α-Glucosidase inhibitors from Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit: molecular docking and interaction mechanism of flavonols with different B-ring hydroxylations

Inhibition of α-glucosidase alleviates postprandial high glycemic levels in diabetic or prediabetic population. In Chinese bayberry fruit, myricetin, quercetin and kaempferol are main flavonols, which differ only in their hydroxylation on the B-ring. Kaempferol (4′-OH) showed high IC₅₀ (65.36 ± 0.27 μmol L⁻¹) against α-glucosidase, while quercetin (3′,4′-OH) exhibited stronger inhibition (46.91 ± 0.54 μmol L⁻¹) and myricetin (3′,4′,5′-OH) possessed the strongest inhibitory activity (33.20 ± 0.43 μmol L⁻¹). Molecular docking analysis illustrated that these flavonols could insert to the active cavity of α-glucosidase. Adjacent hydroxyl groups at B-ring of myricetin and quercetin positively contributed to form hydrogen bonds that were important to the stability of flavonol–enzyme complex, while kaempferol had no adjacent hydroxyl groups. Such observation was further validated by molecular dynamics simulations, and in good consistency with in vitro kinetic analysis and fluorescence spectroscopy analysis. Among three flavonols tested, myricetin possessed the strongest inhibition effects on α-glucosidase with the lowest dissociation constant (K_i = 15.56 μmol L⁻¹) of myricetin-α-glucosidase, largest fluorescence quenching constant (K_sv) of (14.26 ± 0.03) × 10⁴ L mol⁻¹ and highest binding constant (K_a) of (1.38 ± 0.03) × 10⁵ L mol⁻¹ at 298 K with the enzyme. Bio-Layer Interferometry (BLI) and circular dichroism (CD) analysis further confirmed that myricetin had high affinity to α-glucosidase and induced conformational changes of enzyme. Therefore, myricetin, quercetin and kaempferol are all excellent dietary α-glucosidase inhibitors and their inhibitory activities are enhanced by increasing number of hydroxyl groups on B-ring.

Inhibition of α-glucosidase alleviates postprandial high glycemic levels in diabetic or prediabetic population.     

Correction: Nanoarchitectonics of p-type BiSbTe with improved figure of merit via introducing PbTe nanoparticles

Correction for ‘Nanoarchitectonics of p-type BiSbTe with improved figure of merit via introducing PbTe nanoparticles’ by Yuanyue Li et al., RSC Adv., 2021, 11, 36636–36643, DOI: 10.1039/D1RA07138F.

The authors regret that affiliation a was incorrectly given in the original article. The correct affiliation is shown here.In the sentence beginning “For instance, PF of the sample with χ = 0.5 wt% is 33.8…” incorrect units were given. The corrected sentence is as follows: For instance, PF of the sample with χ = 0.5 wt% is 33.8 μW cm⁻¹ K⁻² at 482 K, which is ∼33% larger than that of the BST matrix (25.5 μW cm⁻¹ K⁻²).In the sentence beginning “For instance, as to the sample with χ = 0.5 wt%, κ decreases from 1.10…” incorrect units were given. The corrected sentence is as follows: For instance, as to the sample with χ = 0.5 wt%, κ decreases from 1.10 to 0.99 W m⁻¹ K⁻¹ at 482 K (a ∼10% decline).The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Thermally controlled biotransformation of glycyrrhizic acid via an asymmetric temperature-responsive polyurethane membrane

Separating a target product from a relatively complex bioreaction system is often difficult. In this work, a “smart” bioreaction system was developed by using the special characteristic of temperature-responsive polyurethane (TRPU). By combining solvent evaporation with a wet phase inversion technique, an asymmetric membrane consisting of an integral and dense skin layer supported by a porous sublayer was prepared from a thermally responsive polyurethane that experiences a sudden free volume increase upon heating through a phase transition temperature of 56 °C. Subsequently, the asymmetric TRPU membrane served as the carrier of an immobilized enzyme, wherein β-glucuronidase was multipoint-conjugated by using biotin and streptavidin on the porous sublayer. Then, the material-asymmetric TRPU membrane served jointly as the antennae as well as the actuator, which reversibly responds to temperature to switch (on–off) the access of the reactant glycyrrhizic acid (GL). Under the optimal temperature (40 °C) and pH (7.0) conditions, the immobilized β-glucuronidase contributed to almost 33% yield of glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG) of the isolated counterpart for the same concentration of substrate (250 mg L⁻¹) reaction for 24 h, while costing 1% of that of the isolated β-glucuronidase. Kinetic results showed that V_max and K_m values were 8.89 × 10³ mg L⁻¹ and 2.30 × 10³ mg L⁻¹ h⁻¹, respectively. The specific functional polymer-immobilized β-glucuronidase design serves as a bioreactor of GL into GAMG, as well as a separator deliberately irritated and controlled by temperature. This “smart” support material presents a potential facilitator for the separation of complex biotransformation reactions.

A “smart” bioreaction system was developed by using the special characteristic of a temperature-responsive polyurethane (TRPU). This “smart” support material presents a potential benefit of separation for complex biotransformation reactions.     

Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus

To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tla^a-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tla^a-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg.Tla^a-3-1, Tg.Tla^a-3-2, and control C3H mice by skin grafts from H-2K^b/T3^b transgenic mice, Tg.Con.3-1, expressing T3^b-TL ubiquitously. Spleen cells from mice that had rejected the T3^b-TL positive skin grafts were restimulated in vitro with Tg.Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1⁺ T cells derived from Tg.Tla^a-3-1 and Tg.Tla^a-3-2, respectively, expressed TCRγδ, whereas almost all those from C3H expressed TCRαβ. The MLC from Tg.Tla^a-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg.Tla^a-3-1 had little or none. The generation of γδ CTL recognizing TL in Tg.Tla^a-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 γδ CTL clones were established from Tg.Tla^a-3-2, whereas none were obtained from C3H. Of the 14 γδ CTL clones, 8 were CD8⁺ and 6 were CD4⁻CD8⁻ double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCRγδ and CD3, and also by antibodies to CD8α and CD8β in CD8⁺ clones, showing that the activity was mediated by TCRγδ and coreceptors. The thymic origin of these γδ CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8αβ heterodimers in CD8⁺ clones on their surfaces and by the usage of TCR Vγ4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla^a-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of γδ T cells.     

Islet-Specific T-Cell Responses and Proinflammatory Monocytes Define Subtypes of Autoantibody-Negative Ketosis-Prone Diabetes

OBJECTIVE

Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative (“A−”) phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional reserve) and “A−β+” (obese, late onset, with substantial β-cell functional reserve after the index episode of DKA). Recent longitudinal analysis of a large KPD cohort revealed that the A−β+ phenotype includes two distinct subtypes distinguished by the index DKA episode having a defined precipitant (“provoked,” with progressive β-cell function loss over time) or no precipitant (“unprovoked,” with sustained β-cell functional reserve). These three A− KPD subtypes are characterized by absence of humoral islet autoimmune markers, but a role for cellular islet autoimmunity is unknown.

RESEARCH DESIGN AND METHODS

Islet-specific T-cell responses and the percentage of proinflammatory (CD14+CD16+) blood monocytes were measured in A−β− (n = 7), provoked A−β+ (n = 15), and unprovoked A−β+ (n = 13) KPD patients. Genotyping was performed for type 1 diabetes–associated HLA class II alleles.

RESULTS

Provoked A−β+ and A−β− KPD patients manifested stronger islet-specific T-cell responses (P < 0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P < 0.01) than unprovoked A−β+ KPD patients. A significant relationship between type 1 diabetes HLA class II protective alleles and negative T-cell responses was observed.

CONCLUSIONS

Provoked A−β+ KPD and A−β− KPD are associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations. In contrast, unprovoked A−β+ KPD lacks both humoral and cellular islet autoimmunity.Ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA) in patients lacking the typical features of autoimmune type 1 diabetes, is a heterogeneous syndrome (1,2). A validated classification scheme for KPD, based on the presence or absence of β-cell autoantibodies (“A+” or “A−”) and presence or absence of β-cell functional reserve (“β+” or “β−”) (3) includes two autoantibody-negative A− phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional reserve) and “A−β+” (obese, late onset, with substantial β-cell functional reserve after the index episode of DKA). Long-term longitudinal follow-up of a large cohort of A−β+ KPD patients has revealed that this phenotype comprises two distinct subtypes distinguished by whether the index DKA episode had a defined precipitant (“provoked” A−β+) or no precipitant (“unprovoked” A−β+) (4). Provoked A−β+ KPD patients have progressive loss of β-cell function after initial recovery from the DKA episode, with relapse to insulin dependence, no sex predominance, and an increased frequency of the HLA class II alleles DQB1*0302 and DRB1*04 associated with susceptibility to autoimmune type 1 diabetes. In contrast, unprovoked A−β+ KPD patients have sustained preservation of β-cell function after recovery from the DKA episode, prolonged insulin independence, male predominance, and an increased frequency of the protective allele DQB1*0602 (4). The unique clinical features and natural histories of these two subtypes of A−β+ KPD patients suggest distinctive underlying pathophysiologic processes for each. Although an underlying “occult” autoimmune element is suggested in the provoked A−β+ subtype by progressive β-cell loss and the presence of type 1 diabetes–associated HLA susceptibility alleles, the unprovoked A−β+ subtype could represent a truly nonautoimmune syndrome of KPD.We have previously shown that the T cells of a significant proportion of individuals with an apparent phenotype of type 2 diabetes react strongly to islet antigens, despite lacking β-cell autoantibodies, and that this reactivity is associated with low C-peptide levels, indicating underlying cellular immune damage to β-cells (5,6). This finding expands the range of diabetic phenotypes—including those labeled as having “type 2” diabetes—with a potential pathophysiologic basis in islet autoimmunity. In the current study, we extended these findings to the unique, emerging forms of A− KPD. Specifically, we hypothesized that differences in cellular immune responses might distinguish the three A− KPD subtypes (A−β−, unprovoked A−β+, and provoked A−β+) with regard to a cellular autoimmune etiology. To test this hypothesis, we measured islet-specific T-cell responses using the validated cellular immunoblotting assay and islet autoantibody responses to determine the presence of islet autoimmunity in patients carefully phenotyped for these three KPD subtypes. We further assessed the percentage of proinflammatory (CD14+CD16+) monocytes in the peripheral blood of the three KPD subtypes.In healthy subjects, 90–95% of classical monocytes express high levels of the cell surface marker CD14 (CD14+), without expression of CD16 (CD16−). Inflammation and infection are associated with the emergence of a distinct monocyte population characterized by coexpression of CD14 and CD16 (CD14+CD16+). CD14+CD16+ monocytes secrete high levels of proinflammatory tumor necrosis factor-α and low levels of anti-inflammatory interleukin-10, leading to their designation as proinflammatory monocytes (7).Our results demonstrate that 1) provoked A−β+ KPD, associated with progressive loss of β-cell function, is associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations; 2) unprovoked A− KPD is a distinct syndrome of reversible β-cell dysfunction lacking evidence of humoral or cellular islet autoimmunity; and 3) a substantial proportion of A−β− KPD patients, who resemble patients with type 1 diabetes but lack autoantibodies, have evidence of cellular islet autoimmunity.     

