Synthesis of deuterium-enriched and fluorine-substituted plinabulin derivatives and evaluation of their antitumor activities

Deuterium-enriched and fluorine-substituted compounds have been widely applied in drug discovery due to their advantages in the studies of clinical pharmacokinetics and metabolic profiles. Herein we synthesized a library of deuterated and fluorine-substituted plinabulin derivatives, and all 15 D- or F-compounds were characterized by MS, \(^{1}\hbox {H}\) NMR and \(^{ 13}\hbox {C}\,\hbox {NMR}\). Their antitumor activities were evaluated against human Jurkat T lymphocyte cells.     

Combinatorial synthesis of deuterium-enriched (<Emphasis Type="Italic">S</Emphasis>)-oxybutynin

The concept of deuterium enrichment has gained more attention due to its advantages in the studies of clinical pharmacokinetics and metabolic profiles. In addition, it is cost and time efficient to develop deuterium-enriched drugs. Herein we built a combinatorial library of deuterated (S)-oxybutynins which all 8 D-compounds were characterized by MS, \(^{1}\hbox {H}\) NMR and \(^{ 13}\)C NMR.     

Conventional and microwave-assisted synthesis of new indole-tethered benzimidazole-based 1,2,3-triazoles and evaluation of their antimycobacterial,antioxidant and antimicrobial activities

A new series of triheterocycles containing indole–benzimidazole-based 1,2,3-triazole hybrids have been synthesized in good yields via a microwave-assisted click reaction. All the compounds were characterized by IR, \(^{1}\hbox {H}\) NMR, \(^{13}\hbox {C}\) NMR and mass spectroscopy and were evaluated for their in vitro antitubercular activity against the Mycobacterium tuberculosis H37Rv strain. Compounds 4b, 4h and 4i displayed highly potent antitubercular activity with MIC 3.125–6.25 \(\upmu \hbox {g}/\hbox {mL}\). The antioxidant potential was evaluated using 2,2-diphenyl-1-picryl hydrazine and \(\hbox {H}_{2}\hbox {O}_{2}\) radical scavenging activity, and compounds 4e,4f and 4g showed excellent radical scavenging activity with \(\hbox {IC}_{50}\) values in the range of 08.50–10.05 \(\upmu \hbox {g}/\hbox {mL}\). Furthermore, the compounds were evaluated for antimicrobial activity against numerous bacterial and fungal strains, and compounds 4b, 4c and 4h were found to be the most promising potential antimicrobial molecules with MIC 3.125–6.25 \(\upmu \hbox {g}/\hbox {mL}\).     

Design and one-pot synthesis of 2-thiazolylhydrazone derivatives as influenza neuraminidase inhibitors

Two series of novel 2-thiazolylhydrazone derivatives were designed and synthesized via one-pot reaction of benzaldehyde derivatives, \(\alpha \)-haloketones and thiosemicarbazide. The structures of compounds 1 and 2 were characterized by \(^{1}\hbox {H}\) NMR and \(^{13}\hbox {C}\) NMR, and compound 1g was further confirmed by X-ray crystallography. All of the target compounds were evaluated for their NA inhibitory activity against influenza viral neuraminidase (H1N1) in vitro, and the results showed that many compounds exhibited moderate to strong inhibitory activities against influenza viral neuraminidase (H1N1). Among them, compounds 1p, 1q and 2c showed the most potent inhibitory activities with \(\hbox {IC}_{50}\) values ranging from 10.50 to \(13.75\, \upmu \hbox {g}/\hbox {mL}\). Our structure–activity relationship analysis indicated that 2-thiazolylhydrazone is an effective scaffold for NA inhibitors and that introducing an ethoxycarbonyl group to the 5-position of thiazole ring could enhance inhibitory potency. Molecular docking was performed on the most active compounds 1p and 2c to provide more insight into their mechanism of interaction.     

