New anti-tumor agents. 3. Phenolic benzopyran lactone and amine derivatives

2-Aminopyridine, sesamol and 4-hydroxy-3,5-dimethoxybenzaldehyde condense to form a Mannicb base 3b which reacts with tetronic acid to yield lactone 4c . Cyclization of 4c yields the benzopyran lactone 1b ; this inhibits growth of tumors in NCI in vitro tests. Alkaline hydrolysis of acetylated and methylated intermediate lactones, e.g. 4e , in the presence of acetone leads to the formation of novel lactones, e.g., of type 6 , which incorporate the acetone nucleus. Compound 6 is of interest since it inhibits tumor growth in vitro and has been selected by NCI for ongoing in vivo testing with human cancers. Heating 3b with mixtures of propionaldehyde and secondary amines such as morpholine leads to 3-methylbenzopyrans containing the amine nucleus, e.g. 7b. Unlike 3,4,5-trimethoxyphenyl compounds, e.g. 7a , phenolic analogs of type 7b do not inhibit growth of tumors in vitro.     

New anti-tumor agents. 2. Benzopyranylamine compounds

Pyrrolidine, morpholine and piperidine derived Mannich bases of types 1–3 react with acetone, propionaldehyde and butyraldehyde to form 2-methyl and 3-methylbenzopyrans of types 4–8 . Hydrolysis of these benzopyrans yields alcoholic benzopyrans which readily condense with a variety of amine, aniline and hydrazine derivatives to form diverse isomeric benzopyrans of types of 9 and 10 . The benzopyrans 4–9 which contain a 3,4,5-trimethoxyphenyl ring are active anti-tumor agents, particularly against human breast, CNS and colon cancer cell lines, total growth inhibition of these tumors often occurring in vitro at concentrations as low as 10⁻⁵-10⁻⁶ moles/1. Because of their in vitro activities and unusual structures a number of these benzopyrans have been selected for in vivo Xenograft testing against breast and other susceptible human cancers.     

Cyclizations of the C10 Fatty Acids from the Mandibulary Glands of the Honeybee Apis mellificaL.: Queen substance and royal jelly acid

Series of assays have been performed to cyclize the two main C₁₀ aliphatic acids, (E)-9-oxo-dec-2-enoic acid ( 3 ) (queen substance) and (E)-10-hydroxy-dec-2-enoic acid ( 7 ) (royal jelly acid) produced by the mandibulary glands of the honeybee Apis mellifica L . Queen substance 3 , resistant to thermocyclization, was cyclized by the action of polyphosphoric acid to the fulvene ketone 5 . Triphenylphosphinediethyl azodicarboxylate treatment of royal jelly acid 7 mainly furnished the dilactide 6 together with a series of cyclic oligomers up to the pentamer. Attempts to favour the formation of the lactone 11 through other conditions failed, and thus the reaction does not seem suitable for the preparation of lactones using α, β-unsaturated hydroxy acids. Substances 3 , 7 , 12 , 13 , 14 , 15 , were submitted to in vitro antibacterial as well as growth inhibition tests but all results were negative at the concentrations reported.     

Synthesis and biological activities of substituted dihydrobenzo[h]-pyrimido[4,5-b]quinolines as tetracyclic 5-deaza nonclassical folates

Novel tetracyclic compounds 1–4 have been synthesized via a regiospecific cyclocondensation reaction between substituted 6-aminopyrimidines 5– 7 and chlorovinyl aldehydes 13 and 14 . The linear structures of these compounds were established by ¹H nmr and ¹³C nmr spectral data and also by synthesis of the compounds via an unambiguous route. The growth of Manca human lymphoma cells was inhibited 50% by 1 and 4 at 4.5 × 10^?6 M and 1.2 × 10^?6 M respectively. These compounds also inhibited human dihydrofolate reductase (DHFR)by 50% at 4.4 × 10^?6 M and 1.4 × 10^?6 irrespectively and L. casei DHFR at 1.9 × 10^?5 M and 1.1 × 10^?5 M respectively. Compound 16 , a positional isomer of 1 , was the most potent of the compounds studied, it inhibited the growth of Manca human lymphoma cells by 50% at 9 × 10^?8 M. The IC₅₀ values of 16 for the inhibition of human DHFR and L. casei DHFR were 8 × 10^?8 M and 1.9 × 10^?5 M respectively.     

