Search Results (97)

An efficient and practical procedure for the synthesis of (E)-α,β-unsaturated amides incorporating α-aminophosphonates, derived from readily accessible phosphonoacetamides, via the Horner–Wadsworth–Emmons (HWE) reaction was developed. The influence of reaction parameters, including base, solvent, and temperature, as well as the scope of the method with different aldehydes, was examined, affording the target compounds in good yields and with high (E)-selectivity. The required phosphonoacetamides were conveniently prepared through a Kabachnik–Fields reaction of aldehydes, benzylamine and dimethyl phosphite followed by hydrogenolytic cleavage of the N-Bn bond, acylation with bromoacetyl bromide, and a subsequent Arbuzov reaction. This HWE protocol provides straightforward access to a broad range of (E)-α,β-unsaturated amides incorporating α-aminophosphonates under mild conditions, offering valuable scaffolds with potential pharmacological relevance as anticancer agents. Full article

Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4⁺, CD4⁺CD25⁺, and CD4⁺CD25⁺FoxP3⁺, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((o-Fph)PPhβCD), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (o-Fph)PPhβCD significantly restored CD4⁺ and CD4⁺CD25⁺ T-cell levels and induced a sustained reduction in regulatory CD4⁺CD25⁺FoxP3⁺ cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (o-Fph)PPhβCD exerted a more prolonged response, which was particularly evident by day 14. Structural confirmation of the inclusion complex was achieved through IR and NMR spectroscopy. These findings highlight (o-Fph)PPhβCD as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation. Full article

Imidazoline I₂ receptors (I₂-IR) are untapped therapeutic targets lacking a structural description. Although the levels of I₂-IR are dysregulated in a plethora of illnesses, the arsenal of ligands that can modulate I₂-IR is limited. In this framework, we have reported several new structural families embodying the iminophosphonate functional group that have an excellent affinity and selectivity for I₂-IR, and selected members have demonstrated relevant pharmacological properties in murine models of neurodegeneration and Alzheimer’s disease. Starting with these iminophosphonates, we continued to exploit their high degree of functionalization through a short and efficient synthesis to access unprecedented 2,3-di, 2,2,3-tri, 2,3,4-tri, and 2,2,3,4-tetrasubstituted diethyl (pyrrolidine-2-yl) phosphonates. The stereochemistry of the new compounds was unequivocally characterized by X-ray crystallographic analyses. Two selected compounds with structural features shared with the starting products were pharmacologically evaluated, allowing us to deduce the required key structural motifs for biologically active aminophosphonate derivatives. Full article

Being overexpressed in many cancer types and related to tumor invasiveness, the activity of P5C reductase represents a promising target for cancer therapy, yet no effective inhibitors have been identified so far. Several phenyl-substituted aminomethylenebisphosphonic acids had been found to inhibit the plant enzyme in the micro- to millimolar range. The two most active compounds were previously shown to be remarkably active against human P5C reductase (PYCR1, gene ID 5831). To investigate their structure–activity relationships, the human enzyme was heterogously expressed in E. coli, affinity purified and assayed in the presence of increasing concentrations of various aminobisphosphonates differing in substituents on the phenyl ring, using either NADH or NADPH as the electron donor. Some analogues, namely aminoethylenebisphosphonates, hydroxybisphosphonates, aminophosphonates and hydroxyphosphonates, were also evaluated. Results allowed to define the chemical features required for effective inhibition. The aminobisphosphonic moiety was found essential for activity, which was enhanced by the presence of electron-withdrawing substituents on the phenyl ring, provided that an optimal steric hindrance is not exceeded. These results could open up new perspectives on the synthesis of effective inhibitors of human P5C reductase to be used in chemotherapy. Full article

In the search for new bioactive molecules, a series of new molecules from the phosphonate family were synthesized via the Kabachnik–Fields reaction (phosphonate ester) and the Irani–Moedritzer reaction (phosphonic acids). Their structures were characterized by various spectroscopic methods, including IR and UV-vis. The synthesized compounds were screened for in vitro antimicrobial activity against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, using the well method. The results also showed that all the products synthesized exhibited good activity with a zone of inhibition: D > 8, except one product against S. aureus bacteria. The three products were tested for their antifungal effects against three pathogenic fungal strains, namely Candida albicans, Aspergillus niger, and Penicillium notatum. The results show that the zones of maximum inhibition were observed against P. notatum (35.5 mm). Therefore, the biological tests showed that all the compounds studied exhibited high antibacterial and antifungal activities. Full article

