178489-05-9Relevant academic research and scientific papers
Nitric oxide reactivity accounts for N-nitroso-ciprofloxacin formation under nitrate-reducing conditions
Brienza, Monica,Chiron, Serge,Manasfi, Rayana,Sauvêtre, Andrés
, (2020)
The formation of N-nitroso-ciprofloxacin (CIP) was investigated both in wastewater treatment plants including nitrification/denitrification stages and in sludge slurry experiments under denitrifying conditions. The analysis of biological wastewater treatment plant effluents by Kendrick mass defect analysis and liquid chromatography - high resolution - mass spectrometry (LC[sbnd]HRMS) revealed the occurrence of N-nitroso-CIP and N-nitroso-hydrochlorothiazide at concentration levels of 34 ± 3 ng/L and 71 ± 6 ng/L, respectively. In laboratory experiments and dark conditions, produced N-nitroso-CIP concentrations reached a plateau during the course of biodegradation experiments. A mass balance was achieved after identification and quantification of several transformation products by LC[sbnd]HRMS. N-nitroso-CIP accounted for 14.3% of the initial CIP concentration (20 μg/L) and accumulated against time. The use of 4,5-diaminofluorescein diacetate and superoxide dismutase as scavengers for in situ production of nitric oxide and superoxide radical anion respectively, revealed that the mechanisms of formation of N-nitroso-CIP likely involved a nitrosation pathway through the formation of peroxynitrite and another one through codenitrification processes, even though the former one appeared to be prevalent. This work extended the possible sources of N-nitrosamines by including a formation pathway relying on nitric oxide reactivity with secondary amines under activated sludge treatment.
Ciprofloxacin conjugated to diphenyltin(iv): A novel formulation with enhanced antimicrobial activity
Bakas, T.,Banti, C. N.,Chrysouli, M. P.,Douvalis, A.,Hadjikakou, S. K.,Hatzidimitriou, A. G.,Kourkoumelis, N.,Moushi, E. E.,Papachristodoulou, C.,Tasiopoulos, A. J.
, p. 11522 - 11535 (2020)
The metalloantibiotic of formula Ph2Sn(CIP)2 (CIPTIN) (HCIP = ciprofloxacin) was synthesized by reacting ciprofloxacin hydrochloride (HCIP·HCl) (an antibiotic in clinical use) with diphenyltin dichloride (Ph2SnCl2DPTD). The complex was characterized in the solid state by melting point, FT-IR, X-ray Powder Diffraction (XRPD) analysis, 119Sn M?ssbauer spectroscopy, X-ray Fluorescence (XRF) spectroscopy, and Thermogravimetry/Differential Thermal Analysis (TG-DTA) and in solution by UV-Vis, 1H NMR spectroscopic techniques and Electrospray Ionisation Mass Spectrometry (ESI-MS). The crystal structure of CIPTIN and its processor HCIP was also determined by X-ray crystallography. The antibacterial activity of CIPTIN, HCIP·HCl, HCIP and DPTD was evaluated against the bacterial species Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZs). CIPTIN shows lower MIC values than those of HCIP·HCl (up to 4.2-fold), HCIP (up to 2.7-fold) or DPTD (>135-fold), towards the tested microbes. CIPTIN is classified into bactericidal agents according to MBC/MIC values. The developing IZs are 40.8 ± 1.5, 34.0 ± 0.8, 36.0 ± 1.1 and 42.7 ± 0.8 mm, respectively which classify the microbes P. aeruginosa, E. coli, S. aureus and S. epidermidis to susceptible ones to CIPTIN. These IZs are greater than the corresponding ones of HCIP·HCl by 1.1 to 1.5-fold against both the tested Gram negative and Gram positive bacteria. CIPTIN eradicates the biofilm of P. aeruginosa and S. aureus more efficiently than HCIP·HCl and HCIP. The in vitro toxicity and genotoxicity of CIPTIN were tested against human skin keratinocyte cells (HaCaT) (IC50 = 2.33 μM). CIPTIN exhibits 2 to 9-fold lower MIC values than its IC50 against HaCaT, while its genotoxic effect determined by micronucleus assay is equivalent to the corresponding ones of HCIP·HCl or HCIP.
