Dual mechanisms of HNO generation by a nitroxyl prodrug of the diazeniumdiolate (NONOate) class

Here we describe a novel caged form of the highly reactive bioeffector molecule, nitroxyl (HNO). Reacting the labile nitric oxide (NO)- and HNO-generating salt of structure iPrHN-N(O)═NO(-)Na(+) (1, IPA/NO) with BrCH(2)OAc produced a stable derivative of structure iPrHN-N(O)═NO-CH(2)OAc (2, AcOM-IPA/NO), which hydrolyzed an order of magnitude more slowly than 1 at pH 7.4 and 37 °C. Hydrolysis of 2 to generate HNO proceeded by at least two mechanisms. In the presence of esterase, straightforward dissociation to acetate, formaldehyde, and 1 was the dominant path. In the absence of enzyme, free 1 was not observed as an intermediate and the ratio of NO to HNO among the products approached zero. To account for this surprising result, we propose a mechanism in which base-induced removal of the N-H proton of 2 leads to acetyl group migration from oxygen to the neighboring nitrogen, followed by cleavage of the resulting rearrangement product to isopropanediazoate ion and the known HNO precursor, CH(3)-C(O)-NO. The trappable yield of HNO from 2 was significantly enhanced over 1 at physiological pH, in part because the slower rate of hydrolysis for 2 generated a correspondingly lower steady-state concentration of HNO, thus, minimizing self-consumption and enhancing trapping by biological targets such as metmyoglobin and glutathione. Consistent with the chemical trapping efficiency data, micromolar concentrations of prodrug 2 displayed significantly more potent sarcomere shortening effects relative to 1 on ventricular myocytes isolated from wild-type mouse hearts, suggesting that 2 may be a promising lead compound for the development of heart failure therapies.     

Development and validation of an integrated computational approach for the modeling of cw-ESR spectra of free radicals in solution: p-(methylthio)phenyl nitronylnitroxide in toluene as a case study

In this work we address the interpretation, via an ab initio integrated computational approach, of continuous wave electron spin resonance (cw-ESR) spectra of p-(methylthio)phenyl nitronylnitroxide (MTPNN) dissolved in toluene. Our approach is based on the determination of the spin Hamiltonian, averaged with respect to fast vibrational motions, with magnetic tensor parameters (Zeeman and hyperfine tensors) characterized by quantum mechanical density functional calculations. The system is then described by a stochastic Liouville equation, with inclusion of diffusive rotational dynamics. Parametrization of diffusion rotational tensor is provided by a hydrodynamic model. Cw-ESR spectra of MTPNN are simulated for a wide range of temperatures (155-292 K) with minimal resorting to fitting procedures, proving that the combination of sensitive ESR spectroscopy and sophisticated modeling can be highly helpful in providing structural and dynamic information on molecular systems.     

Antioxidant,Anti-Inflammatory,and Inhibition of Acetylcholinesterase Potentials of Cassia timoriensis DC. Flowers

Despite being widely used traditionally as a general tonic, especially in South East Asia, scientific research on Cassia timoriensis, remains scarce. In this study, the aim was to evaluate the in vitro activities for acetylcholinesterase (AChE) inhibitory potential, radical scavenging ability, and the anti-inflammatory properties of different extracts of C. timoriensis flowers using Ellman’s assay, a DPPH assay, and an albumin denaturation assay, respectively. With the exception of the acetylcholinesterase activity, to the best of our knowledge, these activities were reported for the first time for C. timoriensis flowers. The phytochemical analysis confirmed the existence of tannins, flavonoids, saponins, terpenoids, and steroids in the C. timoriensis flower extracts. The ethyl acetate extract possessed the highest phenolic and flavonoid contents (527.43 ± 5.83 mg GAE/g DW and 851.83 ± 10.08 mg QE/g DW, respectively) as compared to the other extracts. In addition, the ethyl acetate and methanol extracts exhibited the highest antioxidant (IC₅₀ 20.12 ± 0.12 and 34.48 ± 0.07 µg/mL, respectively), anti-inflammatory (92.50 ± 1.38 and 92.22 ± 1.09, respectively), and anti-AChE (IC₅₀ 6.91 ± 0.38 and 6.40 ± 0.27 µg/mL, respectively) activities. These results suggest that ethyl acetate and methanol extracts may contain bioactive compounds that can control neurodegenerative disorders, including Alzheimer’s disease, through high antioxidant, anti-inflammatory, and anti-AChE activities.     

Three New Pentacyclic Triterpenoids from Lantana camara

Three new pentacyclic triterpenes ursoxy acid ( 1 ), methyl ursoxylate ( 2 ), and ursangilic acid ( 3 ), along with three known compounds dotriacontanoic acid, oleanolic acid acetate, and tetracosanoic acid, were isolated from the aerial parts of Lantana camara Linn . Structures of the new compounds were elucidated by chemical transformation and spectral studies including 1D (¹H‐ and ¹³C‐NMR) and 2D (COSY‐45, NOESY, J‐resolved, HMQC, and HMBC) NMR spectroscopy.     