Optical properties of 3-substituted indoles

The optical properties of various donor or acceptor p-phenyl substituted ethenyl indoles were studied in solvents of varying polarity using absorption, fluorescence and TDDFT methods. Ethenyl indole exhibits non-linear optical properties (NLO) in a substituent dependent manner. Compound with a strong electron-attracting substituent, shows large NLO properties with charge transfer behavior, whereas ethenyls with moderate electron withdrawing or electron donating substituent exhibit lower NLO properties with non polar excited state. A highly dipolar excited state for p-nitro phenyl substituted ethenyl indoles (μ_e: 18.2–27.1 debye; Δμ: 9.4–17.8 debye) is observed as compared to other ethenyls (μ_e: 6.6–9.5 debye; Δμ: 4.2–6.2 debye). From TDDFT study, it is shown that the HOMO–LUMO energy of ethenyl is increased with increasing the electron donating ability of the p-phenyl substitution. The optical band gap of ethenyl 3 without substitution, is decreased upon p-phenyl substitution either with an electron withdrawing (Cl, NO₂) or an electron donating (OCH₃, OH, NH₂) substituent. The compound with a strong electron accepting, p-nitrophenyl ethenyl indole 1 shows 12 times better NLO response as compared to the reference ethenyl indole 3 (β: 1: 115 × 10⁻³⁰ esu⁻¹ cm⁵, 3: 9 × 10⁻³⁰ esu⁻¹ cm⁵). Ethenyls 2–6 bearing a weak or moderately electron withdrawing or electron accepting substituent, exhibit lower NLO response. The β of ethenyl is increased with increasing the order of electron withdrawing nature of phenyl ring. Overall, a correlation of β with the optical band gap, ground state dipole moment, % of charge transfer in the ground and excited state is found.

Various donor and acceptor p-phenyl substituted ethenyl indoles were synthesized and studied their optical properties in solvents of varying polarity using absorption, fluorescence and TDDFT methods.     

A porous β-cyclodextrin-based terpolymer fluorescence sensor for in situ trinitrophenol detection

Permanent porosity plays a key role in fluorescent-based polymers with “on–off” emissive properties due to the role of guest adsorption at accessible fluorophore sites of the polymer framework. In particular, we report on the design of a porous fluorescent polymer (FL-PFP) composed of a covalently cross-linked ternary combination of β-cyclodextrin (β-CD), 4,4′-diisocyanato-3,3′-dimethyl biphenyl (DL) and tetrakis(4-hydoxyphenyl)ethene (TPE). The textural properties of FL-PFP were evaluated by the gas uptake properties using N₂ and CO₂ isotherms. The BET surface area estimates according to N₂ uptake ranged from 100–150 m² g⁻¹, while a lower range of values (20–30 m² g⁻¹) was estimated for CO₂ uptake. Model nitroarenes such as trinitrophenol (TNP) and nitrobenzene (NB) were shown to induce turn-off of the fluorescence emission of the polymer framework at concentrations near 50 nM with ca. 50% fluorescence quenching upon TNP adsorption and detection. The strong donor–acceptor interaction between the nitroarenes and the TPE reporter unit led to fluorescence quenching of FL-PFP upon nitroarene adsorption. The fluorescence lifetime (τ) for FL-PFP (τ = 3.82 ns) was obtained along with a quantum yield estimate of 0.399 relative to quinine sulphate. The β-CD terpolymer reported herein has significant potential for monitoring the rapid and controlled detection of nitroarenes (TNP and NB) in aquatic environments and other complex media.

Permanent porosity plays a key role in fluorescent-based polymers with “on–off” emissive properties due to the role of guest adsorption at accessible fluorophore sites of the polymer framework.     

