Synthesis and photochemical properties of photoactivated antitumor prodrugs releasing 5-fluorouracil

A new family of antitumor prodrugs (1-3) of 5-fluorouracil (5-FU) possessing photolabile 2-nitrobenzyl chromophores have been designed and synthesized to investigate the efficiency and mechanism of photoactivated 5-FU release upon UV-irradiation at lambda(ex)= 365 nm. The photoactivated prodrug 3 derived from conjugation of 2 with a tumor-homing cyclic peptide Cys-Asn-Gly-Arg-Cys (CNGRC) was so designed as to manifest a tumor-targeting function.     

Polymerization of β-cyanopropionaldehyde. IV. Polymerization by the adducts of β-cyanopropionaldehyde with triethylaluminum

Adducts (X, Y, and Z) between triethylaluminum and β-cyanopropionaldehyde (CPA) have been prepared and characterized. It was found that an equimolar amount of triethylaluminum undergoes Grignard type addition reaction with aldehyde group of CPA to give aluminum alkoxide and that another equimolar quantity of triethylaluminum undergoes coordination with the nitrile group of CPA (adduct X, in which the molar ratio of CPA to aluminum is 1:2). The coordinated triethylaluminum in adduct X may be changed to aluminum alkoxide by the addition of further equimolar amount of CPA (adduct Y, molar ratio = 1:1); on the other hand, heating at 130°C affords mixtures of aluminum aldimine and aluminum ketenimine structures (adduct Z, molar ratio = 1:2). From the cryoscopic measurement, adduct Z may be regarded as a coordinated polymer joined through bridged structures I and II. In the polymerization of CPA at ?78°C, the stereoregularity of the resulting poly-(cyanoethyl)oxymethylene was found to increase in the order: X < triethylaluminum < Y < Z. The polymerizations with triethylaluminum, X, and Y are considered to be initiated by NCCH₂CH₂CH(C₂H₅)? O? Al(C₂H₅)₂. The degree of association of the species may influence the stereoregularity of the polymer.     

Initial mode of radical pair formation in n-hydrocarbons irradiated at 1.5 and 4.2 K

The ESR spectra of X-irradiated (at 1.5 and 4.2 K) single crystals of n-decane-d₂₂, n-decane-h₂₂ and their mixtures have been measured at 1.5 and 4.2 K. It is concluded that almost all alkyl radicals are inherently formed in pairs in a fairly random fashion and that the spacial distribution of the radicals depends on the irradiation temperatures. In the crystal of n-decane-d₂₂, a 1,3-carbon intrachain radical pair is identified together with a number of very close interchain pairs which are formed between almost all kinds of the first neighboring chains. The crystal of n-decane-h₂₂ gives considerably larger spacial distribution of radicals, indicating a remarkable mass effect on the radical pair formation.     

Syntheses of 4-(2-hydroperoxy-2,2-diarylethyl)-3,5-dimethylpyrazoles, 4-(2-hydroxy-2,2-diarylethyl)-3,5-dimethylpyrazoles and the related compounds

The reactions of 1,1-disubstituted ethenes with 2,4-pentanedione in the presence of manganese(III) acetate and atmospheric oxygen yielded 4-acetyl-6,6-diaryl-3-methyl-1,2-dioxan-3-ols. The latter gave 4-(2-hydroperoxy-2,2-diarylemyl)-3,5-dimethylpyrazoles by the reaction with hydrazines in methanol-acetic acid (1:1 v/v) at 50° in 15-77% yields, or 4-(2-hydroxy-2,2-diarylethyl)-3,5-dimethylpyrazoles by the reaction with hydrazines in methanol in 2-78% yields. The acid-catalyzed reaction of 4-(2-hydroperoxy-2,2-diarylethyl)-3,5-dimethylpyrazoles yielded 4-(aroylmethyl)-3,5-dimethylpyrazoles (15-55%) and 4-(2,2-diarylethenyl)-3,5-dimethylpyrazoles (9-29%).     

