Rising of a global silent killer: critical analysis of chronic kidney disease of uncertain aetiology (CKDu) worldwide and mitigation steps.

Chronic kidney disease of uncertain aetiology (CKDu) is an advanced version of chronic kidney disease (CKD) which bears a high burden on the world health economy. More than 200 articles were analysed to understand the disease responsible for more than 30,000 deaths per year. CKDu is a non-communicable occupational disease that has a progressive deterioration of the kidney in the absence of CKD risk factors such as hypertension, diabetes and glomerulonephritis, while the diagnosis is only possible at the later stages when kidney function is no longer effective. Published evidence for the existence of CKDu was found for around 35 countries. This is a growing health issue in Asia, Central America, Africa and Middle East with identified hot spots. Despite many research studies over decades, the exact root causes are still uncertain. Six main suspected causative factors are identified. Those are heat stress, strenuous labour, dehydration, use of agrochemicals, exposure to heavy metals and the use of polluted water and agricultural lands. This review summarizes four key areas which are CKDu and its general medical background, worldwide prevalence, suspected causative factors and potential circumventing steps to mitigate against CKDu. The importance of further studies addressing early detection and surveillance methods, contribution of nephrotoxins in environmental health, soil chemistry on transporting nephrotoxins, geological parameters which influence the prevalence of the disease and other related sectors to overcome the mysterious nature is highlighted. Mitigation steps to lessen the burden of CKDu are also identified.

Ionic recognition by 7-nitro-1,3,5-triaza adamantane: first thermodynamic study.

A thermodynamic study involving 7-nitro-1,3,5-triaza adamantane, 1, and its interaction with metal cations in nonaqueous media is first reported. Solubility data of 1 in various solvents were used to derive the standard Gibbs energies of solution, DeltaG(s)o in these solvents. The effect of solvation in the different media was assessed from the Gibbs energy of transfer taking acetonitrile as a reference solvent. 1H NMR studies of the interaction of 1 and metal cations were carried out in CD3CN and CD3OD and the data are reported. Conductance measurements revealed that this ligand forms lead(II) or zinc complexes of 1:1 stoichiometry in acetonitrile. It also revealed a stoichiometry of two molecules of 1 per mercury(II) and two cadmium (II) ions per molecule of 1. The addition of silver salt to 1 led to the precipitation of the silver-1 complex which was isolated and characterized by X-ray crystallography. At variance with conductance measurements in solution, in the solid state the X-ray structure shows a 1:1 stoichiometry in the Hg(II) complex. The thermodynamics of complexation of 1 and these cations provide a quantitative assessment of the selective behavior of this ligand for ions of environmental relevance.

Calix[4]arene urea derivatives: The pathway from fundamental studies to the selective removal of fluorides and phosphates from water.

Wet processes of phosphoric acids produce untreated wastewater containing large amounts of fluoride leading to serious environmental problems. This paper reports fundamental studies on two lower rim functionalised calix[4]arene based receptors namely 5, 11, 17, 23 tetra-tert-butyl, 25, 27 bis [diethylphenylurea]ethoxy, 26, 28 dihydroxycalix[4]arene, 1 and 25, 27 bis[diethylphenylurea]ethoxy, 26, 28 dihydroxycalix[4]arene, 2 and their ionic interactions. It is shown that these receptors only interact with fluoride and phosphate in acetonitrile. Their receptive properties are higher for phosphate (2:1 anion:receptor complex) relative to fluoride (1:1 complex). However, thermodynamics shows that these receptors are more selective for fluoride relative to phosphate in the formation of the 1:1 complex. The pathway from fundamental studies to the use of these receptors for removing these anions from water has been tested. The receptive properties of 1 for phosphate are held when the extraction involves aqueous solutions containing individual ions. However, in mixtures containing both anions, the kinetics of the process and the selectivity of 1 for fluoride predominate and as a result, fluoride is better extracted than phosphate. The counter-ion effect on the removal process is assessed from Molecular Simulation studies. The removal of fluoride from phosphate is discussed taking into account existing technologies.

