Preparations and applications of synthetic linked azamacrocycle ligands and complexes

Covalently linked azamacrocycles have been known for several decades, but only a modest number of these ligands and their complexes had been described prior to 2000. Since that time, a number of new synthetic methods for their preparation have been discovered, yielding a growing collection of these interesting ligands. Additionally, the number of uses to which these ligands and their metal complexes have been applied has expanded. In this review, the important synthetic methods yielding linked azamacrocycles will be outlined, and their applications will be discussed.     

Ladderane Natural Products: From the Ground Up

The ladderane family of natural products are well known for their linearly concatenated cyclobutane skeletal structure. Owing to their unique carbocyclic framework, several chemical syntheses have been reported since their discovery in 2002. The focus of this review is to showcase the novel tactics that have been used to generate the ladderane core and the challenges that are associated with the synthesis of these unusual and complex natural products.     

Substituents effects on two related families of dyes for dye sensitized solar cells: [Ru(4,4'-R,R-2,2'-bpy)(3)]2+ and [Ru(4,4'-COOH-2,2'-bpy)(4,4'-R,R-2,2'-bpy)(2)]2+

We studied the influence of the substituents over the composition of the molecular orbitals, electronic transitions, and reactivity of several ruthenium derivatives. We found a good agreement with the previously reported experimental data. In these theoretical calculations including spin-orbit coupling, we study several ruthenium-tris-(2,2'-bipyridine) substituted dyes, which do or do not have an anchoring group to get attached to the semiconductor surface. It was observed that the complexes that have electron-donor substituents might be more efficient to donate electrons if they are anchored to a semiconductor than those complexes that have electron-acceptor substituents. Therefore, the results suggest that these dyes with electron-donor substituents will give better yields in photocurrent generation. Also, the localization of the lowest unoccupied molecular orbital over the ligand that has the anchoring will help to improve electron injections into the TiO(2) nanoparticles. We propose here several not yet synthetized dyes, which could be used in this kind of device, due to their interesting molecular properties.     

Enzyme Encapsulation by a Ferritin Cage

Ferritins, conserved across all kingdoms of life, are protein nanocages that evolved to mineralize iron. The last several decades have shown that these cages have considerable technological and medical potential owing to their stability and tolerance to modification, as well as their ability to template nanoparticle synthesis and incorporate small molecules. Here we show that it is possible to encapsulate proteins in a ferritin cage by exploiting electrostatic interactions with its negatively charged interior. Positively supercharged green fluorescent protein is efficiently taken up by Archaeoglobus fulgidus ferritin in a tunable fashion. Moreover, several enzymes were readily incorporated when genetically tethered to this fluorescent protein. These fusion proteins retained high catalytic activity and showed increased tolerance to proteolysis and heat. Equipping ferritins with enzymatic activity paves the way for many new nanotechnological and pharmacological applications.     

Plant Flavonoids: Chemical Characteristics and Biological Activity

In recent years, more attention has been paid to natural sources of antioxidants. Flavonoids are natural substances synthesized in several parts of plants that exhibit a high antioxidant capacity. They are a large family, presenting several classes based on their basic structure. Flavonoids have the ability to control the accumulation of reactive oxygen species (ROS) via scavenger ROS when they are formed. Therefore, these antioxidant compounds have an important role in plant stress tolerance and a high relevance in human health, mainly due to their anti-inflammatory and antimicrobial properties. In addition, flavonoids have several applications in the food industry as preservatives, pigments, and antioxidants, as well as in other industries such as cosmetics and pharmaceuticals. However, flavonoids application for industrial purposes implies extraction processes with high purity and quality. Several methodologies have been developed aimed at increasing flavonoid extraction yield and being environmentally friendly. This review presents the most abundant natural flavonoids, their structure and chemical characteristics, extraction methods, and biological activity.     

