Leu, Phe, His, and Trp (16-63 M(-1)) by a water-soluble calixarene (Arena, G., et al. Tetrahedron Lett. 1999, 40, 1597). For this recognition, there should be a free -COOH moiety from the guest molecule. AFM, SEM, and DLS data exhibited spherical particles with a hundred-fold reduction in the size of the complexes when compared to the particles of the precursors. These spherical particles have been computationally modeled to possess hexameric species reminiscent of the hexameric micellar structures shown for a Ag(+) complex of a calix[6]arene reported in the literature (Houmadi, S., et al. Langmuir 2007, 23, 4849). Both AFM and TEM studies demonstrated the formation of nanospheres in the case of GSH-capped Ag nanoparticles in interaction with the amido-calix conjugate that possesses terminal -COOH moiety. The AFM studies demonstrated in this paper have been very well applied to albumin proteins to differentiate the aggregational behavior and nanostructural features exhibited by the complexes of proteins from those of the uncomplexed ones. To our knowledge, this is the first report wherein a amido-calix[4]arene conjugate and its amino acid/peptide/protein complexes have been differentiated on the basis of spectroscopy and microscopy studies followed by species modeling by computations.

This paper deals with the self-assembly of the 1:1 complex of two different amphiphiles, namely, a glucosyl-salicyl-imino conjugate (L) and phenylalanine (Phe), forming nanofibers over a period of time through pi...pi interactions. Significant enhancement observed in the fluorescence intensity of L at approximately 423 nm band and the significant decrease observed in the absorbance of the approximately 215 nm band are some characteristics of this self-assembly. Matrix-assisted laser desorption ionization/time of flight titration carried out at different time intervals supports the formation of higher aggregates. Atomic force microscopy (AFM), transmission electron microscopy, and scanning electron miscroscopy results showed the formation of nanofibers for the solutions of L with phenylalanine. In dynamic light scattering measurements, the distribution of the particles extends to a higher diameter range over time, indicating a slow kinetic process of assembly. Similar spectral and microscopy studies carried out with the control molecules support the role of the amino acid moiety over the simple -COOH moiety as well as the side chain phenyl moiety in association with the amino acid, in the formation of these fibers. All these observations support the presence of pi...pi interactions between the initially formed 1:1 complexes leading to the fiber formation. The aggregation of 1:1 complexes leading to fibers followed by the formation of bundles has been modeled by molecular mechanics studies. Thus the fiber formation with L is limited to phenylalanine and not to any other naturally occurring amino acid and hence a polymer composed of two different biocompatible amphiphiles. AFM studies carried out between the fiber forming mixture and proteins resulted in the observation that only BSA selectively adheres to the fiber among the three alpha-helical and two beta-sheet proteins studied and hence may be of use in some medical applications.

A structurally characterized lower rim 1,3-di{bis(2-picolyl)}amide derivative of calix[4]arene (L) exhibits high selectivity toward Ag(+) by Forming it 1:1 complex, among nine other biologically important metal ions, viz., Na(+), K(+), Mg(2+), Ca(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), and Zn(2+), its studied by fluorescence, absorption, and (1)H NMR spectroscopy. The 1:1 complex formed between L and Ag(+) has been further proven on the basis of ESI mass spectrometry and has been shown to have art association constant, K(a), of 11117 +/- 190 M(-1) based on fluorescence data. L acts as it primary ratiometric sensor toward Ag(+) by switch-on fluorescence and exhibits a lowest detectable concentration of 450 ppb. DFT computational studies carried out in mimicking thie formation of a 1:1 complex between L and Ag(+) resulted in it tetrahedral complex wherein the nitrogens of all four pyridyl moieties present on both arms are being coordinated. Whereas these pyridyls are located farther apart in the crystal structure, appropriate dihedral changes are induced in the arms in the presence of silver ion in order to form a coordination complex. Even the nanostructural features obtained in TEM clearly differentiates L from its Ag(+) complex. The in situ prepared silver complex of L detects Cys ratiometrically among the naturally occurring amino acids to a lowest concentration of 514 ppb by releasing L from the complex followed by formation of the cysteine complex of Ag(+). These were demonstrated on the basis of emission,absorption, (1)H NMR,and ESI mass spectra. The INH logic gate has also been generated by choosing Ag(+) and Cys as input and by monitoring the Output signal at 445 nm that originates from the excimer emission of L in the presence of Ag(+). Thus L is a potential primary sensor toward Ag(+) and is it secondary sensor toward Cys.

A lower rim naphthylidene conjugate of calix[4]arene [L] has been synthesized and characterized, and the structure has been established on the basis of single crystal XRD. The L has been found to be selective toward Zn(2+), which induces appropriate changes in the arms of L so that the N(2)O(2) coordination results in the formation of a tetrahedral complex; namely, [ZnL]. [ZnL] recognizes Asp, Cys, His, and Glu from among the naturally occurring amino acids owing to the protonation and chelating ability of the amino acid and the pi-pi interaction ability of the side chain of the amino acid with [ZnL]. All of these features have been demonstrated oil the basis of fluorescence, absorption, and lifetime measurements. The rechelation of Zn(2+) by the amino acid used in the titration has been demonstrated on the basis of ESI-MS studies in the case of Cys to result in a Zn(2+) complex having either 5- or 6-coordination. [ZnL] has also been shown to be selective toward glutathione and glutathione oxidized, The amino acids present in the proteins also interact with [ZnL], resulting in dechelation of [ZnL] as well as aggregation of the protein, as demonstrated on the basis of absorption and fluorescence spectroscopy and atomic force microscopy. The alpha-helical proteins (namely, albumins) exhibit greater conformational changes, as compared to the beta-sheet proteins (namely, lectins), as studied oil the basis of CD spectroscopy, The aggregation of the proteins when treated with [ZnL] follows a trend: peanut agglutinin < bovine serum albumin < jacalin < human serum albumin. The present studies clearly demonstrated the recognition features of [ZnL] toward Asp, Cys, His, and Glu, and the peptides and proteins containing these by spectroscopy and microscopy studies.

A highly selective fluorescence switch on sensor, L for detecting Cu2+ has been synthesized by introducing a bis-(2-picolyl)amine moiety at the lower rim of a calix[4]arene platform via amide linkage. Binding properties of L toward ten different biologically relevant Mn+ ions have been studied by fluorescence and absorption spectroscopy in methanol and aqueous methanol. L was found to detect Cu2+ selectively down to a concentration of 196 and 341 ppb, respectively, in methanol and 1:1 aqueous methanol even in the presence of other metal ions. The composition of the complex has been found to be 1:1 based on the Job plot and is further confirmed by ESI MS. The role of calix[4]arene platform as well as the pre-organized binding core in the selective recognition of Cu2+ has been demonstrated by studying appropriate reference molecules. The possible modes of binding of L with Cu2+ have been modeled by computational calculations. L and its Cu2+ complex could very well be differentiated based on the nano-structural features observed in SEM and AFM., © Elsevier