[Spatial Variation Characteristics, Influencing Factors, and Sources of Hydrogeochemical of Surface Water and Groundwater in Mountainous Area of Hutuo River].

Surface runoff has dropped sharply in the mountainous area of the Hutuo River, posing a huge challenge to the sustainable use of groundwater in the North China Plain (NCP). The Taihang Mountain area is the main recharge source area of groundwater in the NCP. An in-depth study of spatial variation characteristics, influencing factors, and sources of hydrogeochemical characteristics of surface water and groundwater in the mountainous area of the Hutuo River can facilitate a comprehensive understanding of regional water resource status and sustainable utilization of water resources. Based on isotopic, hydrogeochemical, and mathematical statistics methods, this study analyzed spatial variation of hydrochemical characteristics in surface water and groundwater and its sources and main controlling factors. The results showed that the river water, well water, and spring water were all recharged by atmospheric precipitation in the mountainous areas of the Hutuo River. Under the combined influence of natural factors and human factors, the hydrogeochemical characteristics of river, well, and spring water showed large spatial differences. On the whole, the hydrochemical types of mainstreams were relatively concentrated. In the upper and lower mining reach areas, the mainstream water chemical type was dominated by Ca·Mg-SO4·HCO3, whereas that in the natural vegetation area (middle reach:between Qingshui River and Longhua River) was dominated by Ca·Mg-HCO3·SO4. In the upper stream, the main hydrochemical type of the Yukou River and Ehe River tributaries was Ca·Mg-SO4·HCO3, which was consistent with that of the main stream. The main hydrochemical types of the Muma River and Qingshui River tributaries were Ca-HCO3, Ca·Mg-HCO3, and Ca·Mg-HCO3·SO4 in the midstream. The main hydrochemical types of the Mianhe River and Yehe River tributaries were Ca-SO4, Ca·Mg-SO4, and Ca·Mg-SO4·HCO3. Mineral dissolution was still the main controlling factor for the hydrochemical characteristics of surface water and groundwater in the mountainous area of the Hutuo River. The contribution rates were 69.86% and 18.84% for mineral dissolution and human activities, respectively. Therefore, in the future, water resource utilization in the upper reaches of the Hutuo River should not only consider the issue of water quantity but also a series of water environment problems such as nitrate pollution and mining pollution caused by human activities.

[Hydrochemical Characteristics and Factors of Surface Water and Groundwater in the Upper Yongding River Basin].

The Yongding River basin is an important water conservation and ecological barrier area in the Northwest of Hebei Province. Reduced runoff and deterioration of the water environment in this area have become increasingly prominent under the effects of climate change and intensive human activities. Clarifying the chemical characteristics and factors of surface water and groundwater in the upper Yongding River basin can provide data and support for the sustainable use of water resources. Stable isotopes of hydrogen and oxygen (δ2H and δ18O) were used to study the sources of surface water and groundwater. Mathematical statistics and hydrogeochemical methods were then used to analyze the regional hydrogeochemical processes and factors of surface water and groundwater. The results showed that precipitation was the main source of surface water and groundwater. Under the effects of natural factors and human activities, the Yang River and Sanggan River basins exhibited significant differences in surface water chemistry. The sub-basins were ranked by ion concentration as follows: Sanggan River>Yang River. The main cation and anions of the Sanggan River basin were Na+, Cl-, and SO42-, while in the Yang River basin, Ca2+ and HCO3- were the most common. The water chemistry of the Sanggan River exhibited greater variation than that of the Yang River. Surface water chemistry were mainly controlled by mineral dissolution and evaporation, but human activities were reflected in different sub-basins. Surface water in the Sanggan River basin was affected by industrial wastewater discharge, while that of the Yang River basin was affected by agricultural production and cities. However, the continuous increase of Cl- and SO42- concentrations, caused by industrial wastewater discharge and acid rain, was the limiting factor for sustainable use of surface water resources. In future, surface water in Sanggan River basin should be used with consideration to the effects of both total salinity and chemical composition of the water, while in Yang River, a focus should be placed on total salinity. The use of surface water resources in accordance with local conditions is an effective measure for the sustainable use of water resources and the restoration of groundwater levels in this region.

Synthesis and iron chelating properties of hydroxypyridinone and hydroxypyranone hexadentate ligands.