Calix[4]pyrrole derivative: recognition of fluoride and mercury ions and extracting properties of the receptor-based new material.

A calix[4]pyrrole derivative, namely, meso-tetramethyl tetrakis (4-phenoxy methyl ketone) calix[4]pyrrole, 1, was synthesized and structurally (1H NMR) and thermodynamically characterized. The complexing properties of this receptor with a wide variety of anions and cations in dipolar aprotic media (acetonitrile, propylene carbonate, and dimethyl sulfoxide) were investigated through 1H NMR and conductance studies. The former technique was used to assess whether or not complexation occurs and if so to identify the active sites of interaction of 1 with ions. The composition of the complexes was established by conductance measurements. It was found that in dipolar aprotic solvents, 1 interacts only with two polluting ions (fluoride and mercury). The complexation thermodynamics of 1 and these ions in these solvents is reported. The medium effect on the binding process involving the fluoride ion is discussed taking into account the solvation properties of reactants and the product. Complexes of moderate stability are found. Given that this is an important factor to consider for the recycling of the loaded material in extraction processes, 1 was treated with formaldehyde in basic medium leading to the production of a calix[4]pyrrole based material able to extract fluoride and mercury (II) ions from water. Thus the optimum conditions for the extraction of these ions from aqueous solutions were established. The material is easily recyclable using an organic acid. Final conclusions are given.

Sulfur-containing hetero-calix[4]pyrroles as mercury(II) cation-selective receptors: thermodynamic aspects.

Two sulfur-containing hybrid calix[4]pyrrole derivatives (III and IV) have been synthesized and fully characterized. Several analytical techniques (1H NMR, conductance measurements, UV-vis spectrophotometry, titration potentiometry, and titration calorimetry) have been used to assess the interaction between these hybrid calixpyrrole receptors and metal cations in acetonitrile and dimethylsulfoxide. The partition constants of calix[4]pyrrole, I, II, and IV in the acetonitrile-hexane solvent system and the solubilities of the ligands in various solvents at 298.15 K were determined. 1H NMR measurements reveal the sites of interaction of calixpyrrole ligands with metal cations in CD3CN. Conductance and UV-vis spectrophotometric measurements were performed to establish the composition of mercury(II) calixpyrrole complexes in acetonitrile at 298.15 K. Titration calorimetry was used to quantitatively assess Hg(II)-calixpyrrole interactions. Thus the thermodynamics of complexation of calixpyrrole ligands with the mercury(II) cation in acetonitrile at 298.15 K are reported. Potentiometric titrations were also used to establish the stepwise stability constants for the complexation of calix[3]thieno[1]pyrrole with the Hg(II) cation in acetonitrile at 298.15 K. The results show that replacement of one or more pyrrole units by thiophene rings in calix[4]pyrrole has tuned significantly the discrimination ability of these ligands between anions and enables the produced hybrid calixpyrroles to bind selectively with Hg(II) in acetonitrile. No interaction was observed between these ligands and other metal cations in acetonitrile.

Thermodynamics of ethyl p-tert-butylcalix[5]arene pentanoate and its cation complexes in nonaqueous media.

The solution behavior of ethyl p-tert-butylcalix[5]arene pentanoate, EtCalix(5), in various protic and aprotic solvents has been assessed from the standard Gibbs energies of transfer of this ligand from acetonitrile to other solvents. These data were derived from solubility measurements of EtCalix(5) in different media. It is concluded that in solvents in which metal cation salts are predominant as ionic species in solution (within a low concentration range), the solvation of the ligand will not contribute significantly to the thermodynamics of cation complexation as a result of the medium effect. Various analytical techniques were used to identify the sites of ligand-cation interaction (1H NMR) and the composition (conductance and calorimetric measurements) of the metal-ion complexes in the various solvents. Titration calorimetry (direct and competitive) was used to thermodynamically characterize the cation binding ability of EtCalix(5) and gain quantitative information on the complex stability and the factors controlling it. Given the large bulk of data reported in the literature wrongly placed under the thermodynamic umbrella, particular emphasis is made about the need of identifying the process taking place in solution prior to proceeding with its thermodynamic characterization. The results are compared with those for the ethyl ester derivative of the cyclic tetramer, EtCalix(4). It is concluded that in moving from EtCalix(4) to EtCalix(5), (i) the selectivity of the latter for cations is swallowed toward the larger cations and (ii) although the number of binding sites increases, these are not able to exert the efficient control upon the ligand-cation binding ability as that found for the tetramer ester and these cations in these solvents.