Spin-label Order Parameter Calibrations for Slow Motion

Calibrations are given to extract orientation order parameters from pseudo-powder electron paramagnetic resonance line shapes of ¹⁴N-nitroxide spin labels undergoing slow rotational diffusion. The nitroxide z-axis is assumed parallel to the long molecular axis. Stochastic-Liouville simulations of slow-motion 9.4-GHz spectra for molecular ordering with a Maier–Saupe orientation potential reveal a linear dependence of the splittings, \(2A_{\hbox{max} }\) and \(2A_{\hbox{min} }\), of the outer and inner peaks on order parameter \(S_{zz}\) that depends on the diffusion coefficient \(D_{{{\text{R}} \bot }}\) which characterizes fluctuations of the long molecular axis. This results in empirical expressions for order parameter and isotropic hyperfine coupling: \(S_{zz} = s_{1} \times \left( {A_{\hbox{max} } - A_{\hbox{min} } } \right) - s_{o}\) and \(a_{o}^{{}} = \tfrac{1}{3}\left( {f_{\hbox{max} } A_{\hbox{max} } + f_{\hbox{min} } A_{\hbox{min} } } \right) + \delta a_{o}\), respectively. Values of the calibration constants \(s_{1}\), \(s_{\text{o}}\), \(f_{\hbox{max} }\), \(f_{\hbox{min} }\) and \(\delta a_{o}\) are given for different values of \(D_{{{\text{R}} \bot }}\) in fast and slow motional regimes. The calibrations are relatively insensitive to anisotropy of rotational diffusion \((D_{{{\text{R}}//}} \ge D_{{{\text{R}} \bot }} )\), and corrections are less significant for the isotropic hyperfine coupling than for the order parameter.     

Rapid communication: $$K_{S}^{0}$$ Production from beryllium target using 120 $$\hbox {GeV}/\hbox {c}$$GeV/c protons beam interactions at the MIPP experiment

We have measured the cross-section for the \(K_{S}^{0}\) production from beryllium target using 120 \(\hbox {GeV}/\hbox {c}\) protons beam interactions at the main injector particle production (MIPP) experiment at Fermilab. The data were collected with target having a thickness of 0.94% of the nuclear interaction length. The \(K_{S}^{0}\) inclusive differential cross-section in bins of momenta is presented covering momentum range from \(0.4\,\hbox {GeV}/\hbox {c}\) to \(30\,\hbox {GeV}/\hbox {c}\). The measured inclusive \(K_{S}^{0}\) production cross-section amounts to \(39.54\pm 1.46\delta _{\mathrm {stat}}\pm 6.97\delta _{\mathrm {syst}}\) mb and the value is compared with the prediction of FLUKA hadron production model.     

Fabrication and photoresponse of n-$$\hbox {WS}_{2}/$$p-V$$_{0.25}$$0.25W$$_{0.75}$$0.75Se$$_{2}$$2 van der Waals heterojunction

Excitation functions for \(\alpha \)-induced reactions on natural vanadium were measured in the energy range up to 20 MeV. The stacked-foil activation technique was used. The experimental results were compared with the theoretical calculations using EMPIRE-3.1, EMPIRE-3.2.2 and TENDL 2015, and with earlier experimental results. Thick target yields were calculated for the production of \(^{54}\hbox {Mn}\) and for the associated impurity \(^{52}\hbox {Mn}\).     

X-ray spectra and valence states of cations in nanostructured half-doped $$\hbox {La}_{0.5}\hbox {Ca}_{0.5}\hbox {MnO}_{3}$$ manganite

Soft X-ray absorption (XAS) and emission (XES) spectroscopies were applied to determine valence states of manganese ions in nanostructured powder of half-doped \(\hbox {La}_{0.5}\hbox {Ca}_{0.5}\hbox {MnO}_{3}\) manganite obtained by milling in a ball mill. XAS spectra were measured both in surface-sensitivity total electron-yield and in bulk-sensitivity total fluorescence-yield modes. O K\(_{\upalpha }\) XES and O 1s XAS spectra characterized the occupied and unoccupied partial O 2p densities of states are compared with band-structure calculations made using the TB-LMTO-ASA codes. Experimental Mn 2p, Ca 2p, and La 3\(d\) XAS spectra are compared with results of crystal field atomic multiplet calculations. For the nanostructured system of \(\hbox {La}_{0.5}\hbox {Ca}_{0.5}\hbox {MnO}_{3}\), concentrations of Mn\(^{4+}\) ions are found to be increased with increasing the time of milling.     