Efficient full-colour organic light-emitting diodes based on donor–acceptor electroluminescent materials with a reduced singlet–triplet splitting energy gap

A series of efficient blue-emitting materials, namely, Cz-DPVI, Cz-DMPVI, Cz-DEPVI and TPA-DEPVI, possessing a donor–acceptor architecture with dual carrier transport properties and small singlet–triplet splitting is reported. These compounds exhibit excellent thermal properties with a very high glass-transition temperature (T_g), and thus, a stable uniform thin film was formed during device fabrication. Among the weak donor compounds, specifically, Cz-DPVI, Cz-DMPVI and Cz-DEPVI, the Cz-DEPVI-based device showed the maximum efficiencies (L: 13 955 cd m⁻², η_ex: 4.90%, η_c: 6.0 cd A⁻¹, and η_p: 5.4 lm W⁻¹) with CIE coordinates of (0.15, 0.06) at 2.8 V. The electroluminescent efficiencies of Cz-DEPVI were higher than that of the strong donor TPA-DEPVI-based device (L: 13 856 cd m⁻², η_ex: 4.70%, η_c: 5.7 cd A⁻¹, and η_p: 5.2 lm W⁻¹). Furthermore, these blue emissive materials were used as hosts to construct efficient green and red phosphorescent OLEDs. The green device based on Cz-DEPVI:Ir(ppy)₃ exhibited the maximum L of 8891 cd m⁻², η_ex of 19.3%, η_c of 27.9 cd A⁻¹ and η_p of 33.4 lm W⁻¹ with CIE coordinates of (0.31, 0.60) and the red device based on Cz-DEPVI:Ir(MQ)₂(acac) exhibited the maximum L of 40 565 cd m⁻², η_ex of 19.9%, η_c of 26.0 cd A⁻¹ and η_p of 27.0 lm W⁻¹ with CIE coordinates of (0.64, 0.37).

The Cz-DEPVI device showed high efficiencies of L: 13955 cd m⁻², η_ex: 4.90%, η_c: 6.0 cd A⁻¹, η_p: 5.4 lm W⁻¹ and CIE coordinates of (0.15, 0.06) at 2.8 V.     

Synthesis,crystal structures and magnetic properties of two heterometallic {Ln8Cr4} (Ln = Gd3+ and Tb3+) complexes with one-dimensional wave chain structure

Two isomorphic heterometallic 3d–4f cluster-based materials, formulated [Gd₈Cr₄(IN)₁₈(μ₃-O)₂(μ₃-OH)₆(μ₄-O)₄(H₂O)₁₀]·13H₂O (1) and [Tb₈Cr₄(IN)₁₈(μ₃-O)₂(μ₃-OH)₆(μ₄-O)₄(H₂O)₁₀]·13H₂O (2) (abbreviation: {Ln₈Cr₄}: Ln = Gd³⁺ (1); Tb³⁺ (2); HIN = isonicotinic acid), were achieved by hydro-/solvothermal method through using the ligand HIN. X-ray diffraction analysis illustrates eight lanthanide ions (Ln = Gd³⁺, Tb³⁺) and four transition-metal ions (Cr³⁺) of {Ln₈Cr₄} were constructed from two classical “drum-like” {Ln₄Cr₂} structures associated by organic ligands HIN, displaying a one-dimensional wave chain structure, which is rare. The magnetic properties of {Gd₈Cr₄} were inspected and showed the existence of antiferromagnetic coupling interactions between contiguous metal ions. On top of this, the magnetic entropy change of ΔS_m can attain 23.40 J kg⁻¹ K⁻¹ (44.90 mJ cm⁻³ K⁻¹) at about 3 K and ΔH = 7 T. Besides, fluorescence measurements of {Tb₈Cr₄} display typical characteristic Tb-based luminescence.

Two heterometallic cluster {Ln₈Cr₄} were constructed from two classical “drum-like” {Ln₄Cr₂} building units associated by organic ligands HIN, displaying 1D wave chain structure. The MCE values for {Gd₈Cr₄} at 3 K and 7 T is 23.40 J kg⁻¹ K⁻¹.     

Efficient fluorescent OLEDS based on assistant acceptor modulated HLCT emissive state for enhancing singlet exciton utilization

Phenylamine phenanthroimidazole based bipolar compounds with donor–acceptor (D–A) architecture namely, 4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6,9-di(pyren-4-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)-N,N-diphenylaniline (DDPPPA) and 4′-(1-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6,9-di(pyren-4-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)-N,N-diphenyl-[1,1′-biphenyl]-4-amine (DDPBA) have been synthesized with highly fluorescent pyrene moieties at C6- and C9-positions. The C6 and C9 modification enhanced the thermal, photochemical and electroluminescent properties. Both molecules were employed as blue emitters in non doped organic light emitting devices (OLEDs) and show high performances due to hybridized local and charge-transfer properties. An OLED with DDPPPA/DDPBA emissive layer shows deep-blue emission with maximum external quantum efficiency (η_ex), current efficiency (η_c) and power efficiency (η_p) of 5.7/6.0%, 10.5/12.0 cd A⁻¹ and 8.3/9.2 lm W⁻¹, respectively. Both devices show high singlet exciton utilizing efficiency (η_s) of DDPPPA-31.33% and DDPBA-35.29%. The doped device m-MTDATA:DDPPPA/m-MTDATA:DDPBA shows maximum efficiencies of η_c −7.4/8.23 cd A⁻¹; η_p −5.8/6.13 lm W⁻¹; η_ex −4.72/5.63% (5 wt%):η_c −8.36/9.15 cd A⁻¹; η_p −6.32/6.65 lm W⁻¹; η_ex −4.86/5.45% (10 wt%):η_c −9.58/10.02 cd A⁻¹; η_p −7.8/8.25 lm W⁻¹; η_ex −5.96/6.25% (20 wt%). The doped device based on TAPC host TAPC:DDPPPA/TAPC:DDPBA exhibits maximum efficiencies of η_c −9.60/10.03 cd A⁻¹; η_p −7.81/8.26 lm W⁻¹; η_ex −5.96/6.25% (20 wt%).