Chelation therapy has become an important therapeutic approach for some diseases. In attempt to identify clinically useful chelators, four hexadentate ligands were synthesized by conjugating the corresponding bidentate ligands (3-hydroxypyridin-4-one (3,4-HOPO), 3-hydroxypyridin-2-one (3,2-HOPO), 1-hydroxypyridin-2-one (1,2-HOPO), and 3-hydroxypyran-4-one) each with a free amino group to a tripodal acid. Their pKa values and affinities for iron(iii) were investigated. The pFe3+ values of the hexadentate pyridinones 1 (3,4-HOPO), 3 (3,2-HOPO) and 4 (1,2-HOPO), and the pyranone 2 was found to follow the sequence 1 > 4 ≫ 3 > 2, which is different to the pFe3+ value sequence of the corresponding bidentate forms (3,4-HOPO ≫ 3,2-HOPO > 1,2-HOPO > 3-hydroxypyranone). Hexadentate 3,4-HOPOs and 1,2-HOPOs have the greatest potential as iron scavenging agents.

[Source of Nitrate in Surface Water and Shallow Groundwater Around Baiyangdian Lake Area Based on Hydrochemical and Stable Isotopes].

In order to study the source of nitrate in surface water and groundwater near a domestic sewage discharge river in the Baiyangdian watershed, including the Fuhe River and Baiyangdian Lake, shallow groundwater and deep groundwater samples were collected in July 2014.Water chemistry and stable isotopes (δ2 H and δ18O) were used to study the relationship between the surface water and groundwater. δ15 N was used to explore the source of nitrate. The results show that urban and rural domestic sewage discharge to Fuhe River and then experience evaporation. Shallow groundwater is affected by the Fuhe River, Baiyangdian Lake, and lateral recharge from groundwater in the Taihang Mountain area. There are 16.7% of shallow groundwater samples exceeds the NO3- threshold for drinking water according to the World Health Organization standard. Due to the effect of self-purification capacity, the NO3- mass concentration in the Fuhe River is higher in the upstream area than in the downstream area. Due the regional water flow from northwest to southeast, the NO3- mass concentration in the shallow groundwater is higher in the south bank area than in north bank area. The shallow groundwater near the Fuhe River and Baiyangdian Lake is recharged by surface water. In addition, soil, fertilizer, and point sources are also major sources for groundwater nitrate. Urban and rural residential living and agricultural production activities are the main reasons for surface water and groundwater nitrate.

Systematic comparison of the mono-, dimethyl- and trimethyl 3-hydroxy-4(1H)-pyridones - Attempted optimization of the orally active iron chelator, deferiprone.

A range of close analogues of deferiprone have been synthesised. The group includes mono-, di- and tri-methyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe(3+) values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NH-containing hydroxy-4(1H)-pyridones were found to be marginally more lipophilic than the corresponding N-Me containing analogues. This same group are also metabolised less efficiently by Phase 1 hydroxylating enzymes than the corresponding N-Me analogues. As result of this study, three compounds have been identified for further investigation centred on neutropenia and agranulocytosis.

Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains.

A range of hexadentate 3-hydroxypyridin-4-ones have been synthesized. These compounds were found to possess a high affinity for iron(III), with logK1 values of about 34 and pFe values over 30. Antimicrobial assays indicated that they can inhibit the growth of three clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) and three clinical isolates of Pseudomonas, suggesting that hexadentate 3-hydroxypyridin-4-ones have potential application in the treatment of wound infections.

[Distribution Characteristics and Source of Fluoride in Groundwater in Lower Plain Area of North China Plain: A Case Study in Nanpi County].

There is an obvious regional contradiction between water resources and agricultural produce in lower plain area of North China, however, excessive fluorine in deep groundwater further limits the use of regional water resources. In order to understand the spatial distribution characteristics and source of F(-) in groundwater, study was carried out in Nanpi County by field survey and sampling, hydrogeochemical analysis and stable isotopes methods. The results showed that the center of low fluoride concentrations of shallow groundwater was located around reservoir of Dalang Lake, and centers of high fluoride concentrations were located in southeast and southwest of the study area. The region with high fluoride concentration was consistent with the over-exploitation region of deep groundwater. Point source pollution of subsurface drainage and non-point source of irrigation with deep groundwater in some regions were the main causes for the increasing F(-) concentrations of shallow groundwater in parts of the sampling sites. Rock deposition and hydrogeology conditions were the main causes for the high F(-) concentrations (1.00 mg x L(-1), threshold of drinking water quality standard in China) in deep groundwater. F(-) released from clay minerals into the water increased the F(-) concentrations in deep groundwater because of over-exploitation. With the increasing exploitation and utilization of brackish shallow groundwater and the compressing and restricting of deep groundwater exploitation, the water environment in the middle and east lower plain area of North China will undergo significant change, and it is important to identify the distribution and source of F(-) in surface water and groundwater for reasonable development and use of water resources in future.