Search of the neutrino-less double beta decay of $$^{}$$Se into the excited states of $$^{}$$Kr with CUPID-0

The CUPID-0 experiment searches for double beta decay using cryogenic calorimeters with double (heat and light) read-out. The detector, consisting of 24 ZnSe crystals 95\(\%\) enriched in \(^{82}\)Se and two natural ZnSe crystals, started data-taking in 2017 at Laboratori Nazionali del Gran Sasso. We present the search for the neutrino-less double beta decay of \(^{82}\)Se into the 0\(_1^+\), 2\(_1^+\) and 2\(_2^+\) excited states of \(^{82}\)Kr with an exposure of 5.74 kg\(\cdot \)yr (2.24\(\times \)10\(^{25}\) emitters\(\cdot \)yr). We found no evidence of the decays and set the most stringent limits on the widths of these processes: \(\varGamma \)(\(^{82}\)Se \(\rightarrow ^{82}\)Kr\(_{0_1^+}\))8.55\(\times \)10\(^{-24}\) yr\(^{-1}\), \(\varGamma \) (\(^{82}\) Se \(\rightarrow ^{82}\) Kr \(_{2_1^+}\))\(\,{<}\,6.25 \,{\times }\,10^{-24}\) yr\(^{-1}\), \(\varGamma \)(\(^{82}\)Se \(\rightarrow ^{82}\)Kr\(_{2_2^+}\))8.25\(\times \)10\(^{-24}\) yr\(^{-1}\) (90\(\%\) credible interval).     

$$\varvec{B^0\rightarrow K^{*0}\mu ^+\mu ^-}$$ decay in the aligned two-Higgs-doublet model

In the aligned two-Higgs-doublet model, we perform a complete one-loop computation of the short-distance Wilson coefficients \(C_{7,9,10}^{(\prime )}\), which are the most relevant ones for \(b\rightarrow s\ell ^+\ell ^-\) transitions. It is found that, when the model parameter \(\left| \varsigma _{u}\right| \) is much smaller than \(\left| \varsigma _{d}\right| \), the charged scalar contributes mainly to chirality-flipped \(C_{9,10}^\prime \), with the corresponding effects being proportional to \(\left| \varsigma _{d}\right| ^2\). Numerically, the charged-scalar effects fit into two categories: (A) \(C_{7,9,10}^\mathrm {H^\pm }\) are sizable, but \(C_{9,10}^{\prime \mathrm {H^\pm }}\simeq 0\), corresponding to the (large \(\left| \varsigma _{u}\right| \), small \(\left| \varsigma _{d}\right| \)) region; (B) \(C_7^\mathrm {H^\pm }\) and \(C_{9,10}^{\prime \mathrm {H^\pm }}\) are sizable, but \(C_{9,10}^\mathrm {H^\pm }\simeq 0\), corresponding to the (small \(\left| \varsigma _{u}\right| \), large \(\left| \varsigma _{d}\right| \)) region. Taking into account phenomenological constraints from the inclusive radiative decay \(B\rightarrow X_{s}{\gamma }\), as well as the latest model-independent global analysis of \(b\rightarrow s\ell ^+\ell ^-\) data, we obtain the much restricted parameter space of the model. We then study the impact of the allowed model parameters on the angular observables \(P_2\) and \(P_5'\) of \(B^0\rightarrow K^{*0}\mu ^+\mu ^-\) decay, and we find that \(P_5'\) could be increased significantly to be consistent with the experimental data in case B.     

Structural and optical properties of BaZrO$$_{}$$:Eu$$^{+}$$+phosphor

BaZrO\(_{3}\):Eu\(^{3+}\) perovskite phosphors were successfully synthesized by employing combustion method. The structure, morphology and optical properties of material have been characterized by X-ray diffraction, scanning electron microscopy and fluorescence spectrometry. The XRD results indicate that crystals of BaZrO\(_{3}\):Eu\(^{3+}\) belongs to cubic perovskite system. The phosphors can be effectively excited by UV light and the emission spectra results indicate that reddish-orange luminescence dominates due to parity allowed magnetic dipole transition \(^{5}\)D\(_{0}\rightarrow ^{7}\)F\(_{1}\) located at 593 nm. The prepared phosphor show remarkable luminescent properties which find applications in field emission displays and plasma display panels.     

Exotic tetraquark states with the $$qq\bar{Q}\bar{Q}$$ configuration

In this work, we study systematically the mass splittings of the \(qq\bar{Q}\bar{Q}\) (\(q=u\), d, s and \(Q=c\), b) tetraquark states with the color-magnetic interaction by considering color mixing effects and estimate roughly their masses. We find that the color mixing effect is relatively important for the \(J^P=0^+\) states and possible stable tetraquarks exist in the \(nn\bar{Q}\bar{Q}\) (\(n=u\), d) and \(ns\bar{Q}\bar{Q}\) systems either with \(J=0\) or with \(J=1\). Possible decay patterns of the tetraquarks are briefly discussed.     