OLED with C6/C9 substituted phenanthroimidazoles (DDPPPA/DDPBA) show blue emission with maximum external quantum efficiency (η_ex), current efficiency (η_c) and power efficiency (η_p) of 5.7/6.0%, 10.5/12.0 cd A⁻¹ and 8.3/9.2 lm W⁻¹, respectively.     

Strategic tuning of excited-state properties of electroluminescent materials with enhanced hot exciton mixing

Deep blue emitters with excellent stability, high quantum yield and multifunctionality are the major issues for full-color displays. In line with this, new multifunctional, thermally stable blue emitters viz., N-(4-(10-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)anthracen-9-yl)phenyl)-N-phenylbenzenamine (DPIAPPB) and 2-(10-(9H-carbazol-9-yl)anthracen-9-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-phenanthro[9,10-d]imidazole (CADPPI) with hybridized local charge transfer state (HLCT) and hot exciton properties have been synthesized. These molecules show high photoluminescence quantum yield (Φ_s/f): (DPIAPPB – 0.82/0.70 and CADPPI – 0.91/0.83). The CADPPI based device (EL – 467 nm) shows high efficiencies [η_c – 9.85 cd A⁻¹; η_p – 10.84 lm W⁻¹; η_ex – 4.78% at 2.8 V; CIE (0.15, 0.10)] compared to the DPIAPPB device (EL − 472 nm) [η_c – 6.56 cd A⁻¹; η_p – 6.16 lm W⁻¹; η_ex – 4.15% at 2.8 V with CIE (0.15, 0.12)]. The green device with CADPPI:Ir(ppy)₃ exhibits a maximum L – 59 012 cd m⁻²; η_ex – 16.8%; η_c – 37.3 cd A⁻¹; η_p – 39.8 lm W⁻¹ with CIE (0.30, 0.60) and the red device with CADPPI:Ir(MDQ)₂(acac) shows a maximum L – 43 456 cd m⁻²; η_ex – 21.9%; η_c – 36.0 cd A⁻¹; η_p – 39.6 lm W⁻¹ with CIE (0.64, 0.35).

The CADPPI:Ir(ppy)₃ device exhibits L – 90 12 cd m⁻²; η_ex – 18.8%; η_c − 27.3 cd A⁻¹; η_p – 29.8 lm W⁻¹; CIE (0.30, 0.60).     

Deciphering the selectivity of inhibitor MKC9989 towards residue K907 in IRE1α; a multiscale in silico approach

The selectivity of the ligand MKC9989, as inhibitor of the Inositol-Requiring Enzyme 1α (IRE1α) transmembrane kinase/ribonuclease protein, towards the residue K907 in the context of Schiff base formation, has been investigated by employing an array of in silico techniques including Multi-Conformation Continuum Electrostatics (MCCE) simulations, Quantum Mechanics/Molecular Mechanics (QM/MM) calculations, covalent docking, and Molecular Dynamics (MD) simulations. According to the MCCE results, K907 displays the lowest pK_a value among all 23 lysine residues in IRE1α. The MMCE simulations also indicate a critical interaction between K907 and D885 within the hydrophobic pocket which increases significantly at low protein dielectric constants. The QM/MM calculations reveal a spontaneous proton transfer from K907 to D885, consistent with the low pK_a value of K907. A Potential Energy Surface (PES) scan confirms the lack of energy barrier and transition state associated with this proton transfer reaction. Covalent docking and MD simulations verify that the protein pocket containing K907 can effectively stabilize the inhibitor by strong π–π and hydrogen bonding interactions. In addition, Radial Distribution Function (RDF) analysis shows that the imine group formed in the chemical reaction between MKC9989 and K907 is inaccessible to water molecules and thus the probability of imine hydrolysis is almost zero. The results of the current study explain the high selectivity of the MKC9989 inhibitor towards the K907 residue of IRE1α.

The high selectivity of inhibitor MKC9989 towards Lys907 of IRE1α is explained by the unique pK_a properties of the lysine.     