Design, synthesis, and antimicrobial evaluation of hexadentate hydroxypyridinones with high iron(III) affinity.

A range of hexadentate 3-hydroxypyridin-4-ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO-iron complexes (logK1 ) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram-positive and Gram-negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 µg/mL, respectively. These results indicate that hexadentate 3-hydroxypyridin-4-ones have potential application as antimicrobial agents, especially in the treatment of wound infection.

Design and synthesis of hydroxypyridinone-L-phenylalanine conjugates as potential tyrosinase inhibitors.

A range of hydroxypyridinone-L-phenylalanine conjugates were synthesized starting from kojic acid. Their tyrosinase activity was determined, and it was found that one of the compounds ((S)-(5-(benzyloxy)-1-octyl-4-oxo-1,4-dihydropyridin-2-yl)methyl 2-amino-3-phenylpropanoate, 5e) showed potent inhibitory effect against mushroom tyrosinase, the IC50 values for monophenolase and diphenolase activities being 12.6 and 4.0 µM, respectively. It was also demonstrated that these conjugates are mixed-type inhibitors, suggesting they could bind to both the free enzyme and the enzyme-substrate complexes. MTT assay indicated that 5e was nontoxic to three cell lines. This compound may find applications in food preservation and cosmetics.

Synthesis and in-vitro antimicrobial evaluation of a high-affinity iron chelator in combination with chloramphenicol.

OBJECTIVES: The objectives of this study were first to design and synthesize a hexadentate chelator with high iron(III) affinity and, second, to evaluate its antimicrobial activity in the presence and absence of chloramphenicol. METHODS: A hexadentate ligand was synthesized by conjugating a protected bidentate compound onto a tripodal structure. The pKa values and iron affinity of the chelator were determined by spectophotometric titration. Minimum inhibitory concentrations were determined by visual inspection of broth turbidity. The bactericidal rates were calculated by counting the colony numbers on a light board after incubation with and without an antimicrobial agent. KEY FINDINGS: A hexadentate 3-hydroxypyridin-4-one was found to possess a high affinity for iron(III), with a pFe value of 31.2 (negative logarithm of concentration of the free iron(III) in solution (when [Fe³âº](Total) = 10⁻6) M; [Ligand](Total) = 105 M; pH = 7.4). We found that this chelator had an appreciable inhibitory effect in vitro against the two bacterial strains Providencia stuartii and Staphylococcus aureus, particularly in the presence of chloramphenicol. CONCLUSIONS: A 3-hydroxypyridin-4-one hexadentate ligand has potential as an antimicrobial agent. Combination therapy with this iron chelator plus chloramphenicol has potential for the treatment of extracellular infections.

Prediction of 3-hydroxypyridin-4-one (HPO) log K1 values for Fe(III).

As a means to aid in the design of 3-hydroxypyridin-4-ones (HPOs) intended for use as therapeutic Fe(3+) chelating agents, a novel methodology has been developed using quantum mechanical (QM) calculations for predicting the iron binding affinities of the compounds (more specifically, their log K(1) values). The reported/measured HPO log K(1) values were verified through their correlation with the corresponding sum of the compounds' ligating group pK(a) values. Using a training set of eleven HPOs with known log K(1) values, reliable predictions are shown to be obtained with QM calculations using the B3LYP/6-31+G(d)/CPCM model chemistry (with Bondi radii, and water as solvent). With this methodology, the observed log K(1) values for the training set compounds are closely matched by the predicted values, with the correlation between the observed and predicted values giving r(2) = 0.9. Predictions subsequently made by this method for a test set of 42 HPOs of known log K(1) values gave predicted values accurate to within ±0.32 log units. In order to further investigate the predictive power of the method, four novel HPOs were synthesised and their log K(1) values were determined experimentally. Comparison of these predicted log K(1) values against the measured values gave absolute deviations of 0.22 (13.87 vs. 14.09), 0.02 (14.31 vs. 14.29), 0.12 (14.62 vs. 14.50), and 0.13 (15.04 vs. 15.17). The prediction methodology reported here is the first to be provided for predicting the absolute log K(1) values of iron-chelating agents in the absence of pK(a) values.