Trends in nanomaterial-based solid-phase microextraction with a focus on environmental applications - A review

Effective solid-phase microextraction (SPME) in environmental field represents a crucial step for the adequate extraction of several analytes. Several materials have been traditionally developed for SPME of several analytes from environmental samples, even though their several restrictions such as post-treatment required, elevate costs and limited efficiency. Recently, nanomaterials (NMs) have emerged as a promising substitute for SPME in environmental applications of traditional techniques, due to their small size and their high specific surface-area which enhances their high reactivity. In this present review different NMs which have recently been utilized as SPME sorbent for environmental applications are classified into eleven main groups, namely nanoparticles, nanofibers, nanoflakes, nanocomposites, nanorods, nanotubes, nanohorns, nanosheets, nanocubes, nanospheres and polymer-based NMs. Application of these NMs in SPME modes and configurations for environmental analysis has been reviewed. The study discusses not only the advantages but also the major limitations of using such NMs.     

The sorbicillinoid family of natural products: isolation, biosynthesis, and synthetic studies

The sorbicillinoids are a family of hexaketide metabolites that have been isolated from a variety of fungal sources, collected from both marine and terrestrial sources. Since 1948, the family has grown in size to include over 50 members, many of which have complex, highly oxygenated, bicyclic and tricyclic frameworks. In conjunction with their biological activity, the structural complexity of these structures has inspired several synthetic campaigns and has also led to controversy surrounding the biosynthetic pathway responsible for the natural production of these compounds. Through this review, we aim to give a historical perspective to each of these areas and hope to inspire new avenues of research for addressing the knowledge gaps that still exist.     

Artemisinin and Derivatives-Based Hybrid Compounds: Promising Therapeutics for the Treatment of Cancer and Malaria

Cancer and malaria are major health conditions around the world despite many strategies and therapeutics available for their treatment. The most used strategy for the treatment of these diseases is the administration of therapeutic drugs, which suffer from several shortcomings. Some of the pharmacological limitations associated with these drugs are multi-drug resistance, drug toxicity, poor biocompatibility and bioavailability, and poor water solubility. The currently ongoing preclinical studies have demonstrated that combination therapy is a potent approach that can overcome some of the aforementioned limitations. Artemisinin and its derivatives have been reported to exhibit potent efficacy as anticancer and antimalarial agents. This review reports hybrid compounds containing artemisinin scaffolds and their derivatives with promising therapeutic effects for the treatment of cancer and malaria.     

Structure-fluorescence contrast relationship in cyanine DNA intercalators: toward rational dye design

The fluorescence enhancement mechanisms of a series of DNA stains of the oxazole yellow (YO) family have been investigated in detail using steady-state and ultrafast time-resolved fluorescence spectroscopy. The strong increase in the fluorescence quantum yield of these dyes upon DNA binding is shown to originate from the inhibition of two distinct processes: 1) isomerisation through large-amplitude motion that non-radiatively deactivates the excited state within a few picoseconds and 2) formation of weakly emitting H-dimers. As the H-dimers are not totally non-fluorescent, their formation is less efficient than isomerisation as a fluorescent contrast mechanism. The propensity of the dyes to form H-dimers and thus to reduce their fluorescence contrast upon DNA binding is shown to depend on several of their structural parameters, such as their monomeric (YO) or homodimeric (YOYO) nature, their substitution and their electric charge. Moreover, these parameters also have a substantial influence on the affinity of the dyes for DNA and on the ensuing sensitivity for DNA detection. The results give new insight into the development and optimisation of fluorescent DNA probes with the highest contrast.     

ABSORPTION AND EMISSION STUDIES OF ELECTRONIC STATES OF N-ARYLBENZAMIDES

Abstract— Absorption and emission spectra of several N-arylbenzamides have been measured. The quantum yields for their fluorescence were found to be dependent on matrix viscosity and temperature. Singlet-triplet splittings for these compounds were determined from their emission spectra and found to be abnormally small for π. π* states (˜ 1500 cm^-1). Indeed, the phosphorescence maxima of N-arylbenzamides occur slightly to the blue relative to their fluorescence maxima. Intersystem crossing efficiencies were determined for several of these compounds and are consistent with S₁→ S ₀ radiationless decay.     