Microwave assisted amination of quinolone carboxylic acids: An expeditious synthesis of fluoroquinolone antibacterials
Reddy,Baskaran
, p. 6775 - 6777 (2001)
A facile amination of quinolone carboxylic acids to fluoroquinolone antibacterials under microwave irradiation is described.
Use of tetrabenzo[a,c,g,i]fluorene as an anchor group for the solid/solution phase synthesis of ciprofloxacinρ
Hay, Alastair M.,Hobbs-Dewitt, Sheila,MacDonald, Alasdair A.,Ramage, Robert
, p. 8721 - 8724 (1998)
The affinity of tetrabenzo[a,c,g,i]fluorene for charcoal has been applied successfully to provide an alternative to existing solid phase synthesis methodology. In a synthesis of the quinolone antibacterial, Ciprofloxacin, traditional solution phase synthesis has been coupled with efficient pseudo-solid phase purification.
A solid phase approach to quinolones using the DIVERSOMER technology
MacDonald, Alasdair A.,DeWitt, Sheila H.,Hogan, Eleonora M.,Ramage, Robert
, p. 4815 - 4818 (1996)
The first example of a library of the quinolone antibacterial agents prepared by solid phase organic synthesis is described. Results of these studies and the parallel synthesis, isolation, purification and analysis of eight quinolones are discussed.
Enrofloxacin behavior in presence of soil extracted organic matter: An electrochemical approach
Antilén, Monica,Valencia, Camila,Peralta, Emilia,Canales, Camila,Espinosa-Bustos, Christian,Escudey, Mauricio
, p. 104 - 111 (2017)
In this work, a novel and simple method aimed at determining and quantifying Enrofloxacin in presence of Natural Organic Matter (NOM) is proposed. The method was based on the electrochemical oxidation of Enrofloxacin by using cyclic voltammetry as technique. It was found that this analyte presents a good electroactivity, in absence and in presence of NOM. However, this electrochemical behavior is highly pH-dependent, since the reaction is more favorable when less acid the media is. At this point, different pH values were studied in order to corroborate this phenomenon. Additionally, kinetic studies were done to determine the control of the reaction, the number of transferred electrons in the entire process and the rate determining step of the reaction by analyzing the Tafel slope. With these antecedents, a mechanism was proposed and the final product of the reaction was corroborated by using LC-MS. Finally, analytical parameters were studied with the aim of proposing this new method as an electrochemical sensor of Enrofloxacin. It was found that the method is highly linear, precise and accurate. Moreover, this method is not only sensitive but also selective to Enrofloxacin in presence of NOM, in comparison to spectrophotometric methods previously reported.
Crystal structure of C17H20FN3O 3 2+ ?cuBr4 2- ?h 2O
Vasiliev,Golovnev
, p. 809 - 812 (2011)
A new compound C17H20FN3O 3 2+ ?CuBr 4 2- ?H2O is synthesized in the crystal form, where C17H18FN 3O3 (CfH, ciprofloxacin) is 4-oxo-7-(1-piperazinyl)-6- fluoro-1-cyclopropyl-1,4-dihydroquinoline-3-carboxylic acid. Crystallographic data of ciprofloxacinium tetrabromocuprate(II) monohydrate, C17H 22Br4CuFN3O4: a = 8.214(1) A, b = 10.781(2) A, c = 13.703(2) A, α = 85.144(2)°, β = 79.119(2)°, γ = 84.018(2)°, V = 1182.5(4) A3, P 1 space group, Z = 2. Supramolecular architecture of the crystal differs from that established for C17H20FN3O 3 2+ ?CuCl 4 2- ?H2O by the absence of π-π interactions of the aromatic rings of CfH 3 2+ ions and also the structural motifs formed by intermolecular hydrogen bonds.