Photochemische Erzeugung und Reaktionen des Benzonitril-benzylids. 42. Mitteilung über Photoreaktionen

Photochemical Generation and Reactions of Benzonitrile-benzylide The low temperature irradiation of 2,3-diphenyl-2H-azirine ( 1 ) in DMBP-glass at ?196° has been reinvestigated. It was possible to convert 1 nearly quantitatively into the dipolar species benzonitrile-benzylide ( 3 , Φ₃ = 0,78), which exhibits UV.-absorptions at 344 (? = 48000) and 244 nm (? = 28500) (Fig. 1, Tab. 1). Irradiation of 3 with 345 nm light at ?196° resulted in almost complete reconversion to the azirine 1 (Φ = 0,15; Fig. 2). When the solution of 3 in the DMBP-glass was warmed up to about ?160° a quantitative dimerization to 1,3,4, 6-tetraphenyl-2,5-diaza-1,3,5-hexatriene ( 8 ) occurred. This proves that 8 is not only formed by the indirect route 3 + 1 → 7 \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\longrightarrow }\limits^{hv} $\end{document} 11 → 8 known before (Scheme 1), but also by dimerization of 3 either by direct head to head coupling or via the intermediate e (p. 2675), followed by a fast thermal hydrogen transfer reaction. The occurrence of the dipolar intermediate 11 in the photochemical conversion of the bicyclic compound 7 to 8 could also be demonstrated by low temperature experiments: On irradiation at ?196° 7 gave the cherry red dipolar intermediate 11 (λ_max = 520 nm), which at ?120° isomerizes to 8 . It should be noted, that neither 7 nor 11 are formed by dimerization reactions of 3 . Experiments carried out at room temperature demonstrate, that both processes for the formation of 8 may compete: Irradiation of a solution of 1 (DMBP, c = 8 × 10^?4 to 5 × 10^?3M ) with 350 nm light of high intensity (which does not excite the bicyclic compound 7 ) leads to a relative high photostationary concentration of the dipolar species 3 . Under these conditions the formation of 8 is due to dimerization of 3 (Φ₈ = 0,19). With low light intensity only a very low stationary concentration of 3 can be obtained. Therefore the reaction of 3 with 1 , leading to the bicyclic intermediate 7 , becomes now predominant (Φ_?1 = 1,55, which corresponds with the expected value of 2 × 0,8). Irradiation of 1 at ?130° with 350 nm light of high intensity gives 8 with a quantum yield of 0,44. This is in agreement with the theoretical value Φ₈ = 0,4 for an exclusive formation of 8 by dimerization of 3 . The lower quantum yield for the formation of 8 at room temperature makes probable that under these conditions 3 not only dimerizes to 8 , but also to another, so far unidentified dimer, e.g. 2,3,5,6-Tetraphenyl-2,5-dihydropyrazine. By flash photolysis of a solution of 1 (cyclohexane, c = 10^?4M , 25°) the disappearance of 3 could directly be measured by UV.-spectroscopy: At relative high concentrations (c ≥ 10^?7M ) 3 disappeared according to a second order reaction with the rate constant k = 5 × 10⁷M ^?1S ^?1. At lower concentrations (c ≤ 10^?7M) the rate of disappearance of 3 follows first order kinetics. The rate constant of this pseudo first order reaction ( 3 + 1 → 7 ) has been determined to be 1 → 10⁴M^?1S^?1. Using Padwa's table of relative rates for the cycloaddition of the dipolar species 3 to various dipolarophiles, including the azirine 1 , an absolute rate constant of k ≈ 8 × 10⁸M ^?1S ^?1 for the addition of 3 to the most active dipolarophile fumaronitrile could be estimated. In cyclohexane at room temperature, the diffusion controlled rate constant equals 6,6 × 10⁹M ^?1S ^?1. In Table 1 the UV.-maxima of several nitrile-ylides, among them a purely aliphatic one, are given.     