Experimental and DFT studies of sulfadiazine ‘piano-stool’ Ru(ii) and Rh(iii) complexes

While sulfadiazine (HL^SZ) is extensively used to elaborate complexes of intriguing biological applications (e.g. topical antibiotic silvadene; silver sulfadiazine), the molecular structure modification of sulfadiazine or even other sulfa drugs by coordination to either η⁶-cymene Ru(ii) or η⁵-Cp* Rh(iii) motif has not been investigated. Here, half-sandwich organoruthenium(ii) and organorhodium(iii) compounds of the type [(η⁶-p-cymene)Ru(L^SZ)₂] (1) and [(η⁵-C₅Me₅)Rh(L^SZ)₂] (2) are synthesized, characterized and evaluated for their potential antimicrobial activity. Spectroscopic and single crystal X-ray analysis showed that L^SZ is coordinated to Rh(iii) via both the sulfonamide and pyrimidine nitrogen atoms forming “piano-stool” geometry. In 2, the NMR equivalence clearly pointed to participation of two L^SZ molecules in a fluxional process in which the third bond of the base of the stool is oscillating between two equivalent sulfonamide nitrogen atoms. While 1 was biologically inactive, complex 2 was potent against Gram-positive bacteria, Candida albicans and Cryptococcus neoformans. Hen white egg lysozyme (HEWL), a model protein, reacted covalently with 2via the loss of one L^SZ molecule, while compound 1 decomposed during the interaction with that protein.

Binding of certain metal complexes to proteins may cause cytotoxicity. While [(η⁶-p-Cym)Ru(L^SZ)₂] decomposed during the reaction with hen white egg lysozyme, a Rh(iii) analogue was covalently bio-conjugated via the elimination of a sulfadiazine.     

Self-radiolysis of tritiated water. 4. The scavenging effect of azide ions (N3−) on the molecular hydrogen yield in the radiolysis of water by 60Co γ-rays and tritium β-particles at room temperature

The effect of the azide ion N₃⁻ on the yield of molecular hydrogen in water irradiated with ⁶⁰Co γ-rays (∼1 MeV Compton electrons) and tritium β-electrons (mean electron energy of ∼7.8 keV) at 25 °C is investigated using Monte Carlo track chemistry simulations in conjunction with available experimental data. N₃⁻ is shown to interfere with the formation of H₂ through its high reactivity towards hydrogen atoms and, but to a lesser extent, hydrated electrons, the two major radiolytic precursors of the H₂ yield in the diffusing radiation tracks. Chemical changes are observed in the H₂ scavengeability depending on the particular type of radiation considered. These changes can readily be explained on the basis of differences in the initial spatial distribution of primary radiolytic species (i.e., the structure of the electron tracks). In the “short-track” geometry of the higher “linear energy transfer” (LET) tritium β-electrons (mean LET ∼5.9 eV nm⁻¹), radicals are formed locally in much higher initial concentration than in the isolated “spurs” of the energetic Compton electrons (LET ∼0.3 eV nm⁻¹) generated by the cobalt-60 γ-rays. As a result, the short-track geometry favors radical–radical reactions involving hydrated electrons and hydrogen atoms, leading to a clear increase in the yield of H₂ for tritium β-electrons compared to ⁶⁰Co γ-rays. These changes in the scavengeability of H₂ in passing from tritium β-radiolysis to γ-radiolysis are in good agreement with experimental data, lending strong support to the picture of tritium β-radiolysis mainly driven by the chemical action of short tracks of high local LET. At high N₃⁻ concentrations (>1 M), our H₂ yield results for ⁶⁰Co γ-radiolysis are also consistent with previous Monte Carlo simulations that suggested the necessity of including the capture of the precursors to the hydrated electrons (i.e., the short-lived “dry” electrons prior to hydration) by N₃⁻. These processes tend to reduce significantly the yields of H₂, as is observed experimentally. However, this dry electron scavenging at high azide concentrations is not seen in the higher-LET ³H β-radiolysis, leading us to conclude that the increased amount of intra-track chemistry intervening at early time under these conditions favors the recombination of these electrons with their parent water cations at the expense of their scavenging by N₃⁻.

The effect of the azide ion on the yield of molecular hydrogen in water irradiated with ⁶⁰Co γ-rays and tritium β-electrons at 25 °C is investigated using Monte Carlo track chemistry simulations.     

Efficient electroluminescent hybridized local and charge-transfer host materials with small singlet–triplet splitting to enhance exciton utilization efficiency: excited state transition configuration

A series of efficient electroluminescent materials with dual carrier transport properties shows enhanced singlet exciton utilization (η_s) due to small singlet–triplet splitting (ΔE_ST). The strong orbital-coupling transitions of N-(4-(1-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4,5-diphenyl-1H-imidazol-2-yl)naphthalen-4-yl)phenyl)-N-phenyl benzenamine (DDPB) exhibit deep blue emission at 435 nm (CIEy, 0.07) with an external quantum efficiency of 2.01%. The electroluminescent efficiencies of 2-(1-(9H-carbazol-9-yl)naphthalen-4-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-phenanthro[9,10-d]imidazole (CDDPI) (L – 3992 cd m⁻²; η_ex – 3.01%; η_c – 2.56 cd A⁻¹; η_p – 2.12 lm W⁻¹) are higher than those of the N-(4-(1-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-H-phenanthro[9,10-d]imidazole-2-yl)naphthalen-4-yl)phenyl)-N-phenylbenzenamine (DBDPA) based device (L – 3015 cd m⁻²; η_ex – 2.85%; η_c – 2.01 cd A⁻¹; η_p – 1.92 lm W⁻¹). The blue emissive materials CDDPI and DBDPA are used as a host to construct green and red phosphorescent OLEDs: the green device based on CDDPI:Ir(ppy)₃ exhibits higher efficiencies (L – 8812 cd m⁻²; η_ex – 19.0%; η_c – 27.5 cd A⁻¹; η_p – 33.0 lm W⁻¹) at 2.7 V and the red device based on CDDPI:Ir(MQ)₂(acac) exhibits a maximum luminance of 39 661 cd m⁻² with excellent EL efficiencies [η_ex – 19.2%; η_c – 27.9 cd A⁻¹; η_p – 29.2 lm W⁻¹; CIE (0.64, 0.34)] compared with those of the DBDPA:Ir(MQ)₂(acac) based device [L – 37 621 cd m⁻²; η_ex – 18.5%; η_c – 25.2 cd A⁻¹; η_p – 25.8 lm W⁻¹; CIE (0.64, 0.34)].