Applicability of strange nonchaotic Wien-bridge oscillators for secure communication

A numerical analysis of ion cyclotron resonance heating scenarios in two species of low ion temperature plasma has been done to elucidate the physics and possibility to achieve H-mode in tokamak plasma. The analysis is done in the steady-state superconducting tokamak, SST-1, using phase-I plasma parameters which is basically L-mode plasma parameters having low ion temperature and magnetic field with the help of the ion cyclotron heating code TORIC combined with ‘steady state Fokker–Planck quasilinear’ (SSFPQL) solver. As a minority species hydrogen has been used in \(^3\hbox {He}\) and \(^4\hbox {He}\) plasmas to make two species \(^3\hbox {He(H)}\) and \(^4\hbox {He(H)}\) plasmas to study the ion cyclotron wave absorption scenarios. The minority heating is predominant in \(^3\hbox {He(H)}\) and \(^4\hbox {He(H)}\) plasmas as minority resonance layers are not shielded by ion–ion resonance and cut-off layers in both cases, and it is better in \(^4\hbox {He(H)}\) plasma due to the smooth penetration of wave through plasma–vacuum surface. In minority concentration up to 15%, it has been observed that minority ion heating is the principal heating mechanism compared to electron heating and heating due to mode conversion phenomena. Numerical analysis with the help of SSFPQL solver shows that the tail of the distribution function of the minority ion is more energetic than that of the majority ion and therefore, more anisotropic. Due to good coupling of the wave and predominance of the minority heating regime, producing energetic ions in the tail region of the distribution function, the \(^4\hbox {He(H)}\) and \(^3\hbox {He(H)}\) plasmas could be studied in-depth to achieve H-mode in two species of low-temperature plasma.     

First-principle calculations of structural,electronic, optical,elastic and thermal properties of $$\hbox {MgXAs}_{2}$$ ($$\hbox {X}=\hbox {Si}, \hbox {Ge}$$X=Si,Ge) compounds

First-principle calculations on the structural, electronic, optical, elastic and thermal properties of the chalcopyrite \(\hbox {MgXAs}_{2}\) (\(\hbox {X}=\hbox {Si}, \hbox {Ge}\)) have been performed within the density functional theory (DFT) using the full-potential linearized augmented plane wave (FP-LAPW) method. The obtained equilibrium structural parameters are in good agreement with the available experimental data and theoretical results. The calculated band structures reveal a direct energy band gap for the interested compounds. The predicted band gaps using the modified Becke–Johnson (mBJ) exchange approximation are in fairly good agreement with the experimental data. The optical constants such as the dielectric function, refractive index, and the extinction coefficient are calculated and analysed. The independent elastic parameters namely, \(C_{11}\), \(C_{12}\), \(C_{13}\), \(C_{33}\), \(C_{44}\) and \(C_{66 }\) are evaluated. The effects of temperature and pressure on some macroscopic properties of \(\hbox {MgSiAs}_{2}\) and \(\hbox {MgGeAs}_{2}\) are predicted using the quasiharmonic Debye model in which the lattice vibrations are taken into account.     

Test the mergers of the primordial black holes by high frequency gravitational-wave detector

The black hole could have a primordial origin if its mass is less than \(1M_\odot \). The mergers of these black hole binaries generate stochastic gravitational-wave background (SGWB). We investigate the SGWB in high frequency band \(10^{8}\)–\(10^{10}\,\mathrm {Hz}\). It can be detected by high frequency gravitational-wave detector. Energy density spectrum and amplitude of the SGWB are derived. The upper limit of the energy density spectrum is around \(10^{-7}\). Also, the upper limit of the amplitude ranges from \(10^{-31.5}\) to \(10^{-29.5}\). The fluctuation of spacetime origin from gravitational wave could give a fluctuation of the background electromagnetic field in a high frequency gravitational-wave detector. The signal photon flux generated by the SGWB in the high frequency band \(10^{8}\)–\(10^{10}\,\mathrm {Hz}\) is derived, which ranges from 1 to \(10^2\,\mathrm {s^{-1}}\). The comparison between the signal photon flux generated by relic gravitational waves (RGWs) and the SGWB is also discussed in this paper. It is shown that the signal photon flux generated by the RGW, which is predicted by the canonical single-field slow-roll inflation models, is sufficiently lower than the one generated by the SGWB in the high frequency band \(10^{8}\)–\(10^{10}\,\mathrm {Hz}\). Our results indicate that the SGWB in the high frequency band \(10^{8}\)–\(10^{10}\,\mathrm {Hz}\) is more likely to be detected by the high frequency gravitational-wave detector.     