Oxidation studies with peroxomonophosphoric acid. II. A kinetic and mechanistic study of dimethyl sulfoxide oxidation in acid and alkaline media

The kinetics of dimethyl sulfoxide (DMSO) oxidation by peroxomonophosphoric acid (PMPA) in aqueous medium at 308 K and I = 0.4 mol/dm³ follow the rate expressions In the pH range from 0 to 2, where k₁ and k₂ are 5.092 × 10^?1 dm³/mol sec and ? 0, respectively; in the pH range from 4 to 7, where k₂ = 8.127 × 10^?3 and k₃ = 2.90 × 10^?3 dm³/mol sec; and in the pH range from 10 to 13.6, where k₄ ? 0, and k₅ = 3.08 × 10^?2 dm³/mol sec. The reaction is interpreted in terms of mechanisms involving an electrophilic and a nucleophilic attack of the peroxomonophosphoric acid species, respectively, in acid and alkaline regions, on the sulfur atom of the sulfoxide molecule giving rise to S-type transition states followed by oxygen-oxygen bond fission to form the products.     

Purines. XIV. Synthesis and properties of 8-nitroxanthine and its N-methyl derivatives

Xanthine ( 1 ) and its N-methyl derivatives 2–16 have been nitrated to the corresponding 8-nitro derivatives 17–32 under different reaction conditions. Nitration in glacial acetic acid with nitric acid works well with the N-7 unsubstituted and some of the 9-methylxanthines, respectively, whereas the 7-methylxanthine derivatives react best with nitronium tetrafluoroborate in sulfolane or glacial acetic acid. The 8-nitro group can be displaced nucleophilically to form 8-chloro-, 33, 34 , 8-ethoxy-, 35,36 , and uric acid derivatives 37–40 , respectively. The newly synthesized 8-nitroxanthines have been characterized by elemental analyses, pK-determinations and uv and ¹H-nmr spectra.     

Heliotropium bacciferum Forssk. (Boraginaceae) extracts: chemical constituents,antioxidant activity and cytotoxic effect in human cancer cell lines

Heliotropium bacciferum (Boraginaceae) is a perennial herb, growing in the Bechar region of Algeria, where it is traditionally used for skin diseases and tonsillitis. Herein, we report the isolation and characterization of sixteen secondary metabolites from the aerial part extracts. They include a sterol (1), megastigman type nor-isoprenoids (2, 3, 4, 6, 8, 10), C-11 terpene lactones (5 and 9), and a monoterpene (7) from the chloroform extract (HB-C); monoterpene glucoside (14), and phenolic compounds (11–13, 15, 16) from the methanol one (HB-M). Their structures were elucidated by spectroscopic methods including 1D and 2D NMR experiments, and ESIMS analysis. HB-M showed a significant and concentration dependent scavenging activity in vitro against the radicals DPPH and ABTS, related to the phenol derivatives (11–13, and 15–16), and HB-C inhibited the growth of colon cancer cell lines, mainly for the presence of the antiproliferative C-11 terpene lactones (5 and 9).     

Sensitive Voltammetric Response of p‐Nitroaniline on Single‐Wall Carbon Nanotube‐Ionic Liquid Gel Modified Glassy Carbon Electrodes

