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Fosmidomycin (FOS) is a naturally occurring compound active against the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) enzyme in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, and using it as a template for lead structure design is an effective strategy to develop new active compounds. In this work, by replacing the hydroxamate unit of FOS with pyrazole, isoxazole and the related heterocycles that also have metal ion binding affinity, while retaining the monophosphonic acid in FOS or replacing it with a bisphosphonic acid group, heterocycle-containing mono- and bisphosphonic acid compounds as FOS analogs were designed. The key steps involved in the facile synthesis of these FOS analogs included the Michael addition of diethyl vinylphosphonate or tetraethyl vinylidenebisphosphonate to β-dicarbonyl compounds and the subsequent cyclic condensation with hydrazine or hydroxylamine. Two additional isoxazolinone-bearing FOS analogs were synthesized via the Michaelis–Becker reaction with diethyl phosphite as a key step. The bioactivity evaluation on model plants demonstrated that several compounds have better herbicidal activities compared to FOS, with the most active compound showing a 3.7-fold inhibitory activity on Arabidopsis thaliana, while on the roots and stalks of Brassica napus L. and Echinochloa crus-galli in a pre-emergence inhibitory activity test, the activities of this compound were found to be 3.2- and 14.3-fold and 5.4- and 9.4-fold, respectively, and in a post-emergency activity test on Amaranthus retroflexus and Echinochloa crus-galli, 2.2- and 2.0-fold inhibition activities were displayed. Despite the significant herbicidal activity, this compound exhibited a DXR inhibitory activity lower than that of FOS but comparable to that of other non-hydroxamate DXR inhibitors, and the dimethylallyl pyrophosphate rescue assay gave no statistical significance, suggesting that a different target might be involved in the inhibiting process. This work demonstrates that using bioisosteric replacement can be considered as a valuable strategy to discover new FOS analogs that may have high herbicidal activities. [ABSTRACT FROM AUTHOR]

This study evaluated the ability of bisphosphonates (BPAs) of different molecular structures to mitigate the calcification of porcine aortic wall (PAW) and bovine jugular vein wall (BJVW). Tissues cross‐linked with glutaraldehyde (GA) or diepoxide (DE) were modified with pamidronic acid (PAM), alendronic acid (ALE), neridronic acid (NER) (type 1 BPAs); 2‐(2′‐carboxyethylamino)ethylidene‐1,1‐bisphosphonic acid (CEABA), 2‐(5‐carboxypentylamino)ethylidene‐1,1‐bisphosphonic acid (CPABA) (type 2); and zoledronic acid (ZOL) (type 3). After implanting the tissue samples subcutaneously in 100 rats, calcification was examined using atomic absorption spectrophotometry (60‐day explants) and light microscopy after von Kossa staining (10‐ and 30‐day explants). The calcium contents in GA‐BJVW and GA‐ and DE‐PAW increased up to 100–120 mg/g after 60 days, while being 3 times lower in DE‐BJVW. In modified and nonmodified PAW samples, calcium phosphates appeared by day 10 and were associated with elastic fibers and devitalized cellular elements. In all groups of BJVW samples, mineralization began in elastic fibers near the subendothelial layer. In addition, calcified collagen was found in the GA‐BJVW samples. Minimal calcification was found in GA‐PAW treated with type 1 BPAs and CEABA. For DE‐PAW and GA‐BJVW, the calcium level significantly decreased with PAM and CEABA. Meanwhile, ALE and NER were effective for DE‐BJVW. [ABSTRACT FROM AUTHOR]

This study evaluated the ability of bisphosphonates (BPAs) of different molecular structures to mitigate the calcification of porcine aortic wall (PAW) and bovine jugular vein wall (BJVW). Tissues cross‐linked with glutaraldehyde (GA) or diepoxide (DE) were modified with pamidronic acid (PAM), alendronic acid (ALE), neridronic acid (NER) (type 1 BPAs); 2‐(2′‐carboxyethylamino)ethylidene‐1,1‐bisphosphonic acid (CEABA), 2‐(5‐carboxypentylamino)ethylidene‐1,1‐bisphosphonic acid (CPABA) (type 2); and zoledronic acid (ZOL) (type 3). After implanting the tissue samples subcutaneously in 100 rats, calcification was examined using atomic absorption spectrophotometry (60‐day explants) and light microscopy after von Kossa staining (10‐ and 30‐day explants). The calcium contents in GA‐BJVW and GA‐ and DE‐PAW increased up to 100–120 mg/g after 60 days, while being 3 times lower in DE‐BJVW. In modified and nonmodified PAW samples, calcium phosphates appeared by day 10 and were associated with elastic fibers and devitalized cellular elements. In all groups of BJVW samples, mineralization began in elastic fibers near the subendothelial layer. In addition, calcified collagen was found in the GA‐BJVW samples. Minimal calcification was found in GA‐PAW treated with type 1 BPAs and CEABA. For DE‐PAW and GA‐BJVW, the calcium level significantly decreased with PAM and CEABA. Meanwhile, ALE and NER were effective for DE‐BJVW. [ABSTRACT FROM AUTHOR]

