Construction and demolition waste as a high-efficiency advanced process for organic pollutant degradation in Fenton-like reaction to approach circular economy.

The Fenton-like reaction is a promising organic wastewater treatment reaction among advanced oxidation processes (AOP), which has emerged to replace the conventional Fenton reaction. Recycled construction and demolition waste (CDW), which is porous and rich in iron, manganese, and magnesium, can be reused as a Fenton-like catalyst. This study proposes an AOP wastewater treatment strategy using recycled porous CDW mixed with hydrogen peroxide (H2O2) to decompose methylene blue (MB) wastewater. According to the apparent first-order rate (Kapp) of 10 ppm MB adsorption, CDW-3, having the highest specific surface area, also has the highest Kapp of 0.23 min-1 g-1. The optimized conditions recommended by the Taguchi method include a 0.3 g mL-1 CDW-3 concentration, a 0.254 g mL-1 H2O2 concentration, and 10 ppm MB, resulting in an about 2.01 min-1Kapp value. In addition, MB concentration is observed as the most influential factor for Kapp, which decreases with increasing MB concentration and is about 0.62 min-1 at 1000 ppm MB. Repeating the Fenton-like reaction five times at 100 p.m. MB using the same CDW-3, the Kapp is about 0.64 min-1, which is 86% of the initial run. The synergistic effect index (ξ) is defined to quantify the level of interaction between CDW and H2O2, which produces free radicals during the Fenton-like process. The ξ of CDW-3 is about 2.16. Overall, it is demonstrated that CDW is a promising catalyst for Fenton-like reactions, and the synergistic effect index (ξ) can be used as a reference index to evaluate the catalytic generation of free radicals between the catalyst and H2O2.

SAR of carbon-linked, 2-substituted purines: synthesis and characterization of AP23451 as a novel bone-targeted inhibitor of Src tyrosine kinase with in vivo anti-resorptive activity.

Targeted disruption of the pp60(src) (Src) gene has implicated this tyrosine kinase in osteoclast-mediated bone resorption and as a therapeutic target for the treatment of osteoporosis and other bone-related diseases. Here, we describe structure activity relationships of a novel series of carbon-linked, 2-substituted purines that led to the identification of AP23451 as a potent inhibitor of Src tyrosine kinase with antiresorptive activity in vivo. AP23451 features the use of an arylphosphinylmethylphosphinic acid moiety which confers bone-targeting properties to the molecule, thereby increasing local concentrations of the inhibitor to actively resorbing osteoclasts at the bone interface. AP23451 exhibited an IC50 = 68 nm against Src kinase; an X-ray crystal structure of the molecule complexed with Src detailed the molecular interactions responsible for its Src inhibition. In vivo, AP23451 demonstrated a dose-dependent decrease in PTH-induced hypercalcemia. Moreover, AP23517, a structurally and biochemically similar molecule with comparable activity (IC50 = 73 nm) except devoid of the bone-targeting element, demonstrated significantly reduced in vivo efficacy, suggesting that Src activity was necessary but not sufficient for in vivo activity in this series of compounds.

Bone-targeted Src kinase inhibitors: novel pyrrolo- and pyrazolopyrimidine analogues.

Src tyrosine kinase is a therapeutic target for bone diseases that has been validated by gene knockout studies. Furthermore, in vitro cellular studies implicate that Src has a positive regulatory role in osteoclasts and a negative regulatory role in osteoblasts. The potential use of Src inhibitors for osteoporosis therapy has been previously shown by novel bone-targeted ligands of the Src SH2 (e.g., AP22408) and non-bone-targeted, ATP-based inhibitors of Src kinase. Significant to this study, compounds 2-12 exemplify novel analogues of known pyrrolopyrimidine and pyrazolopyrimidine template-based Src kinase inhibitors that incorporate bone-targeting group modifications designed to provide tissue (bone) selectivity and diminished side effects. Accordingly, we report here the structure-based design, synthetic chemistry and biological testing of these compounds and proof-of-concept studies thereof.

Bone-targeted 2,6,9-trisubstituted purines: novel inhibitors of Src tyrosine kinase for the treatment of bone diseases.

Novel bone-targeted 2,6,9-trisubstituted purine template-based inhibitors of Src tyrosine kinase are described. Drug design studies of known purine compounds revealed that both positions-2 and -6 were suitable for incorporating bone-seeking moieties. A variety of bone-targeting groups with different affinity to hydroxyapatite were utilized in the study. Compound 3d was determined to be a potent Src inhibitor and was quite selective against a panel of other protein kinases.

Bone-targeted pyrido[2,3-d]pyrimidin-7-ones: potent inhibitors of Src tyrosine kinase as novel antiresorptive agents.

The design of bone-targeted pyrido[2,3-d]pyrimidin-7-ones as Src tyrosine kinase inhibitors is described. Leveraging SAR from known compounds and using structure-based methods, we were able to rapidly incorporate bone binding components, which maintained, and even increased potency against the target enzyme. Compound 4 displayed a high affinity for hydroxyapatite, a major constituent of bone, and demonstrated antiresoprtive activity in our cell-based assay.