An ionic liquid (i.e., 1‐butyl‐3‐methylimidazolium hexafluorophosphate, BMIMPF₆)‐single‐walled carbon nanotube (SWNT) gel modified glassy carbon electrode (BMIMPF₆‐SWNT/GCE) is fabricated. At it the voltammetric behavior and determination of p‐nitroaniline (PNA) is explored. PNA can exhibit a sensitive cathodic peak at ?0.70 V (vs. SCE) in pH 7.0 phosphate buffer solution on the electrode, resulting from the irreversible reduction of PNA. Under the optimized conditions, the peak current is linear to PNA concentration over the range of 1.0×10^?8–7.0×10^?6 M, and the detection limit is 8.0×10^?9 M. The electrode can be regenerated by successive potential scan in a blank solution for about 5 times and exhibits good reproducibility. Meanwhile, the feasibility to determine other nitroaromatic compounds (NACs) with the modified electrode is also tested. It is found that the NACs studied (i.e., p‐nitroaniline, p‐nitrophenol, o‐nitrophenol, m‐nitrophenol, p‐nitrobenzoic acid, and nitrobenzene) can all cause sensitive cathodic peaks under the conditions, but their peak potentials and peak currents are different to some extent. Their peak currents and concentrations show linear relationships in concentration ranges with about 3 orders of magnitude. The detection limits are 8.0×10^?9 M for p‐nitroaniline, 2.0×10^?9 M for p‐nitrophenol, 5.0×10^?9 M for o‐nitrophenol, 5.0×10^?9 M for m‐nitrophenol, 2.0×10^?8 M for p‐nitrobenzoic acid and 8.0×10^?9 M for nitrobenzene respectively. The BMIMPF₆‐SWNT/GCE is applied to the determination of NACs in lake water.     

Photochemische Reaktionen. 62. Mitteilung [1]. Die Photofragmentierung von O-acetyljervin

On ultraviolet irradiation O-acetyljervine ( 1 ) is subjected to several parallel fragmentations. From the complex reaction mixtures obtained in a variety of solvents (dioxan, tetrahydrofuran, acetonitrile, iso-octane, benzene) the major alicyclic products 6 – 8 and the heterocyclic compounds 12 – 16 have been isolated. Products 6 – 8 undergo further photochemical changes, e.g., decarbonylation of 7 to 9 and hydrolytic cleavage of 8 to 10 . These photofragmentations are initiated almost specifically upon selective π → π* excitation at 2537 Å with a quantum yield of Φ²⁵³⁷ = 0.145 for conversion of starting material. Reaction upon irradiation in the long-wavelength n → π* absorption band is very much less efficient (Φ³⁶⁶⁰ = 0.611 · 10^?3, both determinations for O-trimethylsilyl-jervine ( 2 ) in tetrahydrofuran). A high degree of photostability is observed also at 2537 Å on N-protonation of O-acetyljervine ( 1 ) in acetic acid. Furthermore, reactivity is greatly reduced for the N-methyl ( 3 ) and N-acetyl ( 4 ) derivatives in neutral solvents at 2537 Å. N-Chloro-O-acetyljervine ( 5 ) in dioxan at 2537 Å gave preferentially O-acetyljervine hydrochloride.     

A sensitive method for simultaneous determination of four macrolides by CE with electrochemiluminescence detection and its applications in human urine and tablets

A sensitive method for simultaneous determination of azithromycin (AZI), acetylspiramycin (ACE), erythromycin (ERY), and josamycin (JOS) was developed by CE coupled with electrochemiluminescence detection with Ru(bpy)₃²⁺. The parameters related to separation and detection were investigated in detail. The four macrolides were well separated and detected within 6 min under the optimized conditions. The LOD (S/N=3) of AZI, ACE, ERY, and JOS were 1.2×10^?9, 7.1×10^?9, 3.9×10^?8 and 9.5×10^?8 mol/L, respectively. The LOQ (S/N=10) of AZI, ACE, ERY, and JOS in human urine were 8.2×10^?8, 2.5×10^?7, 8.9×10^?7 and 1.2×10^?6 mol/L, respectively. The recoveries of the four macrolides in human urine and pharmaceutical tablet samples were 85.0–104.0% at different concentration levels.     

