Identifying urotropine derivatives as co-donors of formaldehyde and nitric oxide for improving antitumor therapy.

A pharmacophore integration strategy was utilized to develop the first co-donor of formaldehyde and nitric oxide (FANO), composed of urotropine derived nitramine/nitrosamine. FANO simultaneously generated formaldehyde and nitric oxide on-demand, resulting in synergistic anticancer effects. Importantly, liposomal formulation of FANO effectively inhibited tumor growth with minimal side-effects, providing a potent combined nitric oxide therapy for malignancy.

The Production and Potential Detection of Hexamethylenetetramine-Methanol in Space.

Numerous laboratory studies of astrophysical ice analogues have shown that their exposure to ionizing radiation leads to the production of large numbers of new, more complex compounds, many of which are of astrobiological interest. We show here that the irradiation of astrophysical ice analogues containing H2O, CH3OH, CO, and NH3 yields quantities of hexamethylenetetramine-methanol (hereafter HMT-methanol; C7N4H14O) that are easily detectible in the resulting organic residues. This molecule differs from simple HMT, which is known to be abundant in similar ice photolysis residues, by the replacement of a peripheral H atom with a CH2OH group. As with HMT, HMT-methanol is likely to be an amino acid precursor. HMT has tetrahedral (Td) symmetry, whereas HMT-methanol has C1 symmetry. We report the computed expected infrared spectra for HMT and HMT-methanol obtained using ab initio quantum chemistry methods and show that there is a good match between the observed and computed spectra for regular HMT. Since HMT-methanol lacks the high symmetry of HMT, it produces rotational transitions that could be observed at longer wavelengths, although establishing the exact positions of these transitions may be challenging. It is likely that HMT-methanol represents an abundant member of a larger family of functionalized HMT molecules that may be present in cold astrophysical environments.

Green protocol for the preparation of hydrophilic molecularly imprinted resin in water for the efficient selective extraction and determination of plant hormones from bean sprouts.

In this study, a novel and green synthesis of a new hydrophilic molecularly imprinted 3-aminophenol-hexamethylenetetramine (MIAPH) resin for the selective recognition and separation of plant hormones was developed. The MIAPH resin was obtained using 3-aminophenol as multifunctional monomer which introduced hydroxyl, amino, and imino groups simultaneously, and adenine was used as a dummy template for molecular imprinting. Meanwhile, hexamethylenetetramine released formaldehyde slowly through hydrolysis which was used as the cross-linking agent to avoid the direct and excessive use of toxic formaldehyde. The entire procedure was performed under mild conditions, and was facile, environmentally friendly and energy-efficient. The obtained MIAPH resin showed high specific recognition toward plant hormones and higher recoveries in bean sprouts compared to NIAPH, HLB, and C18. Various parameters affecting the extraction efficiency were optimized, and the calibration linearity of the MIAPH‒SPE‒HPLC method was determined from 0.07 to 2.86 mg kg-1 with a correlation coefficient (r) ≥ 0.9994 under the optimal conditions. Recoveries of spiked standards ranged from 90.2 to 99.1% for bean sprout with a relative standard deviation of ≤5.3%. Finally, the established MIAPH‒SPE‒HPLC method was successfully applied for the selective extraction and sensitive detection of plant hormones in a variety of complex vegetable matrices.

High-efficacy adsorption of Cr(VI) and anionic dyes onto ß-cyclodextrin/chitosan/hexamethylenetetramine aerogel beads with task-specific, integrated components.

To significantly enhance the adsorption efficacy of hexavalent chromium from aqueous medium, a novel and non-toxic chitosan-based composite beads were prepared by integrating task-specific components into one sample, namely ß-cyclodextrin/chitosan/hexamethylenetetramine (ß-CD-CS@HMTA). The pseudo- second-order kinetic and Langmuir isotherm model was used to describe the adsorption process. The maximum capacity Cr(VI) removal reached 333.8 mg/g which was superior to most of reported CS derivative adsorbents. The sorption mechanism of composite was investigated by employing FT-IR, SEM-EDS and XPS techniques. It showed that the reason for efficient removal of Cr(VI) onto resultant sample including chemisorption and reduction of Cr(VI) to the non-toxic Cr(III), and the two components of ß-CD and HMTA with task-specific had played a crucial role during the adsorption process. Most importantly, for fixed-bed column sorption testing, the breakthrough curves were well fitted by Thomas model under different flow rates (1, 2 and 3 mL/min). Moreover, the ß-CD-CS@HMTA had also manifested perfect adsorption capability towards anionic dyes in initial concentration 500 mg/L. This research indicated that as-fabricated chitosan-based composite beads are promising adsorbents for Cr(VI) and anionic dyes because of its superiority of low-cost, easy regeneration and environmental friendly.

