Lower-Rim Substituted Calixarenes and Their Applications

This review discusses in detail “calixarenes” since their discovery as by-products of the phenol formaldehyde bakelites till the present scenario wherein calixarene has assumed a new dimension in the field of supramolecular chemistry. Extensive literature exists for calixarenes; but herein we have tried to concentrate on the different lower-rim modified calixarenes with their potential applications. An attempt has also been made to critically evaluate the synthesis procedures for different lower-rim substituted calixarenes

Methods of producing singlet oxygen using compounds having improved functionalization

Novel texaphyrin compounds having improved functionalization are described. Metal complexes of these compounds are active as photosensitizers for the generation of singlet oxygen and thus are potentially useful for treatments performed with singlet oxygen. Several of the metallotexaphyrin complexes absorb light in the physiologically important range of 690-880 nm. The complexes form long-lived triplet states and thus may act as efficient photosensitizers for generation of singlet oxygen.Board of Regents, University of Texas Syste

Advances in anion supramolecular chemistry:from recognition to chemical applications

Since the start of this millennium, remarkable progress in the binding and sensing of anions has been taking place, driven in part by discoveries in the use of hydrogen bonding, as well as the previously under-exploited anion–π interactions and halogen bonding. However, anion supramolecular chemistry has developed substantially beyond anion recognition, and now encompasses a diverse range of disciplines. Dramatic advance has been made in the anion-templated synthesis of macrocycles and interlocked molecular architectures, while the study of transmembrane anion transporters has flourished from almost nothing into a rapidly maturing field of research. The supramolecular chemistry of anions has also found real practical use in a variety of applications such as catalysis, ion extraction, and the use of anions as stimuli for responsive chemical systems

Method of magnetic resonance image enhancement

Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O.sub.2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.Board of Regents, University of Texas Syste

Water soluble texaphyrin metal complexes for enhancing relaxivity

The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.Board of Regents, University of Texas Syste

Functional polymers: polyoxanorbornene-based block copolymers for the separation of f-elements and luminescent conducting metallopolymers

A new polymeric material with a polyoxanorbornene backbone and carbamoylmethylphosphine oxide, CMPO, ligand pendant groups has been synthesized, characterized, and studied. The ability of the material to selectively partition actinides utilizing a biphasic extraction strategy was tested. The polymeric materials had significantly higher (> 5-25 times) ability to extract Th4+ than the monomeric system. The molecular weight of the material affected the extraction and separation abilities. The lower molecular weight material extracted more ions, but was less discriminate for thorium(IV) over cerium(III), lanthanum(III), and europium(III), than the higher molecular weight material. Structural modifications to this system were made by creating block copolymers. The influence of additional functionalities, created by the addition of new polymeric blocks, was investigated. The ability of the material to selectively partition actinides utilizing both solid-liquid and liquid-liquid extraction strategies was tested. Extraction efficiencies comparable to liquid-liquid extractions were achieved in the solid-liquid extractions. The extraction behavior of the materials was significantly altered by the incorporation of new blocks. The incorporation of glycol chains into the system caused an increase in the uptake of thorium(IV) over the homopolymers. The incorporation of blocks of glycol chains and blocks of cross-linked hydroxcoumarian increased the selectivity significantly (XTh/Eu 2.3 – 4.5 times higher) over the homopolymer. These materials show tremendous promise as modular polymeric scaffolds. A novel emissive tetradentate platinum complex with electropolymerizable ethylenedioxythiophene groups has been synthesized and characterized. This material has been developed for use as the active layer in polymer light-emitting diodes. Electropolymerization offers ease of processing by depositing thin films directly onto an electrode during the polymerization process. Additionally because the emitter is covalently bound in the polymer, it cannot aggregate as is the case with some small molecule emitters. The platinum complex displayed emission peaks at 510 nm and 544 nm. Electropolymerization resulted in a conductive and emissive thin film, with an emission maximum at 453 nm.Chemistr