Decay widths of the spin-2 partners of the <Emphasis Type="Italic">X</Emphasis>(3872)

We consider the X(3872) resonance as a \(J^\mathrm{{PC}}=1^{++}\) \(D\bar{D}^*\) hadronic molecule. According to heavy quark spin symmetry, there will exist a partner with quantum numbers \(2^{++}\), \(X_{2}\), which would be a \(D^*\bar{D}^*\) loosely bound state. The \(X_{2}\) is expected to decay dominantly into \(D\bar{D}\), \(D\bar{D}^*\) and \(\bar{D} D^*\) in d-wave. In this work, we calculate the decay widths of the \(X_{2}\) resonance into the above channels, as well as those of its bottom partner, \(X_{b2}\), the mass of which comes from assuming heavy flavor symmetry for the contact terms. We find partial widths of the \(X_{2}\) and \(X_{b2}\) of the order of a few MeV. Finally, we also study the radiative \(X_2\rightarrow D\bar{D}^{*}\gamma \) and \(X_{b2} \rightarrow \bar{B} B^{*}\gamma \) decays. These decay modes are more sensitive to the long-distance structure of the resonances and to the \(D\bar{D}^{*}\) or \(B\bar{B}^{*}\) final state interaction.     

Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole-pyrrolidine derivatives and their biological applications

A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including \(^{1}\hbox {H}\), \(^{13}\hbox {C}\), 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a–r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f \((\hbox {IC}_{50} = 18.35~\upmu \hbox {M})\) showed significant cytotoxic activity compared to the standard drug doxorubicin \((\hbox {IC}_{50 }= 15.00~\upmu \hbox {M})\).     

Fully constrained Majorana neutrino mass matrices using $$\varvec{\varSigma (72\times 3)}$$

In 2002, two neutrino mixing ansatze having trimaximally mixed middle (\(\nu _2\)) columns, namely tri-chi-maximal mixing (\(\text {T}\chi \text {M}\)) and tri-phi-maximal mixing (\(\text {T}\phi \text {M}\)), were proposed. In 2012, it was shown that \(\text {T}\chi \text {M}\) with \(\chi =\pm \,\frac{\pi }{16}\) as well as \(\text {T}\phi \text {M}\) with \(\phi = \pm \,\frac{\pi }{16}\) leads to the solution, \(\sin ^2 \theta _{13} = \frac{2}{3} \sin ^2 \frac{\pi }{16}\), consistent with the latest measurements of the reactor mixing angle, \(\theta _{13}\). To obtain \(\text {T}\chi \text {M}_{(\chi =\pm \,\frac{\pi }{16})}\) and \(\text {T}\phi \text {M}_{(\phi =\pm \,\frac{\pi }{16})}\), the type I see-saw framework with fully constrained Majorana neutrino mass matrices was utilised. These mass matrices also resulted in the neutrino mass ratios, \(m_1:m_2:m_3=\frac{\left( 2+\sqrt{2}\right) }{1+\sqrt{2(2+\sqrt{2})}}:1:\frac{\left( 2+\sqrt{2}\right) }{-1+\sqrt{2(2+\sqrt{2})}}\). In this paper we construct a flavour model based on the discrete group \(\varSigma (72\times 3)\) and obtain the aforementioned results. A Majorana neutrino mass matrix (a symmetric \(3\times 3\) matrix with six complex degrees of freedom) is conveniently mapped into a flavon field transforming as the complex six-dimensional representation of \(\varSigma (72\times 3)\). Specific vacuum alignments of the flavons are used to arrive at the desired mass matrices.     

Republication of: Mean density of radiation in the Metagalaxy and certain problems in relativistic cosmology

This paper appeared in Russian in Doklady AN SSSR and in English in the translation journal Soviet Physics–Doklady. In it the cosmic radiation from galaxies in the frequency range \(10^8 \hbox {Hz}\) to \(10^{15} \hbox {Hz}\) was estimated and shown to agree with data. It was then shown, following earlier ideas of Gamow, that the black-body cosmic microwave background from a big bang would significantly exceed the galactic radiation in the range \(10^9 \hbox {Hz}\) to \(10^{11} \hbox {Hz}\). This was the first accurate prediction of that background, which now plays a key role in cosmology. The first announcement of its detection came in the following year. The paper has been selected by the Editors of General Relativity and Gravitation for re-publication in the Golden Oldies series of the journal. This republication is accompanied by an editorial note written by R. Durrer and a brief autobiography by A. G. Doroshkevich: an autobiography of I. D. Novikov appeared with a previous Golden Oldie.