Formaldehyde Release From Personal Care Products: Chromotropic Acid Method Analysis.

BACKGROUND: Preservatives such as formaldehyde and formaldehyde releasers (F/FRs) are found in personal care products. Studies from Europe and Israel have indicated that products with undeclared F/FRs on product labels may have detectable levels of formaldehyde. OBJECTIVE: The aim of the study was to determine the presence of formaldehyde in samples of US personal care products. METHODS: Fifty-four baby and adult products were tested with the chromotropic acid method. A blinded investigator graded the color change as mild, moderate, or strong. RESULTS: All 8 products declaring F/FRs resulted in a deep purple color change, indicating a strong reaction. Of the 46 products with undeclared F/FRs, 4 (8.6%) were found to release formaldehyde. All 4 resulted in a light purple color change, indicating a mild reaction. CONCLUSIONS: Overall, 4 of 54 products (7.4%) had label information, which did not match chromotropic acid method testing results. Clinicians and formaldehyde-allergic individuals should be aware of the limitations of product ingredient labeling in managing allergic contact dermatitis to formaldehyde.

Improved corrosion resistance of commercially pure magnesium after its modification by plasma electrolytic oxidation with organic additives.

The optimal mechanical properties render magnesium widely used in industrial and biomedical applications. However, magnesium is highly reactive and unstable in aqueous solutions, which can be modulated to increase stability of reactive metals that include the use of alloys or by altering the surface with coatings. Plasma electrolytic oxidation is an efficient and tuneable method to apply a surface coating. By varying the plasma electrolytic oxidation parameters voltage, current density, time and (additives in the) electrolytic solution, the morphology, composition and surface energy of surface coatings are set. In the present study, we evaluated the influence on surface coatings of two solute additives, i.e. hexamethylenetetramine and mannitol, to base solutes silicate and potassium hydroxide. Results from in vitro studies in NaCl demonstrated an improvement in the corrosion resistance. In addition, coatings were obtained by a two-step anodization procedure, firstly anodizing in an electrolyte solution containing sodium fluoride and secondly in an electrolyte solution with hexamethylenetetramine and mannitol, respectively. Results showed that the first layer acts as a protective layer which improves the corrosion resistance in comparison with the samples with a single anodizing step. In conclusion, these coatings are promising candidates to be used in biomedical applications in particular because the components are non-toxic for the body and the rate of degradation of the surface coating is lower than that of pure magnesium.

Carbon fiber paper@MgO films: in situ fabrication and high-performance removal capacity for phosphate anions.

Porous magnesium oxide (MgO) films on carbon fiber paper (CF) have been successfully fabricated in a hydrothermal route at different calcination temperatures. The CF@MgO samples (CF@MgO-300, -400, and -500) show different morphologies with the increasing surface area from 3 for CF to 27 m2 g-1 for CF@MgO-400. Among the four investigated samples, the CF@MgO-400 exhibits the highest phosphate removal ability (~ 1230 mg g-1) with promising applications for the large-scale utilization at low cost.

A pH-sensitive methenamine mandelate-loaded nanoparticle induces DNA damage and apoptosis of cancer cells.

Methenamine mandelate is a urinary antibacterial agent, which can be converted to formaldehyde in urine that has a relatively low pH of average 5.5-6.8. Here, we prepare a pH-sensitive PLGA-based nanoparticle containing both methenamine mandelate and NaHCO3. Methenamine mandelate/NaHCO3-coloaded nanoparticle could enter cells via endosome/lysosome pathway. The pH in lysosomes and endo-lysosomes is approximately 5.0. In the acidic environment, NaHCO3 reacts with proton and produce CO2 bubbles, which burst nanoparticles and lead to the rapidly release of methenamine mandelate. Meanwhile, methenamine mandelate was then quickly converted to a sufficient amount of formaldehyde in this acidic environment, which induced DNA damage and DNA damage response (DDR). Consequently, methenamine mandelate/NaHCO3-coloaded nanoparticles caused cell cycle arrest, cell growth inhibition and apoptosis of cancer cells. Moreover, methenamine mandelate/NaHCO3-coloaded nanoparticles also show intensive inhibitory effect on the growth of MCF-7 xenograft tumor in vivo. Therefore, methenamine mandelate/NaHCO3-coloaded nanoparticle is a promising type of formulation for the treatment of cancer, which could give the "old drug" methenamine mandelate a new anti-cancer function in clinical. STATEMENT OF SIGNIFICANCE: Methenamine mandelate is a urinary antibacterial agent, which can be converted to formaldehyde in urine that has a relatively low pH of average 5.5-6.8. Here, we prepare a pH-sensitive PLGA-based nanoparticle containing both methenamine mandelate and NaHCO3. Methenamine mandelate/NaHCO3-coloaded nanoparticle could enter cells via endosome/lysosome pathway. The pH in lysosomes and endo-lysosomes is approximately 5.0. In the acidic environment, NaHCO3 reacts with proton and produce CO2 bubbles, which burst nanoparticles and lead to the rapidly release of methenamine mandelate. Meanwhile, methenamine mandelate was then quickly converted to a sufficient amount of formaldehyde in this acidic environment, which induced DNA damage and DNA damage response (DDR). Methenamine mandelate/NaHCO3-coloaded nanoparticle is a promising type formulation for the treatment of cancer, which could give the "old drug" methenamine mandelate a new anti-cancer function in clinical.