Synthesis of Pyrrolidine Analogues of N-Acetylneuraminic Acid as Potential Sialidase Inhibitors

The pyrrolidine derivatives 3 , 4 , and 5 were prepared from the methyl ester 7 of Neu2en5Ac via lie pyrrolidine-borane adduct 33 . They inhibit Vibrio cholerae sialidase competitively with K_i = 4. 4 10^?3 M, 5. 3 10^?3 M, and 4. 0 10^?2 M, respectively. Benzylation of 7 gave the fully O-benzylated 8 besides 9, 10 , and 11. Ozonolysis and reduction with NaBH₄ of 8 and 9 gave the 1, 4-diols 12 and 15 , the hydroxy acetates 13 and 16 , and the furanoses 14 and 17 (Scheme 1), respectively. The diol 12 was selectively protected (→ 19 → 20 → 23 ) and transformed into the azide 27 by a Mitsunobu reaction. Selective base-catalysed deprotection of the diacetate 22 , obtained from 12 , was hampered by an easy acetyl-group migration. The mesylate 28 proved unstable. The azide 27 was transformed via 29 into the ketone 30 (Scheme 2). Hydrogenation of 30 gave the dihydropyrrole 31 and, hence, the pyrrole 32. The adduct 33 was obtained from 30 by a Staudinger reaction (→31) and reduction with LiBH₄/HBF⁴. It was transformed into the pyrroudine 34 . The structure of 34 was established by X-ray analysis. Reductamination of the pyrrolidine-borane adduct with glyoxylic acid gave 40 and, hence, 3. N-Alkylation afforded 44 and, hence, the phosphonate 4. The acid 5 was obtained from 33 by acylation (→ 47 ) and deprotection (Scheme 4).     

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 32

The G[s ]G dinucleoside 6 and the G[s ]G* dinucleoside 8 were prepared by alkylation of the guanosine thiols derived from 2 and 5 , respectively, by the C(8)‐chloromethylated guanosine 4 that was obtained from alcohol 3 . Dinucleosides 6 and 8 were deacylated to 7 and 9 , and fully deprotected to 10 and 11 , respectively. The G[n ]G dinucleoside 16 was obtained by reductive amination of aldehyde 13 with an iminophosphorane derived from azide 14 and deprotection of the resulting dimer 15 . In the solid state of 6 , and in a solution of 6 and 8 in CDCl₃, H? N(1/I) and H? N(1/II) are engaged in intramolecular H‐bonds to the C?O of the isobutyryl protecting groups, and HN of the isobutyryl group of unit I forms an interresidue, intramolecular H‐bond to N(7/II), leading to a syn orientation of the nucleobase at unit I, to a tg orientation of the sulfanyl moiety, and to an orthogonal orientation of the nucleobases, preventing any base pairing. The silylated and isopropylidenated dinucleosides 7 and 9 are present in DMSO solution as solvated monoplexes. Broad ¹H‐NMR signals of the nucleosides 7 and 16 in CHCl₃ solution evidence equilibrating G‐quadruplexes. The quadruplex formation of 7 and 16 was established by ¹H‐NMR spectroscopy (only of 16 ), vapour pressure osmometry, mass spectrometry, and CD spectroscopy. The C(6(I))‐hydroxymethylated analogue 9 in CDCl₃ and the fully deprotected dinucleosides 10 and 11 in H₂O form only weakly π? π stacked associates, but no G‐quadruplexes, as evidenced by CD spectroscopy.     

Effects of sublethal levels of tributyltin chloride on a new toxicity test organism,Liza saliens (osteichthyes,mugilidae): a histological study

The histopathological effects of 10^?7 and 10^?9 M tributyltin(IV)chloride,TBTCl, solutions on different Liza saliens organs have been studied by light microscope. The fish were sacrificed after 3–4 h incubation in 10^?7 M TBTCl solution or after 15 days incubation in 10^?9 M solution. The observed histopathological changes were dose‐ and time‐dependent. The 10^?7 M TBTCl concentration resulted in major damage to the gill epithelium, indicating that TBTCl primarily interfered with the respiration, osmoregulation, acid balance and nitrogenous waste excretion processes. After incubation in 10^?9 M TBTCl solution the fish lived 20 or more days, but many of the organs were altered. Thymus atrophy, reduced spleen and altered head kidney were observed. These histological results indicated that TBTCl interfered with organ immunodefense and altered main metabolic pathways in Liza saliens. The presence of melano‐macrophage centers, only in TBT‐treated liver and spleen, can be considered a tool to facilitate, with other biomarkers, the detection of alterations by toxicants. Regarding the pancreas activity in 10^?7 M solutions, it has been noted that, in the exocrine cells, very few zymogen granules were still present and the Langerhans islets were more altered. In 10^?9M solution the exocrine pancreatic cells had no granules and the islet cells presented degenerative alterations. In addition, TBTCl, which altered the pancreas and gonad morphology, could again be considered an endocrine disrupter even if biochemical data are still necessary. Finally, the Liza saliens juveniles could be considered an interesting biological model for experiments with contaminants, due to their ease of adaptation to experimental conditions and food chain position. Copyright © 2005 John Wiley & Sons, Ltd.     