UV-Vis, NMR, and time-resolved spectroscopy analysis of photoisomerization behavior of three- and six-azobenzene-bound tris(bipyridine)cobalt complexes

The photoisomerization properties of tris(bipyridine)cobalt complexes containing six or three azobenzene moieties, namely, [Co(II)(dmAB)3](BF4)2 [dmAB = 4,4'-bis[3'-(4'-tolylazo)phenyl]-2,2'-bipyridine], [Co(III)(dmAB)3](BF4)3, [Co(II)(mAB)3](BF4)2 [mAB = 4-[3' '-(4' '-tolylazo)phenyl]-2,2'-bipyridine], and [Co(III)(dmAB)3](BF4)3, derived from the effect of gathering azobenzenes in one molecule and the effect of the cobalt(II) or cobalt(III) ion were investigated using UV-vis absorption spectroscopy, femtosecond transient spectroscopy, and 1H NMR spectroscopy. In the photostationary state of these four complexes, nearly 50% of the trans-azobenzene moieties of the Co(II) complexes were converted to the cis isomer, and nearly 10% of the trans-azobenzene moieties of the Co(III) complexes isomerized to the cis isomer, implying that the cis isomer ratio in the photostationary state upon irradiation at 365 nm is controlled not by the number of azobenzene moieties in one molecule but rather by the oxidation state of the cobalt ions. The femtosecond transient absorption spectra of the ligands and the complexes suggested that the photoexcited states of the azobenzene moieties in the Co(III) complexes were strongly deactivated by electron transfer from the azobenzene moiety to the cobalt center to form an azobenzene radical cation and a Co(II) center. The cooperation among the photochemical structural changes of six azobenzene moieties in [Co(II)(dmAB)3](BF4)2 was investigated with 1H NMR spectroscopy. The time-course change in the 1H NMR signals of the methyl protons indicated that each azobenzene moiety in [Co(II)(dmAB)3](BF4)2 isomerized to a cis isomer with a random probability of 50% and without interactions among the azobenzene moieties.     

Photochemistry of imidazolides. I. The photo-Fries-type rearrangement of N-substituted imidazoles.

A number of N-substituted imidazoles 1a–1i have been found to photo-isomerize to give the corresponding 2-substituted- and 4(or 5)-substituted imidazoles ( 2a–2i and 3a–3i ). The role of a dissociative path in these reactions has been demonstrated.     

Quantitative estimation of interaction between carbohydrates and concanavalin A by surface plasmon resonance biosensor

We measured the affinity of more than 20 sugars with concanavalin A (ConA) by an optical biosensor (surface plasmon resonance sensor) using asialofetuin (ASF) as an immobilized binding partner of ConA. We determined kinetic parameters of the effects of sugars on the dissociation of ConA from ASF quantitatively, and the structural requirements of the functional groups of sugars for binding with ConA. We found that the affinity of ConA for sugars is dependent on its conformation induced by interaction with the binding partner. In addition, the results showed that optical biosensor system is well mimics the interaction of ConA with sugars in biomembrane.     

Specific interaction between polyethylenimine and azo dyes carrying hydroxyl groups

The binding of acid azo dyes having phenolic hydroxyl groups such as orange I ( I ), orange II ( II ), chrome violet ( III ), 4-hydroxyazobenzene-4′-sulfonate ( IV ), and 2,4-dihydroxyazobenzene-4′-sulfonate ( V ) by polyethylenimine was studied by equilibrium dialysis and spectroscopic methods. The results obtained indicate that dyes ( III ) and ( V ) with two OH groups are bound much more strongly than dyes ( I ), ( II ), and ( IV ) with one OH group. Also polyethylenimine is far superior to any other polymers which have been examined, including bovine serum albumin, polyvinylpyrrolidone, and poly-L -lysine, in its ability to form complexes with these dyes ( III ) and ( V ). The OH groups involved participate preferentially in complex formation with polyethylenimine. The unusual affinity of polyethylenimine for the dyes carrying OH groups is discussed.     

Reaction of 1-alkylthioisoquinolinium salts with active methylene compounds

2-Alkyl-1-alkylthioisoquinolinium salts were readily prepared from 2-alkyl-1(2H)-isoquinolones via 2-alkyl1(2H)-thioisoquinolones in two steps. Under mild conditions, the reaction of 2-alkyl-1-alkylthioisoquinolinium salts with active methylene compounds in the presence of sodium hydride afforded 2-alkyl-1-(substituted methylene)iso-quinolines in good yields. Pyrrolo[2,1-a]isoquinolines were synthesized by the cyclization of 2-benzyl-1-(substituted methylene)isoquinolines using acetic anhydride.     

Production of polyacrylonitrile particles by precipitation polymerization in supercritical carbon dioxide

Polyacrylonitrile particles were produced by precipitation polymerization of acrylonitrile (AN) without any colloidal stabilizer in supercritical carbon dioxide as a polymerization medium at about 30 MPa for 24 h at 65 °C at different initiator concentrations (0.8–45.2 mmol/l) and at different AN concentrations (10–40% w/v). An increase in the initiator concentration led to increases in the conversion and in the degree of coagulation and to a decrease in the molecular weight. At AN concentration of 20% w/v, micron-sized, relatively monodisperse polyacrylonitrile particles with clean and uneven surfaces were produced.