Integrated biological and advanced oxidation based treatment of hexamine bearing wastewater: Effect of cow-dung as a co-substrate.

This work examines the treatment of hexamethylenetetramine (HMT) bearing effluent from N, N-dinitroso pentamethylene tetra-mine producing industrial plants in India. Chemical treatment using Fenton's reagent and aerobic treatment using batch reactors with co-substrate were investigated. Aerobic batch reactors integrated with advanced oxidation process of Fenton's reagent provides effective treatment of HMT effluents. Influence of Fenton's reagent dose reaction/contact and effect of varying co-substrate with effluent initial concentration was observed. Higher dose 100 mL of Fenton's reagent with higher reaction time 20 h resulted better degradation (34.88%) of wastewater. HMT hydrolyzes in acidic environment to ammonia and formaldehyde. Formaldehyde under normal conditions is toxic for biological treatment processes. When hydrolysis and acidification in the reactors are accompanied by low pH, aerobic batch reactors with use of co-substrates glucose, sucrose, and cow-dung extract separately in different proportion to wastewater ranging from 0.67 to 4.00, degraded wastewater effectively. Higher proportion of co-substrate to wastewater resulted better degradation. The relationships between nitrate, pH, turbidity and COD are discussed.

A two-photon probe for Al(3+) in aqueous solution and its application in bioimaging.

A salicylimine probe L with a simple structure has been researched more in-depth on fluorescence sensor properties based on two-photon (TP) absorption. L displays excellent selective turn-on fluorescence response for Al(3+) in hexamethylenetetramine-buffered (HMTA) aqueous solution (0.3M, pH=5.8) under one-photon (OP) excitation. With the help of OP fluorescence, TP fluorescence titration, UV-spectra titration and Job's plot, the stoichiometric ratio of L with Al(3+) was determined to be 1:1. The coordination sites and the coordination mechanism of L with Al(3+) were analyzed in detail through (1)H NMR data. Not only with a detection limit of 5.2×10(-9)M in vitro, but also the probe has been successfully used in the live cells and tissues for the imaging of Al(3+) with TP fluorescence microscopy due to the enlarged TP cross section, providing a novel testing method for measuring Al(3+) in solution or cell tissue with low autofluorescence and cytotoxicity.

Factors affecting total dissolved solids concentration of γ-ray-irradiated aqueous hexamethylenetetramine solution: a dosimetric study.

A new γ-ray-radiation dosimetric system (TDS-HMTA), comprising a 'total dissolved solids (TDS)' meter and 0.02 M aqueous hexamethylenetetramine (HMTA) solution, is introduced for medical and biological applications. Gamma-ray radiolysis of aqueous HTMA solutions increases the concentrations (ppm) of TDS, which is measured by the TDS meter. The effects of HMTA concentration, absorbed radiation dose, absorbed dose rate, and storage time on the TDS concentration of irradiated HMTA solutions were studied. It was found that 0.02 M aqueous HMTA solution yields the highest sensitivity to γ-ray-radiation according to TDS concentration measurements. The effect of absorbed radiation dose was studied in the range 1.64-435.5 kGy. The TDS concentration increases linearly up to the maximum of the studied absorbed radiation dose range (R(2) = 0.9965). The overall coefficient of variation (CV %) associated with TDS concentration measurements of 0.02 M HMTA solution as a function of absorbed dose was found to be 0.732%. The effect of dose rate on the TDS concentration was studied in the range 0.33-3.31 kGy/h. It was found, also, that the TDS concentration is relatively stable over a storage period of 144 h after irradiation with different doses. The tissue equivalency of 0.02 M aqueous HMTA solutions allow it to be used for radiation dose measurement during sterilization in human tissue banks. Therefore, this system (TDS-HMTA) could be considered as a promising candidate for γ-ray radiation dosimetry in technical, medical and research fields.