Modified calix[4]pyrrole receptor: solution thermodynamics of anion complexation and a preliminary account on the phosphate extraction ability of its oligomer.

A modified calix[4]pyrrole, namely meso-tetramethyl-tetrakis-(4-hydroxyphenyl) calix[4]pyrrole, 1, has been synthesized and characterized. (1)H NMR investigations in various deuterated solvents seems to indicate that this receptor interacts with acetone-d(6). The solution thermodynamics of 1 in various solvents is reported. Complexation studies in CD(3)CN show that the NH and OH functionalities of 1 are the active sites of its interaction with the fluoride and the dihydrogen phosphate anions. The composition of the anion complexes was established through conductance measurements. In all cases, 1:1 complexes are formed. The thermodynamics of anion complexation in acetonitrile and N,N-dimethylformamide is discussed comparatively with previous reported data for the parent calix[4]pyrrole, 2, and these anions in these solvents. The medium effect on anion complexation is discussed in terms of the solvation properties of the reactants and the product in acetonitrile and N,N-dimethylformamide. An oligomeric material containing 1 as anchor group was synthesized and characterized by mass spectrometry. Preliminary studies have been performed to assess the extracting properties of this oligomer for the removal of phosphates from aqueous solutions. The effects of pH, temperature on the extraction of this anion salt from water, as well as the kinetics of the process (fast) were investigated.

Calix[4]pyrrole for the removal of arsenic (III) and arsenic (V) from water.

Although extensive research has been carried on anion complexation reactions involving calix[4]pyrrole, nothing has been reported regarding this receptor and its interaction with arsenic species. The fact that a single step reaction is required for the synthesis of this receptor, calls upon the need to explore its removal ability for these species from water as a starting point for the development of a new technological approach for water remediation purposes based on Supramolecular Chemistry. This paper reports a detailed study on the interactions involving calix[4]pyrrole with As(III) and As(V). The interaction of As species and calix[4]pyrrole was assessed by 1H NMR using a phase transfer approach aided by molecular simulation studies. The X-ray spectrum confirms the presence of arsenic species in the solid receptor. Optimal conditions for removing As(III) and As(V) from water were established. The kinetics of extraction is fast and calix[4]pyrrole is able to remove 15.28 and 14.29mg/g of arsenate and arsenite respectively. Material was tested for removing arsenic species from real samples collected from different contaminated sites in Argentina. Percentages of arsenate, arsenite and organic arsenic removed from these samples are higher than 85%.

A preliminary observation of additive thermodynamic contribution of pendant arms to the complexation of calixarene derivatives with mercury(II).

An additive thermodynamic contribution of pendant arms to the complexation of calixarene derivatives with mercury(II) in acetonitrile is for the first time demonstrated.

Calixarene and resorcarene based receptors: from structural and thermodynamic studies to the synthesis of a new mercury(II) selective material.