Salen and Related Ligands

The salen and related ligands are very popular among the inorganic chemists due to multiple reasons such as ease in synthesis, coordinating ability with very long range of metal ions, facilitating the metal ions to adopt various geometries, ability of stabilising the metal ion in variable oxidation states and potential applications of metallosalen in several fields. The most common application of metallosalen is in the field of catalysis because of their recoverability, reusability, high efficiency, high selectivity and their capability of working as homogeneous as well as heterogeneous catalysts for numerous functional group manipulations including asymmetric synthesis. Molecular magnetism, sensory applications, bioinorganic activities and medicinal applications of metallosalen are also very promising areas of their applications. Porous materials involving metal organic frameworks (MOFs) and supramolecular building blocks are increasingly getting attention of researchers for the gas absorption and heterogeneous catalysis

Water soluble texaphyrin metal complex preparation

The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of enveloped viruses, mononuclear or other cells infected with such viruses as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.Board of Regents, University of Texas Syste

Paramagnetic NMR Spectroscopy for Investigating Protein Structure and Dynamics

Paramagnetic NMR spectroscopy is an indispensable tool in the study of biomolecules, especially proteins. In addition to providing structural information, it allows the study of structural dynamics, protein-protein and protein-ligand interactions at atomic resolution, under conditions similar or identical to the physiological environment. This thesis focuses on i) the development of new labels and probes to improve the sensitivity, resolution and the scope of NMR spectroscopy of biomolecules and ii) the application of this technique to study proteins with clinical importance. Chapter 2 describes a novel chiral lanthanide binding tag referred to as C12 tag, which is based on a stable cyclen complex. It reacts spontaneously with a cysteine residue of a protein to generate a stable thioether bond. It also opens a route towards selective tagging of selenocysteine in proteins containing cysteine residues, due to its greatly enhanced reactivity towards selenocysteine. This tag readily generates PCSs in protein NMR spectra when loaded with paramagnetic metal ions. The relatively rigid aromatic tether it produces between the lanthanide and the protein is beneficial for interpretation of the PCSs by single magnetic susceptibility anisotropy tensors. Moreover, this tag is suitable for measuring distance distributions in double electron-electron resonance experiments and as a highly sensitive turn-on luminescence probe for time-resolved FRET assays and enzyme reaction monitoring. Chapter 3 describes the incorporation of 13C/19F/2H labelled indoles as tryptophan precursors into proteins and their applicability as protein NMR probes. The protocol introduced here for incorporating indoles using cell-free media enables convenient and economical production of proteins with differently labelled tryptophans from the corresponding indoles. By carrying out NMR experiments of labelled indole incorporated T4 lysozyme, it is demonstrated that the exceptional TROSY effect associated with aromatic 19F-13C spin pairs is indeed pronounced for a protein containing fluoro-tryptophans and it is less significant for 1H-13C spin pairs. Perdeuteration of the indole rings causes minor improvement to the 13C NMR spectrum of the protein, hence indicating that 1H decoupling is not important. Moreover, efficient routes are established for the synthesis of indoles with 1H-13C or 19F-13C moieties installed at single sites in the aromatic ring. Chapter 4 describes the incorporation of fluorinated amino acids into proteins utilizing the E. coli cell machinery. 3-fluoro-alanine is an amino acid of interest for protein NMR due to the large coupling constant of fluorine to the two geminal protons. Although its toxicity prevents the incorporation in vivo, a protocol is established to incorporate 3-fluoro-alanine into proteins in cell-free media. Its applicability for 1H-19F 2D NMR experiments is also demonstrated. Fluorinated valine and leucine analogues are also incorporated into proteins in cell free media using the natural aminoacyl-tRNA synthetases. Chapter 5 describes an approach to localise the loop lying the active site of the metallo beta lactamase IMP-1. This loop assumes different conformations in single crystal structures. To probe its position in solution the tryptophan residues were labelled with deuterated 7-13C- indole and lanthanoid tags were incorporated at three different sites of the protein. The atomic coordinates of the tryptophan side chains in the protein were determined using magnetic susceptibility anisotropy tensors. The localization spaces defined by the tryptophan PCSs fully agreed with the crystal structures of IMP-1 for all tryptophan residues. The result showed a little change of the average conformation of the loop upon binding of the inhibitor, captopril. Chapter 6 describes an approach to study the conformational changes of an intermediate messenger protein, calmodulin upon binding of its substrate, MARCKS peptide