Ewa Chmielewska

Measurements of temperature and strain sensitivities of a two-mode Bragg grating imprinted in a bow-tie fibre

A method for measuring the sensitivity of Bragg gratings to external parameters for different spatial and polarization modes is presented together with the results of measurements of sensitivity to temperature and elongation for LPx01, LPy01, LPx11 and LPy11 modes. The difference in response according to the type of mode shows the possibility of performing simultaneous temperature and elongation measurements using two-mode Bragg gratings.

Physiologic Activity of Bisphosphonates – Recent Advances

Received: September 14, 2015 Revised: April 12, 2016 Accepted: April 25, 2016 Abstract: Background: Bisphosphonates are drugs commonly used for the medication and prevention of diseases caused by decreased mineral density. Despite such important medicinal use, they display a variety of physiologic activities, which make them promising anti-cancer, antiprotozoal, antibacterial and antiviral agents.

Synthetic Procedures Leading towards Aminobisphosphonates

Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used reactions, as well as development of new procedures, are presented in this review, concentrating on recent achievements. Additionally, selected examples of aminobisphosphonate derivatization illustrate their usefulness for obtaining new diagnostic and therapeutic agents.

N-Arylaminomethylenebisphosphonates Bearing Fluorine Atoms: Synthesis and Antiosteoporotic Activity

GRAPHICAL ABSTRACT Abstract A series of N-phenyl and N-pyridyl-aminomethylenebisphosphonates substituted in their aromatic rings with fluorine atoms or trifluoromethyl groups have been synthesized by a three component approach. They were screened for potential antiosteoporetic activity using mouse macrophage-like J774E cells. Most of the compounds appeared to be moderate inhibitors of macrophage cells proliferation compared to known the antiosteoporetic drug, Incandronate. Their potency was compared with their structural analogues, hydroxymethylene-bisphosphonate 2 and ethylidenebisphosphonates 3, which appeared to be equipotent. Although the aminomethylenebisphosphonates 1 show low stability in aqueous solutions, the most stable, i.e., N-(3-trifluoromethylphenyl)-aminomethylenebisphosphonic acid, was chosen for in vivo testing on sheep with induced osteoporosis. This compound had marginal influence on the bone structure recovery.

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

Summary A convenient approach has been developed to α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues by α-phosphonylation, α-phosphinylation or α-phosphinoylation of 1-(N-acylamino)alkylphosphonates, that, in turn, are easily accessible from N-acyl-α-amino acids. Effective electrophilic activation of the α-position of 1-(N-acetylamino)alkylphosphonates was achieved by electrochemical α-methoxylation of these compounds in methanol, mediated with NaCl, followed by displacement of the methoxy group with triphenylphosphonium tetrafluoroborate to give hitherto unknown 1-(N-acetylamino)-1-triphenylphosphoniumalkylphosphonate tetrafluoroborates. The latter compounds react smoothly with trialkyl phosphites, dialkyl phosphonites or alkyl phosphinites in the presence of Hünig’s base and methyltriphenylphosphonium iodide in a Michaelis–Arbuzov-like reaction to give the expected alkylidenebisphosphonates, 1-phosphinylalkylphosphonates or 1-phosphinoylalkylphosphonates, respectively, in good yields.

Aminobisphosphonates based on cyclohexane backbone as coordinating agents for metal ions. Thermodynamic, spectroscopic and biological studies

Single and double amino-bisphosphonates were synthesized and tested for coordination capabilities towards Ca2+, Mg2+, Cu2+ and Ni2+ metal ions by means of potentiometry, UV-vis spectroscopy, mass spectrometry (ESI-MS) and isothermal titration calorimetry (ITC), as well as for cytotoxic activity by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Half minimal inhibitory concentrations (IC50) were determined with respect to two cell lines (human melanoma A375 and human colorectal adenocarcinoma HT29). Basing the structure of compounds on a cyclohexane ring allowed for a slight reduction of high hydrophilic character of the studied bisphosphonates (BPs). The ligands efficiently bind the examined metal ions forming complex equilibria with diversified stoichiometry of equimolar, polynuclear species and biscomplexes. Both ligands as well as their Ca2+ and Mg2+ complexes show selective antiproliferative activity toward the studied cancer cell lines. Given the thermodynamic and biological data, it can be assumed that ligands are good candidates for linking compounds that may be used in the design of new drug delivery systems. In this approach, one bisphosphonate moiety acts as a bone-targeting molecule, while another molecule can be readily attached to the second donor function (primary amine or bisphosphonate).