Magnesium chloride supported high mileage catalysts for olefin polymerization. XII. Polymerization of ethylene

Polymerizations of ethylene by the MgCl₂/ethylbenzoate/p-cresol/AlEt₃ TiCl₄-AlEt₃/methyl-p-toluate (CW-catalyst) have been studied. The initially formed active site concentration, [Ti] has a maximum value of 50% of total titanium at 50°C and lower values at other temperatures. The Ti decays rapidly to Ti sites with conc. ca. 10 mol %/mol Ti. The rate constants for four chain transfer processes have been obtained at 50°C: for transfer with AlEt₃, k = 2.1 × 10^?4 s^?1 and k = 4.8 × 10^?4 s^?1; for transfer with monomer, k = 3.6 × 10^?3 (M s)^?1 and K = 8.3 × 10^?3 (M s)^?1; for β-hydride transfer, k = 7.2 × 10^?4 s^?1 and k = 4.9 × 10^?4 s^?1; and transfer with hydrogen, k = 4.0 × 10^?3 torr^1/2 s^? and k = 5.1 × 10^?3 torr^1/2 s^?1. The rate constants for the termination assisted by hydrogen is k = 1.7 (M^1/2 torr^1/2 S)^?1. If monomer is assisting termination as was observed for propylene polymerization, then k = 7.8 (M^3/2 s)^?1. Values of all the rate constants can be higher or lower at other temperatures. Detailed comparisons were made with the results of propylene polymerizations. There are more than four times as many Ti active sites for ethylene polymerization than there are for stereospecific polymerization of propylene; the difference is more than a factor of two for the Ti sites. Certain rate constants are nearly the same for both monomers while others are markedly different. Some of the differences can be explained by stereoelectronic effects.     

Electrocatalytic Oxidation of Acyclovir on Poly(p‐Aminobenzene Sulfonic Acid) Film Modified Glassy Carbon Electrode

Acyclovir is an antiviral effective drug active compound. A glassy carbon electrode (GCE) was modified with an electropolymerized film of p‐aminobenzene sulfonic acid (p‐ABSA) in phosphate buffer solution (PBS). The polymer film‐modified electrode was used to electrochemically detect acyclovir. Polymer film showed excellent electrocatalytic activity for the oxidation of acyclovir. The anodic peak potential value of the acyclovir at the poly(p‐ABSA) modified glassy carbon electrode was 950 mV obtained by DPV. A linear calibration curve for DPV analysis was constructed in the acyclovir concentration range 2×10^?7–9×10^?6 mol L^?1. Limit of detection (LOD) and limit of quantification (LOQ) were obtained as 5.57×10^?8 and 1.85×10^?7 mol L^?1 respectively. The proposed method exhibits good recovery and reproducibility.     

Divergent Melanophore-Dispersing and Tyrosinase-Stimulating Activity of Synthetic Leucine9-α-melanotropin

Leucine⁹-α-melanotropin ([Leu⁹]α-MSH) was synthesized in homogeneous solution by a fragment condensation approach, and it was assayed for its melanophore-dispersing and its tyrosinase-stimulating activity with a reflectometric in vitro frog skin assay and with cultured mouse melanoma cells, respectively. In both assay systems, parallel log dose-response curves were obtained for ([Leu⁹)]α-MSH and α-MSH; however, in the frog skin assay the activity of the title compound was 1 middot; 10¹⁰ Units/mmol, i.e. 25% of the activity of α-MSH, whereas its tyrosinasestimulating potency was only 1% compared to α-MSH (EC₅₀= 2.5 · 10^?7M ). This indicates a major difference in the recognition/stimulation process of the receptors of the two cell types.     