Design, synthesis, and structure--activity relationships for chimeric inhibitors of Hsp90

Inhibition of the 90 kDa heat shock protein (Hsp90) family of molecular chaperones represents a promising new chemotherapeutic approach toward the treatment of several cancers. Previous studies have demonstrated that the natural products, radicicol and geldanamycin, are potent inhibitors of the Hsp90 N-terminal ATP binding site. The cocrystal structures of these molecules bound to Hsp90 have been determined, and through molecular modeling and superimposition of these ligands, hybrids of radicicol and geldanamycin have been designed. A series of macrocylic chimeras of radicicol and geldanamycin and the corresponding seco-agents have been prepared and evaluated for both antiproliferative activity and their ability to induce Hsp90-dependent client protein degradation.     

TAT peptide internalization: seeking the mechanism of entry

During the last decade several peptides have been extensively studied for their ability to translocate across the plasma membrane. These peptides have been called "cell penetrating peptides" (CPP) or "protein transduction domains" (PTD). These peptides also promote the cellular uptake of various cargo molecules. Their mechanism of cellular entry appeared very intriguing since most publications in the field highlighted an energy-independent process. Indeed, cellular uptake of these peptides was still observed by fluorescence microscopy at low temperature or in the presence of several drugs known to inhibit active transport. In addition, internalization was reported to be much faster than known endocytic processes. However the involvement of a specific cellular component responsible for this uptake process appeared unlikely following intensive structure activity relationship studies using a wide panel of Tat analogues. Several reports about a possible artefactual redistribution of CPPs, and their associated cargos, during the cell fixation step commonly used for fluorescence microscopy have recently emerged in the literature. Moreover strong ionic interactions of CPPs with the cell surface also led to an overestimation of the recorded cell-associated fluorescent signal. It now seems well established that arginine-rich peptides are internalized by an energy dependent process involving endocytosis. Whatever the case, however, an increasing number of data indicate that the conjugation of non-permeant molecules to these CPPs allows their cellular uptake and leads to the expected biological responses, thus pointing to the interest of this delivery strategy. However, initial structure activity relationship studies of these CPPs will have to be reconsidered and the relative potency of each peptide (and their analogues) to vectorize the cargos to their most appropriate subcellular compartment will require careful re-evaluation.     

Pyridine based zirconium(IV) and tin(IV) phosphates as new and novel intercalated ion exchangers

Pyridine based zirconium(IV) phosphate (PyZrP) and tin(IV) phosphate (PySnP) have been synthesized as new and novel intercalated ion exchangers. These materials have been characterized using X-ray, IR spectra, TG, DTG and DTA studies in addition to their ion exchange capacity, elution, pH titration, concentration and distribution behaviour. The distribution studies towards several metal ions in different media/concentrations have suggested that PyZrP and PySnP are selective for Hg(II) and Pb(II), respectively. As a consequence some binary separations of metal ions involving Hg(II) and Pb(II) ions have been performed on a column of these materials, demonstrating their analytical and environmental potential.     

Combinatorial chemistry toward understanding the function(s) of carbohydrates and carbohydrate conjugates

Combinatorial chemistry has contributed significantly to understanding the structure-function relationships of biologically important molecules such as proteins and nucleic acids. However, carbohydrates and carbohydrate conjugates, which have been identified as key modulators of several biological functions have not enjoyed the same measure of success. The complexity and synthetic challenges of carbohydrate conjugates have resulted in a number of conceptual approaches to rapidly access sufficient quantities of these biomolecules. This article summarizes these combinatorial approaches and also highlights fully automated library synthesis of artificial glycopeptides with the goals of understanding their biological roles.     