Bacterial contamination is a major public health concern on a global scale. Treatment resistance in bacterial infections is becoming a significant problem that requires solutions. We were interested in obtaining new polymeric functionalized compounds with antibacterial properties. Three components (polymeric amine, aldehyde, and phosphite) were used in the paper in a modified “one-pot” Kabachnik–Fields reaction, in tetrahydrofuran at 60 °C, to create the N-C-P skeleton in aminophosphonate groups. Two copolymers were thus prepared starting from an acrylonitriledivinylbenzene (AN-15%DVB) copolymer containing pendant primary amine groups modified by grafting aminophosphonate groups, i.e., aminobenzylphosphonate (Bz-DVB-AN) and aminoethylphosphonate (Et-DVB-AN). The two copolymers were characterized by FT-IR spectroscopy, SEM-EDX, TGA, and antibacterial properties. It was shown that the novel products have antibacterial qualities against S. aureus and E. coli bacteria. The sample with the strongest antibacterial activity was Et-DVB-AN. We assessed how well the Weibull model and the first-order kinetic model represent the inactivation of microbial cells in our samples. The main advantage of the new antibacterial agents developed in this work is their easy recovery, which helps to avoid environmental contamination. Full article

The discharge of metal-loaded mining-influenced waters can significantly pollute downstream water bodies for many kilometers. Addressing this issue at the earliest discharge point is crucial to prevent further contamination of the natural environment. Additionally, recovering metals from these discharges and other sources of contamination can reduce the environmental impacts of mining and support the circular economy by providing secondary raw materials. This study focused on optimizing zinc recovery from mining-influenced water in the Freiberg mining region in Germany, where significant loads of zinc are released into the Elbe River. By employing pretreatment techniques, conducting 100 mL scale ion-exchange column experiments, and refining the regeneration process, we aimed to identify optimal conditions for efficient zinc removal and recovery. Initial tests showed that aminophosphonic functionalized TP 260 resin had a high affinity for aluminum, occupying 93% of the resin’s capacity, while zinc capacity was limited to 0.2 eq/L. To improve zinc recovery, selective precipitation of aluminum at pH 6.0 was introduced as a pretreatment step. This significantly increased the zinc loading capacity of the resin to 1 eq/L. Under optimal conditions, a concentrated zinc solution of 18.5 g/L was obtained with 100% recovery. Sulfuric acid proved more effective than hydrochloric acid in eluting zinc from the resin. Further analysis using SEM-EDX revealed residual acid on the resin, indicating a need for additional study on long-term resin performance and capacity variation. The research also highlighted the environmental impact of the Freiberg mining area, where three drainage galleries currently contribute nearly 85 tons of zinc annually to the Elbe River. This study underscores the feasibility of efficient zinc recovery from these point sources of pollution using advanced ion-exchange processes, contributing to circular economy efforts and environmental conservation. Full article

Phosphonates such as ethylenediaminetetra (methylenephosphonic acid) (EDTMP) and aminotris (methylenephosphonic acid) (ATMP) are used every day in water treatment processes or in household products. Their consumption is still increasing, regardless of the debates on their environmental impact. Here, the microbial characterisation and determination of the biodegradation potential of selected industrially relevant phosphonates for the isolate Delftia sp. UMB14 is reported. The opportunistic strain was isolated from a biofilm that was derived from a conventional washing machine using conventional detergents containing phosphonates. In antimicrobial susceptibility testing, the strain was only susceptible to sulfonamide, tetracycline, and chloramphenicol. Physiological and biochemical characteristics were determined using the BIOLOG EcoPlate assay. Most importantly, the strain was shown to convert D-malic acid and D-mannitol, as confirmed for strains of Delftia lacustris, and thus the new isolate could be closely related. Biodegradation tests with different phosphonates showed that the strain preferentially degrades ATMP and EDTMP but does not degrade glyphosate (GS) and amino (methylphosphonic acid) (AMPA). A specific gene amplification confirmed the presence of phnX (phosphonoacetaldehyde hydrolase) and the absence of PhnJ (the gene for the core component of C–P lyase). The presence of PhnCDE is strongly suggested for the strain, as it is common in Delftia lacustris species. Full article