Rate constants for hydrogen abstraction reactions of the sulfate radical,SO4−. Alkanes and ethers

Rate constants have been determined for the reactions of SO₄^? with a series of alkanes and ethers. The SO₄^? radical was produced by the laser-flash photolysis of persulfate, S₂O₈^2?. For methane, only an upper limit of 1 × 10⁶ M^?1 s^?1 could be determined. For ethane, propane, and 2-methylpropane, rate constants of 0.44, 4.0, and 10.5 × 10⁷ M^?1 s^?1 were found. For ethyl and n-propyl ether, rate constants of 1.3 × 10⁸ and 2.2 × 10⁸ M^?1 s^?1 were found and for 1,4-dioxane and tetrahydrofuran, rate constants of 7.2 × 10⁷ and 2.8 × 10⁸ were obtained. The reaction of SO₄^? with allyl alcohol was also studied and found to have a rate constant of 1.4 × 10⁹ M^?1 s^?1.     

QSAR studies of phenylhydrazine-substituted tetronic acid derivatives based on the 1H NMR and 13C NMR chemical shifts

The quantitative structure–activity relationship models of 40 phenylhydrazine-substituted tetronic acid derivatives were established between the ¹H nuclear magnetic resonance (NMR) and ¹³C NMR chemical shifts and the antifungal activity against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis, and Colletotrichum capsici. The models were validated by R, R², R_A², variance inflation factor, F, and P values testing and residual analysis. It was concluded from the models that the ¹³C NMR chemical shifts of C8, C10, C7, and the ¹H NMR chemical shifts of Ha contributed positively to the activity against Fusarium graminearum, Botrytis cinerea, Colletotrichum capsici, and Rhizoctonia cerealis, respectively. The models indicated that decreasing the election cloud density of specific nucleuses in compounds, for example, by the substituting of electron withdrawing groups, would improve the antifungal activity. These models demonstrated the practical application meaning of chemical shifts in the quantitative structure–activity relationship study. Furthermore, a practical guide was provided for further structural optimization of the antifungal phenylhydrazine-substituted tetronic acid derivatives based on the ¹H NMR and ¹³C NMR chemical shifts.     

Studies on some radical transfer reactions by entrapping the radicals as polymer end groups. II. Reactions of ȮH radicals with amino acids

The reaction of ?H radicals with a number of aliphatic amino acids has been studied by entrapping the resultant radicals as end groups of poly(methyl methacrylate) that have been detected and estimated by the sensitive dye partition technique. The rate constants of the reaction (in mol^?1 L S^?1) of 7 amino acids at 25°C and at pH 1.00 have been determined as 8.33 × 10⁸ for glycine, 2.56 × 10⁹ for β-alanine, 2.01 × 10⁹ for β-alanine, 3.99 × 10⁹ for 4-amino butyric acid, 7.56 × 10⁹ for (1+) valine, 1.42 × 10¹⁰ for (1?) leucine, and 5.98 × 10¹⁰ for 6-amino caproic acid. Glycine, α-alanine, β-alanine, and 4-amino butyric acid produced radicals that underwent deamination and incorporated only carboxyl-bearing end groups in the polymer. The other amino acids, leucine, valine, and 6-amino caproic acid, produced at least two types of radicals, radicals that underwent deamination and those that remained intact, and incorporated in the polymer both carboxyl- and amine-bearing end groups but in different amounts. The latter type of radicals were about 29% from 6-amino caproic acid, 23% from leucine, and 18% from valine. The change of pH from 0.80 to 2.72 did not produce any significant change in the end group profile of the polymer obtained, indicating no appreciable change in the rate of the reaction of ?H radicals with the simplest amino acid glycine in the pH range studied.