New aspects of coordination chemistry and biological activity of NTMP-related diphosphonates containing a heterocyclic ring

Two analogues of nitrilotris(methylene-phosphonic acid) (NTMP), namely L1 = N-(methylene-2-pyridine)-N,N,-di-(methylenephosphonate) and L2 = N-(methylene-1H-benzimidazol)-N,N,-di-(methylenephosphonate) in which one of the phosphonic arms was replaced by a heterocyclic moiety, pyridine and benzimidazole, were studied in terms of coordination chemistry towards transition (Cu2+, Ni2+, Zn2+) and alkaline-earth metal ions (Ca2+ and Mg2+) by means of potentiometry, UV-vis spectroscopy, mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC). The cytotoxicity of the ligands as well as their Zn2+, Ca2+ and Mg2+ complexes was tested against various cell lines (human melanoma A375 and human colon adenocarcinoma HT29) revealing a selective antitumor effect in vivo. Both of the ligands exhibit a potent inhibitory effect on tumor cell migration and experimental metastasis. Potentiometric and ESI-MS measurements have shown the existence of monomeric species only, without the presence of biscomplexes or polynuclear species. The conditional stability constants (log Kc) of the Zn2+, Ca2+, and Mg2+ complexes were determined independently by two methods for both of the studied ligands and are a first example of comprehensive potentiometry/ITC studies made for phosphonic acid complexation. No significant differentiation in coordination models for the studied set of metal ions was noticed; however, as expected due to the different metal ion natures, the complexes revealed dissimilar thermodynamic stability and behavior, depending on the metal ion and pH used. The possible structures of the complexes formed are discussed on the basis of spectroscopic and spectrometric results.

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.

Improvement of large animal model for studying osteoporosis

Abstract The aim of the study was to determine the impact of steroidal medications on the structure and mechanical properties of supporting tissues of sheep under experimentally-induced osteoporosis. A total of 21 sheep were used, divided into three groups: a negative control (KN) (n = 3), a positive control (KP) (n = 3) with ovariectomy, and a steroidal group (KS) (n = 15) with ovariectomy and glucocorticosteroids. All animals were kept on a low protein and mineral diet and had limited physical activity and access to sunlight. Quantitative computed tomography was the examination method. The declines in the examined parameter values in the KS group were more than three times higher than in the KN group. The study suggests that a glucocorticosteroidal therapy accelerates and intensifies processes taking place in the course of osteoporosis. The combination of glucocorticosteroids with ovariectomy, a restrictive diet, limited physical activity, and no access to sunlight leads to a decrease in radiological bone density.

Characteristics of Bragg grating imprinted in highly birefringent side-hole fiber

We present characteristics of Bragg grating imprinted in highly birefringent side-hole fiber. Using specially developed methods we measured spectral sensitivity of the grating (dλB/dX) and the phase sensitivity (dΦ/dX) of the host side-hole fiber to temperature and hydrostatic pressure for each polarization mode. The measurement results for both, the grating and the host fiber, show high difference in responses to pressure and almost identical responses to temperature versus mode polarization. This feature of the Bragg grating imprinted in the side-hole fiber can be potentially used for simultaneous sensing of these two parameters by interrogating wavelength shifts for orthogonally polarized modes. We also present the results of modeling of the phase sensitivities to pressure and temprature for the host side-hole fiber and compare them with experimental values.