Determination of hexamethylenetetramine in foods by high-performance liquid chromatography (HPLC).

A simple and rapid method was developed and validated for the determination of hexamethylenetetramine (HMT) in foods. Samples were homogenised and extracted with methanol, followed by centrifugation. The resulting solution was filtered and injected into the high-performance liquid chromatograph (HPLC). HMT was separated using a Zorbax SCX-300 column coupled to a photodiode array detector. The calibration curve was linear in the range of 1.0-100 µg ml(-1), with good correlation coefficients (r(2) = 0.9992). The recoveries of HMT from foods spiked at levels of 10, 50 and 100 mg kg(-1) ranged from 91.6% to 103.8%, with relative standard deviations (RSDs) between 0.9% and 5.3%. The limit of detection and the limit of quantification of HMT were 0.3 and 1.0 mg kg(-1) based on three food matrixes (provolone cheese, glass noodle and tofu snack), respectively. Uncertainty associated with accuracy contributed mostly to the expanded uncertainty. No detectable levels of HMT were found in any of the samples retailed in Korea. The method was successful in determining HMT in foods.

Non linear optical analyses of hexamine: phenol cocrystals based on hydrogen bonding: a comparative study.

Fourier-Transform Infrared (FT-IR) spectroscopy supported by Raman spectroscopy has been employed to explain the conventional and unconventional hydrogen bonding present in the 4,4'thiodiphenol: hexamine and 4,4'sulfonyldiphenol: hexamine cocrystals. The possible internal and external vibrational modes are predicted through factor group analysis. Influence of intra molecular charge transfer (ICT) interaction caused by the strong ionic ground state hydrogen bonding between charged species, giving rise to a non centro symmetric structure which is a criterion for second harmonic generation (SHG) efficiency has been discussed. Intense low wave number hydrogen bond vibrations in Raman which arise due to electron-phonon coupling are analyzed. Optical quality of adducts is identified through UV-Vis analysis. The second harmonic generation efficiency of both adducts is determined by Kurtz-Perry method.

Towards high-performance, low-cost quartz sensors with high-density, well-separated, vertically aligned ZnO nanowires by low-temperature, seed-less, single-step, double-sided growth.

Resonant sensors with nanostructured surfaces have long been considered as an emergent platform for high-sensitivity transduction because of the potentially very large sensing areas. Nevertheless, until now only complex, time-consuming, expensive and sub-optimal fabrication procedures have been described; in fact, especially with reference to in-liquid applications, very few devices have been reported. Here, we first demonstrate that, by immersing standard, ultra-low-cost quartz resonators with un-polished silver electrodes in a conventional zinc nitrate/HMTA equimolar nutrient solution, the gentle contamination from the metallic package allows direct growth on the electrodes of arrays of high-density (up to 10 µm⁻²) and well-separated (no fusion at the roots) ZnO nanowires without any seed layer or thermal annealing. The combination of high-density and good separation is ideal for increasing the sensing area; moreover, this uniquely simple, single-step process is suitable for conventional, ultra-low-cost and high-frequency quartzes, and results in devices that are already packaged and ready to use. As an additional advantage, the process parameters can be effectively optimized by measuring the quartz admittance before and after growth. As a preliminary test, we show that the sensitivity to the liquid properties of high-frequency (i.e. high sensitivity) quartzes can be further increased by nearly one order of magnitude and thus show the highest ever reported frequency shifts of an admittance resonance in response to immersion in both ethanol and water.

Concise NMR approach for molecular dynamics characterizations in organic solids.

Molecular dynamics characterisations in solids can be carried out selectively using dipolar-dephasing experiments. Here we show that the introduction of a sum of Lorentzian and Gaussian functions greatly improve fittings of the "intensity versus time" data for protonated carbons in dipolar-dephasing experiments. The Lorentzian term accounts for remote intra- and intermolecular (1)H-(13)C dipole-dipole interactions, which vary from one molecule to another or for different carbons within the same molecule. Thus, by separating contributions from weak remote interactions, more accurate Gaussian decay constants, T(dd), can be extracted for directly bonded (1)H-(13)C dipole-dipole interactions. Reorientations of the (1)H-(13)C bonds lead to the increase of T(dd), and by measuring dipolar-dephasing constants, insight can be gained into dynamics in solids. We have demonstrated advantages of the method using comparative dynamics studies in the α and γ polymorphs of glycine, cyclic amino acids L-proline, DL-proline and trans-4-hydroxy-L-proline, the Ala residue in different dipeptides, as well as adamantane and hexamethylenetetramine. It was possible to distinguish subtle differences in dynamics of different carbon sites within a molecule in polymorphs and in L- and DL-forms. The presence of overall molecular motions is shown to lead to particularly large differences in dipolar-dephasing experiments. The differences in dynamics can be attributed to differences in noncovalent interactions. In the case of hexamethylenetetramine, for example, the presence of C-H···N interactions leads to nearly rigid molecules. Overall, the method allows one to gain insight into the role of noncovalent interactions in solids and their influence on the molecular dynamics.

