An Ethylenediamine‐based Switch to Render the Polyzwitterion Cationic at Tumorous pH for Effective Tumor Accumulation of Coated Nanomaterials

Polyzwitterions are employed as coating polymers for biomaterials to induce an antifouling property on the surface. Fine‐tuning the betaine structure switches the antifouling property to be interactive with anionic tissue constituents in response to a tumorous pH gradient. The ethylenediamine moiety in the carboxybetaine enabled stepwise protonation and initiated the di‐protonation process around tumorous pH (6.5). The net charge of the developed polyzwitterion (PGlu(DET‐Car)) was thus neutral at pH 7.4 for antifouling, but was cationic at pH 6.5 for interaction with anionic constituents. Quantum dots coated with PGlu(DET‐Car) exhibited comparable stealth and enhanced tumor accumulation relative to the PEG system. The present study provides a novel design of smart switchable polyzwitterion based on a precise control of the net charge.     

A Water‐Soluble Warped Nanographene: Synthesis and Applications for Photoinduced Cell Death

Nanographene, a small piece of graphene, has attracted unprecedented interest across diverse scientific disciplines particularly in organic electronics. The biological applications of nanographenes, such as bioimaging, cancer therapies and drug delivery, provide significant opportunities for breakthroughs in the field. However, the intrinsic aggregation behavior and low solubility of nanographenes, which stem from their flat structures, hamper their development for bioapplications. Herein, we report a water‐soluble warped nanographene (WNG) that can be easily synthesized by sequential regioselective C?H borylation and cross‐coupling reactions of the saddle‐shaped WNG core structure. The saddle‐shaped structure and hydrophilic tetraethylene glycol chains impart high water solubility to the WNG. The water‐soluble WNG possesses a range of promising properties including good photostability and low cytotoxicity. Moreover, the water‐soluble WNG was successfully internalized into HeLa cells and promoted photoinduced cell death.     

A truncated palytoxin analogue,palytoxin carboxylic acid,isolated as an insecticidal compound from the red alga, Chondria armata

Palytoxin (PTX) has been widely studied owing to its outstanding toxic properties and complex structural features. It is a great challenge to identify and isolate analogues of PTX from various organisms and reveal their physiological activities. We previously reported the isolation of PTX as an insecticidal compound from the red alga, Chondria armata. In this study, we investigate another active compound from C. armata, which has similar toxicity and chromatographic behavior as PTX. Our detailed structural analysis reveals that this compound is palytoxin carboxylic acid. We characterized its physicochemical properties and conducted extensive NMR studies. This analogue has a structure devoid of the terminus of PTX, such that its presence in the alga implies the role of symbiotic microorganisms in marine ecosystems.     

13C-selective infrared multiple-photon decomposition study of CBrClF2

The infrared multiple-photon single-frequency decomposition (IRMPD) of CBrClF₂ was examined as functions of laser wavenumber, laser fluence, and partial pressure of CBrClF₂. The initial step was the scission of a C-Br bond. In the presence of O₂ the carbon-containing product was CF₂O and its subsequent hydrolysis gave CO₂. The initial dissociation was highly ¹³C selective at wavenumbers below 1014 cm^–1. CBrClF₂ decomposed at relatively low fluences as compared to CHClF₂. However, the decomposition yield rapidly decreased with increasing pressure. In the large-scale irradiation experiment using about 8 J pulse at 1 Hz, we obtained a carbon yield of 0.41 mol per pulse at a ¹³C-atom fraction of 17% for a mixture of 10 Torr CBrClF₂ and 10 Torr O₂, and a carbon yield of 0.17 mol per pulse at a fraction of 29% for a mixture of 20 Torr CBrClF₂ and 20 Torr O₂. The IRMPD of CHClF₂ gave a carbon yield of 0.18 mol per pulse at 48% for 10 Torr neat CHClF₂ and yield of 0.25 mol at 52% for 20 Torr CHClF₂. The large-scale irradiation experiment was also carried out for mixtures of CBr₂F₂ and O₂. CHClF₂ is the most productive of ¹³C.     

Studies on the constituents of Leonurus sibiricus L

Two new furanoditerpene-lactones, LS-1 (1) and LS-2 (2), were isolated along with four known furanoditerpene-lactones 3, 4, 5 and 6 from the aerial part of Leonurus sibiricus L. The structures of the new compounds were determined by spectroscopic means. Compounds 1-6 isolated here exhibited moderate cytotoxic activity (IC(50)=50-60 microg/ml) against leukemia cells (L 1210) in tissue culture.     

Synthesis of polypropionamide-ureas from N-mesyloxysuccinimide and diamines

A series of polypropionamide-ureas was synthesized by the polymerization of N-mesyloxysuccinimide with diamines in polar aprotic solvents in the presence of acid acceptors. The polymerization proceeded through the formation of ring-opened adducts, followed by elimination and rearrangement yielding β-isocyanatopropionamide derivatives, which in turn were polymerized to afford polypropionamide-ureas. These polymers had inherent viscosities in the range of 0.1–0.2. Polymers having aliphatic chains which were fusible below 240°C were soluble in acidic solvents, whereas those with aromatic residues dissolved in polar aprotic solvents. Marked decomposition of the polyamide-ureas under thermogravimetric analysis generally occurred at around 320°C under nitrogen.     

Synthesis of polyamides from active diacyl derivatives of 3-hydroxy-1,2-benzisoxazole and diamines under mild conditions

New active diesters and diamides derived from 3-hydroxy-1,2-benzisoxazole were prepared for use in polyamide synthesis. The active esters and amides reacted readily with amines to give quantitative yields of amides. The high reactivity to these active esters and amides was discussed in relation to the electon-withdrawing effect of the leaving group and intramolecular general-base catalysis. Solution polycondensation of new active diesters and diamides with aliphatic and aromatic diamines proceeded slowly under mild conditions to produce polyamides with inherent viscosities up to 1.5.     

Proteomic analysis of Epstein-Barr virus-transformed human B-lymphoblastoid cell lines before and after immortalization

Infection of human B lymphocytes with Epstein-Barr virus (EBV) induces proliferative B-lymphoblastoid cell lines (LCLs). However, the majority of EBV-transformed LCLs are mortal and unable to avoid cellular senescence. In our previous experiment, three immortalized LCLs were established by passages of EBV-transformed LCLs for nearly five years accompanied by strong telomerase activity. In the present study, proteomic profiles of these three LCLs were analyzed comparatively at the early and the late passages of cell culture, and a protein spot was found which most significantly decreased with the immortalization in two LCLs. The expression of the protein in the third LCL was suppressed at 17 population doubling level (PDL), already suggesting that part of the immortalization process had been initiated before 17 PDL. The protein was assigned to ssp7001 (16.3 kDa, pI 6.0) by referring to our TMIG-2DPAGE proteome database. The protein was transferred onto a polyvinylidene difluoride (PVDF) membrane and digested with lysilendopeptidase to perform peptide mass fingerprinting by nanoelectrospray ionization mass spectrometry (nano-ESI-MS). Subsequent MS-Fit database search indicated that ssp7001 is a phosphoprotein stathmin. This speculation was confirmed by the tandem MS (MS/MS) analysis in a Q-Tof system and by Edman degradation microsequencing.