Unrecognized role of humic acid as a reductant in accelerating fluoroquinolones oxidation by aqueous permanganate
Zhou, Yang,Hu, Jianpeng,Gao, Yuan,Song, Yang,Pang, Su-Yan,Jiang, Jin
supporting information, p. 447 - 451 (2021/08/10)
A great concern has been raised regarding the issue of fluoroquinolones (FQs) in the environment. In this work, the transformation of FQs by commonly used oxidant permanganate (Mn(VII)) in the absence and presence of humic acid (HA), ubiquitously existing in aquatic environments, was systematically investigated. Here, the catalytic role of in-situ formed MnO2 on Mn(VII) oxidation of FQs depending on solution pH and co-existing substrates was firstly reported. It was interestingly found that HA could appreciably accelerate FQs degradation by Mn(VII) at environmentally relevant pH. HA as a reductant in accelerating FQs by Mn(VII) oxidation was distinctly elucidated for the first time, where MnO2 in situ formed from the reduction of Mn(VII) by HA served as a catalyst. Similar products were observed in the presence versus absence of HA. Considering that the accelerating role of HA was related to its reducing ability, an activation method based on Mn(VII) and reductant (i.e., Fe(II), Mn(II) and (bi)sulfite) was proposed, which exhibited considerable potential for application in the treatment of FQs contaminated water.
On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Development of a Highly Efficient Synthesis for Ciprofloxacin
Armstrong, Cameron,Miyai, Yuma,Formosa, Anna,Thomas, Dale,Chen, Esther,Hart, Travis,Schultz, Victor,Desai, Bimbisar K.,Cai, Angela Y.,Almasy, Alexandra,Jensen, Klavs,Rogers, Luke,Roper, Tom
, p. 1524 - 1533 (2021/07/21)
The experimental approach taken and challenges overcome in developing a high-purity production (>100 g) scale process for the telescoped synthesis of the antibiotic ciprofloxacin is outlined. The process was first optimized for each step sequentially with regard to purity and yield, with necessary process changes identified and implemented before scaling for longer runs. These changes included implementing a continuous liquid-liquid extraction (CLLE) step and eliminating and replacing the base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) initially used in the ring-closure step due to DBU plausibly forming a decomposition side product that negatively impacted the final product purity. Process conditions were scaled 1.5-2-fold in order to enable the ultimate project goal of producing enough crude ciprofloxacin within 24 h to manufacture 1000 250 mg tablets. Working toward this goal, several production-scale runs were carried out to assess the reproducibility and robustness of the finalized process conditions, with the first three steps being run continuously up to 22 h and the last two steps being run continuously up to 10 h. The end result is a process with a throughput of ～29 g/h (～700 g/24 h) with a crude product stream profile of 94 ± 2% and 34 ± 3 mg/mL after five chemical transformations across four reactors and one continuous CLLE unit operation with each intermediate step maintaining a purity >95% by HPLC.
PAT Implementation on a Mobile Continuous Pharmaceutical Manufacturing System: Real-Time Process Monitoring with In-Line FTIR and Raman Spectroscopy
Miyai, Yuma,Formosa, Anna,Armstrong, Cameron,Marquardt, Brian,Rogers, Luke,Roper, Thomas
, p. 2707 - 2717 (2021/12/13)
The strategies and experimental methods for implementation of process analytical technology (PAT) on the mobile pharmaceutical manufacturing system, Pharmacy on Demand (PoD), are discussed. With multiple processes to be monitored on the PoD end-to-end continuous manufacturing process, PAT and its real-time process monitoring capability play a significant role in ensuring final product quality. Here, we discuss PAT implementation for real-time monitoring of an intermediate and API concentrations with in-line Fourier-transformed infrared and Raman spectroscopy for the five-step continuous synthesis of ciprofloxacin on the PoD synthesis unit. Two partial least squares regression models were built and verified with flow chemistry experiments to obtain a root-mean-square error of prediction (RMSEP) of 2.2 mg/mL with a relative error of 2.8% for the step 2 FlowIR model and a RMSEP of 0.9 mg/mL with a relative error of 2.8% for the step 5 Raman model. These models were deployed during an 11 h step 1–3 and a 5 h step 4–5 continuous ciprofloxacin synthesis run performed on the PoD system. In these runs, the real-time prediction of intermediate and product concentration was achieved with an online model processing software (Solo_Predictor) and a PAT data collection and management software (synTQ).