A bisphosphonic acid type extraction reagent has been synthesised and employed to investigate the extraction behaviour towards rare-earth metals. The new reagent exhibited extremely high extraction ability for these ions. This ability was also accompanied by low leakage of extractant into the aqueous phase reflecting the reagent's hydrophobic nature and the presence of partially undissociated phosphonic acid groups. [ABSTRACT FROM AUTHOR]

Herein we describe our recent advances in the synthesis of new bisphosphonates, containing adenosines, adenine moiety as well as reactive aminoacetal fragment and calix[4]resorcinols framework. For the synthesis of these compounds we used three main approaches: Michael addition of nucleophilic amines (adenosines, adenines and aminoacetaldehyde) to (tetraethyl)ethenylidene-1,1-bisphosphonate and tetrakis(trimethylsilyl)ethenylidene-1,1-bisphosphonate); acid catalyzed condensation of bisphosphonic acid derivatives, containing acetal group with polyphenols; formation of onium salts of bisphosphonic acids with adenosine and aminomethylated calix[4]resorcinols. [ABSTRACT FROM AUTHOR]

The first monomers containing both phosphonate and bisphosphonate (M1) or phosphonic and bisphosphonic acid (M2) functionalities are synthesized, aiming to improve binding abilities of self‐etching adhesive systems and composites: An amine having both phosphonate and bisphosphonate functionalities is prepared via Michael addition reaction between diethyl (6‐aminohexyl)phosphonate and tetraethyl vinylidene bisphosphonate, its reaction with 2‐isocyanatoethyl methacrylate gives M1 which is converted to M2 by selective dealkylation of the phosphonate/bisphosphonate ester groups. Their copolymerization with commercial dental monomers (bisphenol A glycidyl methacrylate, triethylene glycol dimethacrylate, and 2‐hydroxyethyl methacrylate) investigated by photo‐differential scanning calorimetry shows adequate photopolymerization rate and conversion. X‐ray diffraction, Fourier transform infrared, and X‐ray photoelectron spectroscopy analyses of M2‐treated hydroxyapatite particles show formation of stable M2‐calcium salts. These monomers are assessed to be not toxic according to MTT standards by in vitro cytotoxicity studies with NIH 3T3, U2OS, and Saos‐2 cells. All these properties make these monomers potential candidates as biocompatible components for dental adhesives and composites. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2739–2751 To improve efficiencies of dental materials, novel monomers containing both phosphonate and bisphosphonate/phosphonic and bisphosphonic acid are synthesized. Interaction of monomers with hydroxyapatite (mineral structure of teeth) is analyzed; their copolymerization rate and yield with the dental monomers are evaluated by using photo‐differential scanning calorimetry. [ABSTRACT FROM AUTHOR]

The reaction of o-phthaloyl chloride with sodium diethylphosphite led to the formation of new 3,3-bis(diethylphosphono)-1-(3H)-isobenzofurane 1. The reaction of bis-phosphonate with alkylamine occurs with replacement of an ester oxygen by an imine group to afford the crystalline isoindolyl-bis-phosphonate-a representative of this new type of organophosphorus heterocycles. [ABSTRACT FROM AUTHOR]

Currently, significant attention is attracted to the problem of the development of the specific architecture and composition of the surface layer in order to control the biocompatibility of implants made of titanium and its alloys. The titanium surface properties can be tuned both by creating an inorganic sublayer with the desired morphology and by organic top coating contributing to bioactivity. In this work, we developed a composite biologically active coatings based on hybrid molecules obtained by chemical cross-linking of amino acid bisphosphonates with a linear tripeptide RGD, in combination with inorganic porous sublayer created on titanium by plasma electrolytic oxidation (PEO). After the addition of organic molecules, the PEO coated surface gets nobler, but corrosion currents increase. In vitro studies on proliferation and viability of fibroblasts, mesenchymal stem cells and osteoblast-like cells showed the significant dependence of the molecule bioactivity on the structure of bisphosphonate anchor and the linker. Several RGD-modified bisphosphonates of β-alanine, γ-aminobutyric and ε-aminocaproic acids with BMPS or SMCC linkers can be recommended as promising candidates for further in vivo research. [ABSTRACT FROM AUTHOR]

The first bisphosphonic acid‐functionalized benzophenone (BP) and thioxanthone (TX) photoinitiators (PIs), BPBP and TXBP, are synthesized as a new class of water‐soluble PIs for free radical polymerization. BPBP shows excellent solubility (28 g L−1) in water at ambient temperature, compared to TXBP (0.05 g L−1) and also the commercial PI Irgacure 2959 (5 g L−1). BPBP and TXBP show UV–vis absorption at ≈260 (ε = 12912) and 405 (ε = 3314) nm in water. Photopolymerization results demonstrate that they can successfully initiate the photopolymerization of poly(ethylene glycol) diacrylate (Mn = 250 D) in the presence of bis‐(4‐tert‐butylphenyl)‐iodonium hexafluorophosphate (Iod). The photochemical mechanisms are investigated by electron‐spin resonance‐spin trapping, fluorescence, and steady‐state photolysis techniques. [ABSTRACT FROM AUTHOR]