Screen-printed electrodes (SPEs) are reliable, portable, affordable, and versatile electrochemical platforms for the real-time analytical monitoring of emerging analytes in the environmental, clinical, and agricultural fields. The aim of this study was to evaluate the electrochemical behavior of gold screen-printed electrodes (SPGEs) modified with molecules containing amino (Tr-N) or α-aminophosphonate (Tr-P) groups for the selective and sensitive detection of the toxic metal ions Pb²⁺ and Hg²⁺ in aqueous samples. After optimizing the analytical parameters (conditioning potential and time, deposition potential and time, pH and concentration of the supporting electrolyte), anodic square wave stripping voltammetry (SWASV) was used to evaluate and compare the electrochemical performance of bare or modified electrodes for the detection of Hg²⁺ and Pb²⁺, either alone or in their mixtures in the concentration range between 1 nM and 10 nM. A significative improvement in the detection ability of Pb²⁺ ions was recorded for the amino-functionalized gold sensor SPGE-N, while the presence of a phosphonate moiety in SPGE-P led to greater sensitivity towards Hg²⁺ ions. The developed sensors allow the detection of Pb²⁺ and Hg²⁺ with a limit of detection (LOD) of 0.41 nM and 35 pM, respectively, below the legal limits for these heavy metal ions in drinking water or food, while the sensitivity was 5.84 µA nM⁻¹cm⁻² and 10 µA nM⁻¹cm⁻², respectively, for Pb²⁺ and Hg²⁺. The reported results are promising for the development of advanced devices for the in situ and cost-effective monitoring of heavy metals, even in trace amounts, in water resources. Full article

A common issue in studies on liquid-phase chemical processes is that the natural solid nanoimpurities present in reagent-grade chemicals are ignored. Little is known about these impurities’ nature, sizes, concentrations, and behavior, yet they significantly affect the efficiency of antiscalants in municipal and laboratory solutions. Recent research has focused on: (i) estimating nanoimpurity concentrations in in-house deionized water and semiconductor-grade isopropanol using “light sheet” optical ultramicroscopy, and (ii) visualizing antiscalant sorption on these impurities. Using a fluorescent-tagged antiscalant aminobis(methylenephosphonic acid) (ADMP-F), we tracked its affinity to particulate matter in deionized water and reagent-grade KCl solutions. Our study showed that the total concentration of nanoparticles with a size larger than 20 nm is about 10⁶ units/mL in deionized water and 10⁵ units/mL in isopropanol. Extrapolation of these values to a size ≥1 nm resulted in concentrations of 10¹¹ and 10⁸ units/mL. The addition of KCl or ADMP-F significantly increased foreign nanoparticle populations. ADMP-F is selectively adsorbed by only some impurities, while most antiscalant molecules remain as true solution. To our knowledge, this is the first instance of fluorescently labeled aminoalkylphosphonates being able to differentiate particulate matter traces in reagent-grade purity solutions. Therefore, the role of nanoparticles as crystallization centers should be seriously reconsidered, especially in their important application in scale inhibition. Full article

In order to overcome the interface emulsification problem of TBP-FeCl₃ systems and the instability of β-diketone systems in high-concentration alkaline medium, it is necessary to design and synthesize some new extractants. By introducing amino groups into a phosphorus extractant, a new 2-ethylhexyl hydrogen {[bis(2-ethylhexyl)amino]methyl} phosphonate acid (HA) extractant was synthesized. In this study, an efficient method of recovering lithium from the effluent of spent lithium-ion batteries (LIBs) is proposed. Experiments were conducted to assess the influential factors in lithium recovery, including the solution pH, saponification degree, extractant concentration, and phase ratio. Over 95% of lithium in the effluent was extracted into the organic phase, and nearly all lithium in the organic phase could be stripped into the aqueous phase using a 3 mol/L HCl solution. There was no significant decrease in extraction capacity after 10 cycles. The experimental results indicated that the extraction mechanism was a cation exchange process, and the extractive complex was proposed as LiA. Importantly, after three months of stable operation, the process demonstrated excellent stability and extraction efficiency, with rapid phase separation and a clear interface. This study offers an efficient, cost-effective, and environmentally friendly method for lithium extraction from the effluent of spent LIBs. Full article

