Characteristic ion clusters as determinants for the identification of pyrrolizidine alkaloid N-oxides in pyrrolizidine alkaloid-containing natural products using HPLC-MS analysis

Pyrrolizidine alkaloid (PA)-containing plants are widely distributed in the world. PAs are hepatotoxic, affecting livestock and humans. PA N-oxides are often present together with PAs in plants and also exhibit hepatotoxicity but with less potency. HPLC-MS is generally used to analyze PA-containing herbs, although PA references are unavailable in most cases. However, to date, without reference standards, HPLC-MS methodology cannot distinguish PA N-oxides from PAs because they both produce the same characteristic ions in mass spectra. In the present study, the mass spectra of 10 PA N-oxides and the corresponding PAs were systemically investigated using HPLC-MS to define the characteristic mass fragment ions specific to PAs and PA N-oxides. Mass spectra of toxic retronecine-type PA N-oxides exhibited two characteristic ion clusters at m/z 118-120 and 136-138. These ion clusters were produced by three unique fragmentation pathways of PA N-oxides and were not found in their corresponding PAs. Similarly, the nontoxic platynecine-type PA N-oxides also fragmented via three similar pathways to form two characteristic ion clusters at m/z 120-122 and 138-140. Further application of using these characteristic ion clusters allowed successful and rapid identification of PAs and PA N-oxides in two PA-containing herbal plants. Our results demonstrated, for the first time, that these characteristic ion clusters are unique determinants to discriminate PA N-oxides from PAs even without the availability of reference samples. Our findings provide a novel and specific method to differentiate PA N-oxides from PAs in PA-containing natural products, which is crucial for the assessment of their intoxication.     

An efficient three-component, one-pot synthesis of 2-alkylthio-4-amino-5-cyano-6-aryl(alkyl)pyrimidines in water

A convenient and practical method for the synthesis of 2-alkylthio-4-amino-5-cyano-6-aryl(alkyl)pyrimidines has been developed via a three-component, one-pot reaction from aldehydes, malononitrile and S-alkylisothiouronium salts in water at room temperature. A series of polysubstituted pyrimidines were prepared by this method in moderate to excellent yields. In addition, two kinds of pyrimidine-fused heterocyclic derivatives with potential pharmacological activity were constructed from our 2-alkylthio-4-amino-5-cyano-6-arylpyrimidines.     

Residual symmetries for neutrino mixing with a large θ13 and nearly maximal δD

The residual Z(2)(s)(k) and Z(2)(s)(k) symmetries induce a direct and unique phenomenological relation with θx (≡ θ13) expressed in terms of the other two mixing angles θs(≡ θ12) and θa(≡ θ23) and the Dirac CP phase δD. Z(2)(s)(k) predicts a θx probability distribution centered around 3°-6° with an uncertainty of 2°-4°, while those from Z(2)(s)(k) are approximately a factor of 2 larger. Either result fits the T2K, MINOS, and Double Chooz measurements. Alternately, a prediction for the Dirac CP phase δD results in a peak at ± 74° (± 106°) for Z(2)(s)(k) or ± 123° (± 57°) for Z(2)(s)(k) which is consistent with the latest global fit. We also give a distribution for the leptonic Jarlskog invariant Jν which can provide further tests from measurements at T2K and NOνA.     

The study on neural contrast sensitivity function at temporal frequencies

The neural contrast sensitivity function (NCSF) of human eye at temporal frequencies is acquired with a new method in this paper. Firstly the human eye's contrast sensitivity function (CSF) at temporal frequencies is measured by means of travelling-wave stimuli, and the modulation transfer function (MTF) of the eye's optics is obtained by constructing the eye model of the subject. Then the NCSF at temporal frequencies is calculated with the two functions. It is shown that the overall value of the NCSF decreases as the temporal frequency increases. As the temporal frequency increases from 0 cycles per second (c/s) to 1 c/s, 16 c/s and 30 c/s, the NCSF curve changes from the band-pass shape to the low-pass, and then to almost monotonic variation. The attenuation factor of the NCSF, which represents the sensitivity of visual neural system to the temporal frequency, varies little as spatial frequency increases, while that of the CSF declines dramatically in the region of high spatial frequencies. Because it is the NCSF, rather than the CSF, that reflects the characteristics of visual neural system, the investigation of the NCSF at temporal frequency is more essentially.     

Ugi reaction-assisted rapid assembly of affinity-based probes against potential protein tyrosine phosphatases

The multi-component Ugi reaction has been employed to assemble a small library of affinity-based probes (AfBPs) that target potential protein tyrosine phosphatases. The probes showed good labelling of PTP1B and MptpB, and were subsequently used to label endogenous PTP1B in MCF-7 cell lysates.     

Unique biocatalytic resolution of racemic tetrahydroberberrubine via kinetic glycosylation and enantio-selective sulfation

In this communication, we document a facile kinetic glycosylation resolution of racemic tetrahydroberberrubine. We also demonstrate that the enantiomeric excess of the resolved products is increased via a second resolution of the minor product of the first glycosylation resolution. This provides a rare example of tandem kinetic resolution of racemates.     

Light-triggered reversible assemblies of azobenzene-containing amphiphilic copolymer with β-cyclodextrin-modified hollow mesoporous silica nanoparticles for controlled drug release

Hollow mesoporous silica nanoparticles (HMSs) were modified by β-cyclodextrin via a "click" reaction, an amphiphilic copolymer with a trans-azobenzene structure was then assembled onto β-cyclodextrin to cover the surface of the HMSs. The prepared nanocomposites can release drugs in a "release-stop-release" manner by converting light irradiation.     

Enantioselective synthesis of substituted pyrans via amine-catalyzed Michael addition and subsequent enolization/cyclisation

An organocatalytic construction of optically enriched substituted pyran derivatives via amine-catalyzed Michael addition and subsequent enolization/cyclisation has been described starting from electronically poor alkenes. Functionalized pyrans were obtained in high enantioselectivities (up to 96%) and good yields (up to 90%) having three contiguous chiral centers.     

Chiral pyrrolidine quaternary derivatives as organocatalysts for asymmetric Michael additions

A series of chiral pyrrolidine quaternary derivatives were designed and synthesized. It was found that these derivatives are highly efficient organocatalysts for the asymmetric Michael addition reactions of aldehydes and ketones to nitroolefins with high yields (up to 96%), high enantioselectivities (up to 99% ee), and high diastereoselectivities (up to 97:3 dr). Furthermore, catalyst 7a could be recycled without remarkable loss of catalytic activity and stereoselectivity.