Cellular interaction and toxicity depend on physicochemical properties and surface modification of redox-active nanomaterials.

The study of the chemical and biological properties of CeO2 nanoparticles (CNPs) has expanded recently due to its therapeutic potential, and the methods used to synthesize these materials are diverse. Moreover, conflicting reports exist regarding the toxicity of CNPs. To help resolve these discrepancies, we must first determine whether CNPs made by different methods are similar or different in their physicochemical and catalytic properties. In this paper, we have synthesized several forms of CNPs using identical precursors through a wet chemical process but using different oxidizer/reducer; H2O2 (CNP1), NH4OH (CNP2), or hexamethylenetetramine (HMT-CNP1). Physicochemical properties of these CNPs were extensively studied and found to be different depending on the preparation methods. Unlike CNP1 and CNP2, HMT-CNP1 was readily taken into endothelial cells and the aggregation can be visualized using light microscopy. Exposure to HMT-CNP1 also reduced cell viability at a 10-fold lower concentration than CNP1 or CNP2. Surprisingly, exposure to HMT-CNP1 led to substantial decreases in ATP levels. Mechanistic studies revealed that HMT-CNP1 exhibited substantial ATPase (phosphatase) activity. Though CNP2 also exhibits ATPase activity, CNP1 lacked ATPase activity. The difference in catalytic (ATPase) activity of different CNPs preparation may be due to differences in their morphology and oxygen extraction energy. These results suggest that the combination of increased uptake and ATPase activity of HMT-CNP1 may underlie the biomechanism of the toxicity of this preparation of CNPs and may suggest that ATPase activity should be considered when synthesizing CNPs for use in biomedical applications.

Helical structure determines different susceptibilities of dsDNA, dsRNA, and tsDNA to counterion-induced condensation.

Recent studies of counterion-induced condensation of nucleic acid helices into aggregates produced several puzzling observations. For instance, trivalent cobalt hexamine ions condensed double-stranded (ds) DNA oligomers but not their more highly charged dsRNA counterparts. Divalent alkaline earth metal ions condensed triple-stranded (ts) DNA oligomers but not dsDNA. Here we show that these counterintuitive experimental results can be rationalized within the electrostatic zipper model of interactions between molecules with helical charge motifs. We report statistical mechanical calculations that reveal dramatic and nontrivial interplay between the effects of helical structure and thermal fluctuations on electrostatic interaction between oligomeric nucleic acids. Combining predictions for oligomeric and much longer helices, we also interpret recent experimental studies of the role of counterion charge, structure, and chemistry. We argue that an electrostatic zipper attraction might be a major or even dominant force in nucleic acid condensation.

Quaternary ammonium-functionalized silica sorbents for the solid-phase extraction of aromatic amines under normal phase conditions.

Quaternary ammonium-functionalized silica materials were synthesized and applied for solid-phase extraction (SPE) of aromatic amines, which are classified as priority pollutants by US Environmental Protection Agency. Hexamethylenetetramine used for silica surface modification for the first time was employed as SPE sorbent under normal phase conditions. Hexaminium-functionalized silica demonstrated excellent extraction efficiencies for o-toluidine, 4-ethylaniline and quinoline (recoveries 101-107%), while for N,N-dimethylaniline and N-isopropylaniline recoveries were from low to moderate (14-46%). In addition, the suitability of 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica as SPE sorbent was tested under normal phase conditions. The recoveries achieved for the five aromatic amines ranged from 89 to 99%. The stability of the sorbent was evaluated during and after 150 extractions. Coefficients of variation between 4.5 and 10.2% proved a high stability of the synthesized sorbent. Elution was carried out using acetonitrile in the case of hexaminium-functionalized silica and water for 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica sorbent. After the extraction the analytes were separated and detected by liquid chromatography ultraviolet detection (LC-UV). The retention mechanism of the materials was primarily based on polar hydrogen bonding and π-π interactions. Comparison made with activated silica proved the quaternary ammonium-functionalized materials to offer different selectivity and better extraction efficiencies for aromatic amines. Finally, 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica sorbent was successfully tested for the extraction of wastewater and soil samples.