Prediction of 3-hydroxypyridin-4-one (HPO) hydroxyl pKa values.

As an aid in optimising the design of 3-hydroxypyridin-4-ones (HPOs) intended for use as therapeutic Fe(3+) chelating agents, various quantum mechanical (QM) and semi-empirical (QSAR) methods have been explored for predicting the pK(a) values of the hydroxyl groups in these compounds. Using a training set of 15 HPOs with known hydroxyl pK(a) values, reliable predictions are shown to be obtained with QM calculations using the B3LYP/6-31+G(d)/CPCM model chemistry (with Pauling radii, and water as solvent). With this methodology, the observed hydroxyl pK(a) values for the training set compound are closely matched by the predicted pK(a) values, with the correlation between the observed and predicted values giving r(2) = 0.98. Predictions subsequently made by this method for a test set of 48 HPOs of known hydroxyl pK(a) values (11 of which were determined experimentally in this study), gave predicted pK(a) values accurate to within ±0.2 log units. In order to further investigate the predictive power of the method, two novel HPOs were synthesised and their hydroxyl pK(a) values were determined experimentally. Comparison of these predicted pK(a) values against the measured values gave absolute deviations of 0.13 (10.18 vs. 10.31) and 0.43 (5.58 vs. 5.15).

Synthesis, iron(III)-binding affinity and in vitro evaluation of 3-hydroxypyridin-4-one hexadentate ligands as potential antimicrobial agents.

Iron is a critical element for the survival of bacteria. We have designed and synthesized two novel 3-hydroxypyridin-4-one hexadentate ligands with high affinity for iron(III), which disrupt bacterial iron absorption. Biological studies demonstrate that these two chelators have significant inhibitory effect against both Gram-positive and Gram-negative bacteria, and therefore have potential as antimicrobial agents.

Synthesis and iron(III)-chelating properties of novel 3-hydroxypyridin-4-one hexadentate ligand-containing copolymers.

Iron overload is a critical clinical problem that can be prevented by the use of iron-specific chelating agents. An alternative method of relieving iron overload is to reduce the efficiency of iron absorption from the intestine by administering iron chelators, which can bind iron irreversibly to form nontoxic, kinetically inert complexes that are not absorbed and are therefore excreted in the feces. A series of polymeric chelators with various iron binding capacities were therefore prepared as nonabsorbable iron-selective additives. A novel 3-hydroxypyridin-4-one hexadentate ligand CP254 has been synthesized and incorporated into polymers by copolymerisation with N, N-dimethylacrylamide (DMAA), and N, N'-ethylene-bis-acrylamide (EBAA) using (NH4)2S2O8 as the initiator. The physicochemical properties of CP254 were determined, namely, log K = 33.2 and pFe(3+) = 27.24. The chelating capacity of the CP254-DMAA copolymers was determined at physiological pH. The iron(III) chelation was found to achieve 80% capacity after 1 h and was virtually complete after 5 h, which is much quicker than that of the commercially available chelating resin Chelex100. The chelating copolymers were found to be readily regenerated and reusable. The copolymers possess a high selectivity for iron(III). The conditional affinity (log K') for iron(III) at pH 7.46 was determined to be 26.55, which is not significantly different to that of the hexadentate ligand CP254 (log K' = 26.47). In vitro perfusion studies indicate that the polymeric chelators described in this study can reduce iron absorption from the intestine.

Iron binding dendrimers: a novel approach for the treatment of haemochromatosis.

A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.

High affinity iron(III) scavenging by a novel hexadentate 3-hydroxypyridin-4-one-based dendrimer: synthesis and characterization.

The synthesis of a novel iron(III)-selective hydroxypyridinone hexadentate-terminated dendritic chelator based on a benzene tricarbonyl core polyamine dendrimer is described. The iron-chelating ability of the dendritic chelator was demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and UV-vis spectroscopy. The physicochemical properties of the isolated hexadentate unit were also investigated. The dendrimer was found to possess an extremely high affinity for iron(III), namely logK=34.8, pFe3+=30.6.