Cellular uptake and photocytotoxicity of glycoconjugated porphyrins in HeLa cells

Thirty-two glycoconjugated porphyrins were synthesized by a modification of Lindsey method in the presence of Zn(OAc)(2).2H(2)O as a template. The Zn(2+) ion template strategy improved the yield about three-fold in the case of meta-substituted tetraphenylporphyrins. In addition, free-base porphyrins were obtained almost quantitatively by demetalation with 4 M HCl. Sixteen deacetylated glycoconjugated porphyrins were tested as candidate photodynamic therapy (PDT) drugs using HeLa cells. Most of the deacetylated glycoconjugated porphyrins showed higher cellular uptake than tetraphenylporphyrin tetrasulfonic acid (TPPS), and 5,10,15,20-tetrakis[4-(beta-D-arabinopyranosyloxy)phenyl]porphyrin (p-5d) in particular showed 18.5-fold higher uptake than TPPS. The photocytotoxicity of 5,10,15,20-tetrakis[4-(beta-D-glucopyranosyloxy)phenyl]porphyrin (p-5a), p-5d and TPPS was examined with HeLa cells, using a light dose of 16 J/cm(2). These photosensitizers had no cytotoxicity in the dark, but their photocytotoxicity increased in the order of TPPS < p-5a < p-5d. These results suggest p-5d is a good candidate for a PDT drug.     

Efficacy of spectral presaturation of inversion recovery in evaluating delayed myocardial enhancement

OBJECTIVE: Delayed myocardial enhancement is caused by a variety of cardiovascular diseases. The extent of the enhanced area has been examined by the inversion recovery (IR) method, whereby at the inversion time (TI), normal myocardium shows a low signal intensity. In this sequence, as pericardial fat shows a very high intensity, a delayed enhancement just below the pericardium may be indistinct. To improve the accuracy of delayed myocardial enhancement, we employed the spectral presaturation of inversion recovery (SPIR) method. MATERIALS AND METHODS: Thirty-five patients with symptoms of cardiovascular disease aged between 36 and 80 years old (mean age, 62 years old) were investigated. Thirty were men and five were women. Inversion recovery and SPIR images were obtained 25 min after initial administration of a gadolinium-based contrast material. Each TI, when the signal intensity of the normal myocardium was null, was determined by images obtained at serial different TIs. A radiologist and a cardiologist examined each image by a consensus reading. The extent of myocardial enhancement was described as none, subendocardial, transmural and a random pattern in each case. Images were ranked over three levels and were based on whether myocardial enhancement could be easily detected or whether the contour of the myocardium was visualized precisely. Student's t-test was conducted to compare the quality of two sequences in all patients and in 22 patients who showed delayed myocardial enhancement. RESULTS: The imaging quality in evaluating delayed myocardial enhancement in all patients was superior with IR compared with SPIR, although it was not statistically significant. The imaging quality in the patients with delayed myocardial enhancement was similar between SPIR and IR. SPIR was superior to the IR sequence in two of the four patients who exhibited transmural enhancement. CONCLUSION: SPIR exhibited equivalent image quality to IR in evaluating delayed myocardial enhancement. As it has the potential advantage in patients with rich adipose tissue surrounding the myocardium, it can be an alternative sequence to evaluate myocardial viability.     

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.     

Aminolithiation–arylation consecutive cyclization of N-(2-fluorophenyl)methylaminoalkylstyryls giving aryl-substituted pyrido[1,2-b]isoquinolines

Aminolithiation–arylation tandem cyclization of N-(2-fluorophenyl)methylaminoalkylstyryls proceeded smoothly to give hexahydro-2H-pyrido[1,2-b]isoquinoline using a stoichiometric amount of n-BuLi with high trans selectivity. The arylation reaction was highly accelerated by the addition of HMPA. Both pyrido- and pyrrolo-[1,2-b]isoquinoline were successfully constructed by this tandem reaction.     

Synthesis and properties of [9]cyclo-1,4-naphthylene: a π-extended carbon nanoring

The first synthesis of a π-extended carbon nanoring, [9]cyclo-1,4-naphthylene ([9]CN), has been achieved. Careful structure-property analyses uncovered a number of unique features of [9]CN that are quite different from those of [9]CPP, a simple carbon nanoring.     

Steric tuning of C2-symmetric chiral N-heterocyclic carbene in gold-catalyzed asymmetric cyclization of 1,6-enynes

Steric tuning of C₂-symmetric chiral N-heterocyclic carbene (NHC) was performed in Au(I)-catalyzed asymmetric cyclization of 1,6-enyne. Higher enantioselectivity was realized when chiral NHC–AuCl/AgSbF₆ catalysts whose N-substituent on the NHC overlays the Au–Cl bond was utilized.     

Combined experimental and theoretical studies on the photophysical properties of cycloparaphenylenes

We studied the UV-vis absorption and fluorescence in solution/solid states of [n]cycloparaphenylene ([n]CPP: n = 9, 12, 14, 15, and 16), and conducted theoretical studies to better understand the experimental results. The representative experimental findings include (i) the most intense absorption maxima (λ(abs1)) display remarkably close values (338-339 nm), (ii) the longest-wavelength absorption maxima (λ(abs2)) are blue-shifted with increasing the ring size (395 → 365 nm), (iii) the emission maxima (λ(em)) are blue-shifted with increasing the ring size (494 → 438 nm for longest-wavelength maxima), (iv) the fluorescent quantum yields (Φ(F)) in solution are high (0.73-0.90), (v) the fluorescence lifetimes (τ(s)) of [9]- and [12]CPP are 10.6 and 2.2 ns, respectively, and (vi) the Φ(F) values slightly increase in polymer matrix but significantly decrease in the crystalline state. According to TD-DFT calculations, the longest-wavelength absorption (λ(abs2)) corresponds to a forbidden HOMO → LUMO transition and the most intense absorption (λ(abs1)) corresponds to degenerate HOMO - 1 → LUMO and HOMO → LUMO + 1 transitions with high oscillator strength. The interesting and counterintuitive optical properties of CPPs (constant λ(abs1) and blue shift of λ(abs2)) could be ascribed mainly to the ring-size effect in frontier molecular orbitals (in particular the increase of the HOMO-LUMO gap as the number of benzene rings increases). On the basis of comparative calculations using hypothetical model geometries, we conclude that the unique behavior of HOMO and LUMO of CPPs is due mainly to their lack of a conjugation length dependence in combination with a significant bending effect (particularly to HOMO) and a torsion effect (particularly to LUMO).     

Asymmetric radical addition of ethers to enantiopure N-p-toluenesulfinyl aldimines, mediated by dimethylzinc-air

Asymmetric radical addition of ethers to enantiopure aromatic N-p-toluenesulfinyl aldimines has been achieved. The requisite radicals were generated by dimethylzinc-air. Lewis acid activation of the N-p-toluenesulfinyl aldimines followed by radical addition gives a mixture of sulfinamide and sulfonamide products. Subsequent treatment of the mixture with dry m-CPBA affords the sulfonamide product in enantiomerically enriched form. [reaction: see text]     

A ternary complex reagent for an asymmetric Michael reaction of lithium ester enolates with enoates

A lithium ester enolate was activated by both a chiral etheral ligand and a lithium amide to form a ternary complex reagent that reacted with enoates giving the corresponding Michael addition products in reasonably high enantioselectivity of up to 97% ee.