In this research, we explore the synthesis of and characterize α-aminophosphonates derived from anthraquinone and benzanthrone, focusing on their fluorescence properties and potential applications in confocal laser scanning microscopy (CLSM). The synthesized compounds exhibit notable solvatochromic behavior, emitting fluorescence from green to red across various solvents. Spectroscopic analysis, including ¹H-, ¹³C-, and ³¹P-NMR, FTIR, and mass spectrometry, confirms the chemical structures. The compounds’ toxicity is evaluated using etiolated wheat sprouts, revealing varying degrees of impact on growth and oxidative damage. Furthermore, the study introduces these α-aminophosphonates for CLSM imaging of the parasitic flatworm Opisthorchis felineus, demonstrating their potential in visualizing biological specimens. Additionally, an X-ray crystallographic study of an anthraquinone α-aminophosphonate provides valuable structural insights. Full article

Recently, multicomponent reactions (MCRs) have attracted much attention in polymer synthesis. As one of the most well-known MCRs, the Kabachnik–Fields (KF) reaction has been widely used in the development of new functional polymers. The KF reaction can efficiently introduce functional groups into polymer structures; thus, polymers prepared via the KF reaction have unique α-aminophosphonates and show important bioactivity, metal chelating abilities, and flame-retardant properties. In this mini-review, we mainly summarize the latest advances in the KF reaction to synthesize functional polymers for the preparation of heavy metal adsorbents, multifunctional hydrogels, flame retardants, and bioimaging probes. We also discuss some emerging applications of functional polymers prepared by means of the KF reaction. Finally, we put forward our perspectives on the further development of the KF reaction in polymer chemistry. Full article

Valorphin (V1) is a naturally occurring peptide derived from hemoglobin that has been found to have an affinity for opioid receptors and exhibits antinociceptive and anticonvulsant activity. Some of its synthetic analogs containing an aminophosphonate moiety show structure-dependent potent antinociceptive effects. This study aimed to reveal a detailed picture of the antinociceptive mechanisms and behavioral effects of V1 and its recently synthesized phosphopeptide analog V2p in rodents using a range of methods. The studied peptides significantly reduced acute (mean V1–9.0, V2p–5.8 vs. controls–54.1 s) and inflammatory (mean V1–57.9 and V2p–53.3 vs. controls–107.6 s) nociceptive pain in the formalin test, as well as carrageenan-induced hyperalgesia (mean V1–184.7 and V2p–107.3 vs. controls–61.8 g) in the paw pressure test. These effects are mediated by activation of opioid receptors with a predominance of kappa in V1 antinociception and by delta, kappa, and mu receptors in V2p-induced antinociception. Both peptides did not change the levels of TNF-alpha and IL-1-beta in blood serum. V1 induces depression-like behavior, and V2p shows a tendency toward anxiolysis and short-term impairment of motor coordination without affecting exploratory behavior. The results characterize valorphin and its derivative as promising analgesics that exert their effects both centrally and peripherally, without causing severe behavioral changes in experimental animals. These encouraging data are a foundation for future studies focusing on the effects of hemorphins after long-term treatment. Full article

The purpose of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity against selected strains of multidrug-resistant nosocomial pathogenic bacteria. The previously developed enzyme-catalysed Kabachnik–Fields protocol allowed us to obtain the studied compounds with high yields which were free from metal impurities. The structure–activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF₃−) in the coumarin scaffold. MIC and MBC studies carried out on six selected pathogenic bacterial strains (Gram-positive pathogenic Staphylococcus aureus (ATCC 23235) strain, as well as on Gram-negative Acinetobacter baumannii (ATCC 17978), Pseudomonas aeruginosa (ATCC 15442), Enterobacter cloacae (ATCC 49141), Porphyromonas gingivalis (ATCC 33277), and Treponema denticola (ATCC 35405)) have shown that tested compounds show a strong bactericidal effect at low concentrations. Among all agents investigated, five exhibit higher antimicrobial activity than those observed for commonly used antibiotics. It should be noted that all the compounds tested showed very high activity against S. aureus, which is the main source of nosocomial infections that cause numerous fatalities. Furthermore, we have shown that the studied coumarin-based α-aminophosphonates, depending on their structural characteristics, are non-selective and act efficiently against various Gram-positive and Gram-negative pathogens, which is of great importance for hospitalised patients. Full article