CDDPI:Ir(ppy)₃ exhibits higher efficiencies: L = 8812 cd m⁻²; η_ex = 19.0%; η_c = 27.5 cd A⁻¹; η_p = 33.0 lm W⁻¹ at 2.7 V.     

Hot exciton transition for organic light-emitting diodes: tailoring excited-state properties and electroluminescence performances of donor–spacer–acceptor molecules

The photophysical, electrochemical and electroluminescent properties of newly synthesized blue emitters with donor–π–acceptor geometry, namely, 4′-(1-(naphthalen-1-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)-N,N-diphenyl-(2-[1,1′-biphenyl]vinyl)-4-amine (NSPI-TPA), 4′-(1-(2-methylnaphthalen-1-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)-N,N-diphenyl-(2-[1,1′-biphenyl]vinyl)-4-amine (MNSPI-TPA), 4-(2-(4′-(diphenylamino)-(2-[1,1′-biphenyl]vinyl)-4-yl)-1H-phenanthro[9,10-d]imidazol-1-yl)-1-naphthalene-1-carbonitrile (SPNCN-TPA) and 4-(2-(4-(9H-carbazol-9-yl)styryl)-1H-phenanthro[9,10-d]imidazol-1-yl)naphthalene-1-carbonitrile (SPNCN-Cz) were analyzed. The conjugation length in the emitters is not conducive to pure emission and hence, a molecular twisting strategy was adopted in NSPI-TPA, MNSPI-TPA, SPNCN-TPA and SPNCN-Cz to enhance pure emission. The emissive state (HLCT) of twisted D–π–A molecules containing both LE and CT (HLCT) states was tuned for high PL (η_PL) (LE) and high exciton utilization (η_s) (CT) efficiencies by replacing triphenylamine (strong donor) with carbazole (weak donor). Among strong donor compounds, namely, NSPI-TPA, MNSPI-TPA and SPNCN-TPA, the SPNCN-TPA-based device exhibited blue emission (451 nm) with CIE coordinates (0.15, 0.08), maximum current efficiency (η_c) of 2.32 cd A⁻¹, power efficiency (η_p) of 2.01 lm W⁻¹ and external quantum efficiency (η_ex) of 3.02%. The device with SPNCN-Cz emitter exhibited higher electroluminescence efficiencies than the SPNCN-TPA-based device, with pure blue emission (443 nm, CIE: 0.15,0.07), η_ex of 3.15%, η_c of 2.56 cd A⁻¹ and η_p of 2.45 lm W⁻¹.

SPNCN-Cz device exhibits η_ex (3.15%), η_c (2.56 cd A⁻¹), η_p (2.45 lm W⁻¹) with CIE (0.15, 0.07).     

A green sorbent for CO2 capture: α-cyclodextrin-based carbonate in DMSO solution

Cyclodextrin (α-CD)/KOH pellet dissolved in DMSO was utilized to capture CO₂. KOH has a dual function of enhancing the nucleophilicity of the hydroxyl groups on the α-CD rims and acting as a desiccant. ¹³C NMR spectroscopy provided evidence for the chemisorption of CO₂ through the formation of organic carbonate (RO-CO₂⁻·K⁺). This was supported by the spectral changes obtained using ex situ ATR-FTIR spectroscopy upon bubbling CO₂. Activation of α-CD with NaH or bubbling with ¹³CO₂ verified that chemisorption occurred solely via RO-CO₂⁻·K⁺ rather than inorganic bicarbonate. Volumetric gas uptake demonstrated a sorption capacity of 21.3 wt% (4.84 mmol g⁻¹). To the best of our knowledge, this is the highest chemisorption value reported to date for CD-based sorbents. DFT calculations of the Gibbs free energies indicated that the formation of RO-CO₂⁻·K⁺ was more favoured at the primary carbinol rather than its secondary counterpart.

α-Cyclodextrin dissolved in DMSO is a potential sorbent for CO₂ capture through the exclusive formation of ionic organic carbonate.     