Computational simulation of the molecular structure and properties of heterocyclic organic compounds with possible corrosion inhibition properties

The damages by corrosion generate not only high costs for inspection, repairing and replacement, but in addition these constitute a public risk. Thus the necessity of developing novel substances that behave like corrosion inhibitors. In general, the organic compounds have demonstrated a great effectiveness in inhibiting the watery corrosion of many metals and alloys. It has been demonstrated that the compounds that have nitrogen and sulfur in their structure provide a greater inhibition than those than only contain one of the atoms at a time, being this property attributable to its molecular structure. The objective of this work is to provide information about the electronic and molecular structure of several heterocyclic organic compounds: 1,3,4-thiadiazole and its derivatives, with different nucleophilic and electrophilic alkyl substituents (R1 and R2), obtained through quantum-chemistry calculations conducted by means of the gaussian 03W set of programs. It is an attempt to find the correlation between the molecular structure of these compounds and their possible behavior like corrosion inhibitors. It is important to take into account the effect of films formed by products of corrosion. Thus, the incorporation of metallic atoms in the calculations provides greater information about the relation between the reactivity of compounds and the metallic surface, in addition to the formation of stable complexes. The behavior of these organic substances in the presence of several solvents, among them water, facilitates the understanding of the processes of inhibition of the corrosion.     

Separation of structural,geometrical and optical isomers of epoxycarotenoids using triacontyl‐bonded stationary phases

The efficiency of C₃₀ stationary phases in the separation of carotenes and diverse hydroxycarotenoids has been the subject of several studies. However, little is known concerning their ability to resolve epoxycarotenoids isomers, whose study is of great importance due to the functions they serve and the information they can reveal concerning the processing of foods. We have concluded that C₃₀ columns provide an excellent separation of structural, geometrical and optical isomers of epoxycarotenoids and that the presence of 5,8‐epoxide groups leads to a better shape recognition, to the extent that over 10 geometrical–optical isomers of 5,8‐epoxycarotenoids have been separated. Additionally, it was observed that these carotenoids elute later than their 5,6‐epoxide counterparts, albeit the latter have a longer chromophore.     

A study of hydration effects on the conformational aspects of gaba mediators

The conformation of numerous chemical compounds is strongly influenced by solvents. Knowledge of their structure in solution is necessary, especially for a discussion of the biological and pharmacological activity of the molecules. The neurotransmitters and their agonists and antagonists are known to be flexible molecules that interact with quite distinct receptors. The conformational properties of several GABA (γ-aminobutyric acid) mediators have been studied by the MNDO technique. The optimized geometries of the molecules have been used to study the solvent effects on their conformational properties considering the supermolecule approach for their first hydration shell. A conjectural pharmacophoric pattern for several GABA inhibitors has already been suggested from the molecular electrostatic potentials (MEP ) of several molecules using a localized bond orbital technique. In the present work, MEP calculations have been carried out considering a solvent effect on the MNDO optimized geometries to investigate any deviation from the earlier results.     

Selective binding of two-armed diketopiperazine receptors to side-chain-protected peptides

The binding properties of two-armed receptors based on a diketopiperazine template toward side-chain-protected peptides have been elucidated. Selective binding of these diketopiperazine receptors is not limited to side-chain-free peptides, but combinatorial on-bead assays show that also side-chain-protected peptides are recognized with high specificity. Furthermore, the screening of several dye-marked diketopiperazine receptors against an encoded side-chain-protected tripeptide library demonstrated not only their high binding specificities but also revealed that small structural changes suffice to alter the binding preferences significantly.     

Aspartic proteinase content of the Arabidopsis genome

The sequence of the Arabidopsis genome has given us information about one plant's complement of aspartic proteinases. Using an in silico analysis based on the homology to known aspartic proteinase genes, we have uncovered 51 sequences that potentially encode these enzymes. This is substantial more than the number predicted for other eukaryotic systems. We have grouped the deduced amino acid sequences into 3 classes - typical plant aspartic proteinase, nucellin-like and atypical aspartic proteinase sequences-, depending on their putative domain organizations and their active site sequence motifs. Searching databases has revealed cDNAs or ESTs for nearly 90% of these genes. Sequence analysis using software that detects targeting signals indicates most of the predicted proteins have the expected localization in the secretory system although several of these are membrane bound. The analysis also predicts 8 chloroplast localized proteins and 2 mitochondria-localized aspartic proteinase-like proteins. The wide variety of structures and subcellular locations implies multiple functions for aspartic proteinases in plants.