Materials used in current technological approaches for the removal of mercury lack selectivity. Given that this is one of the main features of supramolecular chemistry, receptors based on calix[4]arene and calix[4]resorcarene containing functional groups able to interact selectively with polluting ions while discriminating against biologically essential ones were designed. Thus two receptors, a partially functionalized calix[4]arene derivative, namely, 5,11,17,23-tetra-tert-butyl [25-27-bis(diethyl thiophosphate amino)dihydroxy] calix[4]arene (1) and a fully functionalized calix[4]resorcarene, 4,6,10,12,16,18,22,24-diethyl thiophosphate calix[4]resorcarene (2) are introduced. Mercury(II) was the identified target due to the environmental and health problems associated with its presence in water Thus following the synthesis and characterization of 1 and 2 in solution ((1)HNMR) and in the solid state (X-ray crystallography) the sequence of experimental events leading to cation complexation studies in acetonitrile and methanol ((1)H NMR, conductance, potentiometric, and calorimetric measurements) with the aim of assessing their behavior as mercury selective receptors are described. The cation selectivity pattern observed in acetonitrile follows the sequence Hg(II) > Cu(II) > Ag(I). In methanol 1 is also selective for Hg(II) relative to Ag(I) but no interaction takes place between this receptor and Cu(II) in this solvent. Based on previous results and experimental facts shown in this paper, it is concluded that the complexation observed with Cu(II) in acetonitrile occurs through the acetonitrile-receptor adduct rather than through the free ligand. Receptor 2 has an enhanced capacity for uptaking Hg(II) but forms metalate complexes with Cu(II). These studies in solution guided the inmobilization of receptor 1 into a silica support to produce a new and recyclable material for the removal of Hg(II) from water. An assessment on its capacity to extract this cation from water relative to Cu(II) and Ag (I) shows that the cation selectivity pattern of the inmobilized receptor is the same as that observed for the free receptor in methanol. These findings demonstrate that fundamental studies play a critical role in the selection of the receptor to be attached to silicates as well as in the reaction medium used for the synthesis of the new decontaminating agent.

Selective interaction of lower rim calix[4]arene derivatives and bivalent cations in solution. Crystallographic evidence of the versatile behavior of acetonitrile in lead(II) and cadmium(II) complexes.

The interaction of lower rim calix(4)arene derivatives containing ester (1) and ketone (2) functional groups and bivalent (alkaline-earth, transition- and heavy-metal) cations has been investigated in various solvents (methanol, N,N-dimethylformamide, acetonitrile, and benzonitrile). Thus, 1H NMR studies in CD3OD, C3D7NO, and CD3CN show that the interaction of these ligands with bivalent cations (Mg2+, Ca2+, Sr2+, Ba2+, Hg2+, Pb2+, Cd2+) is only observed in CD3CN. These findings are corroborated by conductance measurements in these solvents including benzonitrile, where changes upon the addition of the appropriate ligand (1 or 2) to the metal-ion salt only occur in acetonitrile. Thus, in this solvent, plots of molar conductance against the ligand/metal cation ratio reveal the formation of 1:1 complexes between these ligands and bivalent cations. Four metal-ion complex salts resulting from the interaction of 1 and 2 with cadmium and lead, respectively, were isolated and characterized by X-ray crystallography. All four structures show an acetonitrile molecule sitting in the hydrophobic cavity of the ligand. The mode of interaction of the neutral guest in the cadmium(II) complexes differs from each other and from that found in the lead(II) complexes and provides evidence of the versatile behavior of acetonitrile in binding processes involving calix(4)arene derivatives. The thermodynamics of complexation of these ligands and bivalent cations in acetonitrile is reported. Thus, the selective behavior of 1 and 2 for bivalent cations is for the first time demonstrated. The role of acetonitrile in the complexation process in solution is discussed on the basis of 1H NMR and X-ray crystallographic studies. It is suggested that the complexation of 1 and 2 with bivalent cations is likely to involve the ligand-solvent adducts rather than the free ligand. Plots of complexation Gibbs energies against the corresponding data for cation hydration show a selectivity peak which is explained in terms of the predominant role played by cation desolvation and ligand binding energy in complex formation involving metal cations and macrocycles in solution. A similar peak is found in terms of enthalpy suggesting that for most cations (except Mg2+) the selectivity is enthalpically controlled. The ligand effect on the complexation process is quantitatively assessed. Final conclusions are given highlighting the role of the solvent in complexation processes involving calix(4)arene derivatives and metal cations.