Structure characterization and anticoagulant activity of a novel polysaccharide from Leonurus artemisia (Laur.) S. Y. Hu F

An acidic polysaccharide, named LAP-1, was extracted and isolated from Leonurus artemisia (Laur.), and was further purified with ion exchange chromatography and gel chromatography. The extraction conditions of the crude polysaccharides were optimized by single-factor experiments and response surface methodology. The primary structure of the purified polysaccharide was measured by FT-IR, GC-MS, and NMR. The results showed that LAP-1 was mainly composed of galacturonic acid (GalA), mannose (Man), xylose (Xyl), rhamnose (Rha), arabinose (Ara), glucose (Glc), galactose (Gal), fucose (Fuc), ribose (Rib), and glucuronic acid (GlcA) in the molar ratio of 8.74 : 3.45 : 1.02 : 1 : 2.11 : 5.60 : 4.73 : 1.08 : 1.09 : 1.47. Primary structure analysis results indicated that LAP-1 contained characteristic glycosyl linkages such as →1)-α-d-Manp, →1)-α-d-Glcp, →1)-α-d-Arap-(2→, →1)-β-d-Galp-(3→, →1)-β-d-Manp-(4→, →1)-β-d-Galp-(4→, →1)-β-d-Glcp-(4→, →1)-β-d-GalAp-(4→, →1)-β-d-GlcAp-(4→, →1)-β-d-Manp-(4,6→, →1)-β-d-Manp-(3,4→. The M_w/M_n (PDI), M_n, M_z and M_w of LAP-1 were determined to be 1.423, 6.979 × 10³ g mol⁻¹, 1.409 × 10⁴ g mol⁻¹, and 9.930 × 10³ g mol⁻¹ by HPSEC-MALLS-RID and DLS. SEM, TEM and AFM results indicated that LAP-1 was a highly branched structure. LAP-1 showed mild anticoagulant activity, low toxicity, and less spontaneous bleeding compared with heparin sodium. These results demonstrated the effective coagulation activity of Leonurus artemisia polysaccharides. Thus, the purified LAP-1 could be explored as a promising anticoagulant agent for the treatment of coagulation disorders.

An acidic polysaccharide, denoted LAP-1 was extracted, isolated and purified from Leonurus artemisia (Laur.), in addition to its structure and anticoagulant activity were explored.     

Efficient donor–acceptor host materials for green organic light-emitting devices: non-doped blue-emissive materials with dual charge transport properties

Comparative optical, electroluminescence and theoretical studies were performed for (E)-4′-(1-(4-(2-(1-(4-morpholinophenyl)-1H-phenanthro[9,10-d]imidazol-2-yl)vinyl)phenyl)-1H-phenanthro[9,10-d]imidazol-2-yl)-N,N-diphenyl-[1,1′-biphenyl]-4-amine (SMPI-TPA) and (E)-4-(4-(2-(4-(2-(4-(9H-carbazol-9-yl)phenyl)-1H-phenanthro[9,10-d]imidazol-1-yl)styryl)-1H-phenanthro[9,10-d]imidazol-1-yl)phenyl)morpholine (SMPI-Cz). These compounds show excellent thermal properties, dual charge transport properties and form thin films under thermal evaporation. Blue OLEDs (CIE: 0.16, 0.08) based on SMPI-TPA show efficient device performance (η_ex 6.1%; η_c 5.3 cd A⁻¹; η_p 5.2 lm W⁻¹) at low turn-on voltages. Both SMPI-TPA and SMPI-Cz were utilised as hosts for green OLEDs. The devices with SMPI-Cz (30 nm):5 wt% Ir(ppy)₃ exhibit maximum luminance of 20 725 cd m⁻², and η_c and η_p values of 61.4 cd A⁻¹ and 63.8 lm W⁻¹, respectively. In comparison, devices with SMPI-TPA (30 nm):5 wt% Ir(ppy)₃ exhibit high η_c and η_p values of 65.2 cd A⁻¹ and 67.1 lm W⁻¹, respectively. Maximum η_ex values of 19.6% and 23.4% were obtained from SMPI-TPA:Ir(ppy)₃ and SMPI-Cz:Ir(ppy)₃, respectively. These device performances indicate that the phenanthroimidazole unit is a tunable building unit for efficient carrier injection and it may also be employed as a host for green OLEDs.

SMPI-Cz:Ir(ppy)₃-based devices exhibit a luminance of 20 725 cd m⁻², η_c of 61.4 cd A⁻¹ and η_p of 63.8 lm W⁻¹.     

CD8β Increases CD8 Coreceptor Function and Participation in TCR–Ligand Binding

To study the role of CD8β in T cell function, we derived a CD8α/β⁻ (CD8^−/−) T cell hybridoma of the H-2K^d–restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8α alone or together with CD8β. All three hybridomas released interleukin 2 upon incubation with L cells expressing K^d–peptide derivative complexes, though CD8α/β cells did so more efficiently than CD8α/α and especially CD8^−/− cells. More strikingly, only CD8α/β cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab′ fragments of the anti-K^d α3 monoclonal antibody SF11.1.1 or substitution of K^d D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR–ligand binding on CD8α/β cells was ~5- and 20-fold more avid than on CD8α/a and CD8^−/− cells, respectively. SF1-1.1.1 Fab′ or K^d mutation D227K reduced the TCR photoaffinity labeling on CD8α/β cells to approximately the same low levels observed on CD8^−/− cells. These results indicate that CD8α/β is a more efficient coreceptor than CD8α/α, because it more avidly strengthens TCR–ligand binding.