Long-Term Colloidally Stable Aqueous Dispersions of ≤5 nm Spinel Ferrite Nanoparticles

Applications in biomedicine and ferrofluids, for instance, require long-term colloidally stable, concentrated aqueous dispersions of magnetic, biocompatible nanoparticles. Iron oxide and related spinel ferrite nanoparticles stabilized with organic molecules allow fine-tuning of magnetic properties via cation substitution and water-dispersibility. Here, we synthesize≤5 nm iron oxide and spinel ferrite nanoparticles, capped with citrate, betaine and phosphocholine, in a one-pot strategy. We present a robust approach combining elemental (CHN) and thermal gravimetric analysis (TGA) to quantify the ratio of residual solvent molecules and organic stabilizers on the particle surface, being of particular accuracy for ligands with heteroatoms compared to the solvent. SAXS experiments demonstrate the long-term colloidal stability of our aqueous iron oxide and spinel ferrite nanoparticle dispersions for at least 3 months. By the use of SAXS we approved directly the colloidal stability of the nanoparticle dispersions for high concentrations up to 100 g L⁻¹.     

A Gas Chromatography‐Molecular Rotational Resonance Spectroscopy Based System of Singular Specificity

We designed and demonstrated the unique abilities of the first gas chromatography–molecular rotational resonance spectrometer (GC‐MRR). While broadly and routinely applicable, its capabilities can exceed those of high‐resolution MS and NMR spectroscopy in terms of selectivity, resolution, and compound identification. A series of 24 isotopologues and isotopomers of five organic compounds are separated, identified, and quantified in a single run. Natural isotopic abundances of mixtures of compounds containing chlorine, bromine, and sulfur heteroatoms are easily determined. MRR detection provides the added high specificity for these selective gas‐phase separations. GC‐MRR is shown to be ideal for compound‐specific isotope analysis (CSIA). Different bacterial cultures and groundwater were shown to have contrasting isotopic selectivities for common organic compounds. The ease of such GC‐MRR measurements may initiate a new era in biosynthetic/degradation and geochemical isotopic compound studies.     

Phenolics, flavonoids, antioxidant activity and cyanogenic glycosides of organic and mineral-base fertilized cassava tubers

A field study was conducted to determine the effect of organic and mineral-based fertilizers on phytochemical contents in the tubers of two cassava varieties. Treatments were arranged in a split plot design with three replicates. The main plot was fertilizer source (vermicompost, empty fruit bunch compost and inorganic fertilizer) and sub-plot was cassava variety (Medan and Sri Pontian). The amount of fertilizer applied was based on 180 kg K(2)O ha-1. The tubers were harvested and analyzed for total flavonoids, total phenolics, antioxidant activity and cyanogenic glucoside content. Total phenolic and flavonoid compounds were determined using the Folin-Ciocalteu assay and aluminium chloride colorimetric method, respectively. Different sources of fertilizer, varieties and their interactions were found to have a significant effect on phytochemical content. The phenolic and flavonoid content were significantly higher (p < 0.01) in the vermicompost treatment compared to mineral fertilizer and EFB compost. The total flavonoids and phenolics content of vermicompost treated plants were 39% and 38% higher, respectively, than those chemically fertilized. The antioxidant activity determined using the DPPH and FRAP assays were high with application of organic fertilizer. Cyanogenic glycoside levels were decreased with the application of organic fertilizer. Among the two types of compost, vermicompost resulted in higher nutritional value of cassava tubers. Medan variety with application of vermicompost showed the most promising nutritional quality. Since the nutritional quality of cassava can be improved by organic fertilization, organic fertilizer should be used in place of chemical fertilizer for environmentally sustainable production of better quality cassava.     

Quadratic nonlinearity of one- and two-electron oxidized metalloporphyrins and their switching in solution

We report the quadratic nonlinearity of one- and two-electron oxidation products of the first series of transition metal complexes of meso-tetraphenylporphyrin (TPP). Among many MTPP complexes, only CuTPP and ZnTPP show reversible oxidation/reduction cycles as seen from cyclic voltammetry experiments. While centrosymmetric neutral metalloporphyrins have zero first hyperpolarizability, beta, as expected, the cation radicals and dications of CuTPP and ZnTPP have very high beta values. The one- and two-electron oxidation of the MTPPs leads to symmetry-breaking of the metal-porphyrin core, resulting in a large beta value that is perhaps aided in part by contributions from the two-photon resonance enhancement. The calculated static first hyperpolarizabilities, beta0, which are evaluated in the framework of density functional theory by a coupled perturbed Hartree-Fock method, support the experimental trend. The switching of optical nonlinearity has been achieved between the neutral and the one-electron oxidation products but not between the one- and the two-electron oxidation products since dications that are electrochemically reversible are unstable due to the formation of stable isoporphyrins in the presence of nucleophiles such as halides.