Molekülstruktur in der Theorie der Spinvalenz I

Zusammenfassung Wie in der Theorie der Valenzstrukturen (Kimball 1940), so kann man auch in der Theorie der Spinvalenz ohne Rechnung, d. h. nur mit den Mitteln der Gruppen- und Darstellungstheorie, zu Aussagen über die Molekülstruktur von Verbindungen des Typs ML _n kommen. Die Ergebnisse für sog. ¹ A ₁-Moleküle werden angegeben und mit denen von Kimball verglichen.

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Spin valence theory provides a basis for the group theoretical derivation of the structure of ML _n -molecules. Results for molecules in a totally symmetrical ground state are compared with predictions of the valence bond method (Kimball 1940).

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Résumé La théorie de la valence de spin permet de dériver les structures de molécules du type ML _n á l'aide de la théorie des groupes. Des résultats pour de molécules en état ¹ A ₁ (totalement symétrique) sont comparés á ceux de la méthode de mésomérie (Kimball 1940).

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Auszugsweise vorgetragen auf der Westdeutschen Chemiedozententagung, Freiburg i. Brsg., 27.–30. 4. 1964 und der 8. I. C. C. C., Wien, 7.–11. 9. 1964.     

Die durch Silberionen katalysierte Umlagerung von Propargyl-phenyläther

It is known that propargyl-phenylethers rearrange at about 200° to 2 H-chromenes [1–4]. It is shown that this rearrangement occurs in benzene or chloroform at lower temperatures (20–80°) in the presence of silver-tetrafluoroborate (or-trifluoracetate). The ethers examined are presented in Scheme 1. Thus in chloroform at 61° in the presence of AgBF₄, phenyl-propargylether ( 3 ) yields 2 H-chromene ( 13 ). With 0.78 molar equivalents AgBF₄ in benzene at 80° the same ether 3 yields a 3:1 mixture of 2-methyl-cumaron ( 14 ) and 2 H-chromene ( 13 ). From 1′-methylpropargyl-phenylether ( 4 ) and 2′-butinyl-3,5-dimethylphenylether ( 5 ) under similar conditions the corresponding chromenes 16 and 17 resp. are obtained. Rearrangement of propargyl- and 2′-butinyl-1-methyl-2-naphthylether ( 6 and 7 resp.) in benzene at 80° in the presence of AgBF₄ gives the corresponding allenyl-naphthalenones 18 and 19 resp. Treatment of propargyl- and 2′-butinyl-mesityl-ether ( 8 and 9 resp.), and propargyl- and l′-methylpropargyl- 2 , 6 -dimethyl-phenylether ( 10 and 11 resp.) in benzene at 80° with AgRF, yields as the only product the corresponding 3 -allenyl-phenols 21 , 22 , 24 and 25 (Scheme 3). It is shown that in the presence of μ-dichlor-dirhodiuni (1)-tetracarbonyl in benzene a t 80° the ether 4 rearranges to 2-methyl-2H-chromene (16). However with this catalyst the predominant reaction is a cleavage to phenol. No reaction was observed when ethers 3 and 12 , (Scheme 7 ) were treated with the tris-(trimethylsily1)-ester of vanadic acid in benzene a t 80° (see also [8]). By analogy with the known mechanism for thc silver catalysis of the reversible propargylesterl/allenylester rearrangement [S], the silver (1)ion is assumed to form a pre-equilibrium π-complex with the C, C-triplebond of the substrate. This complex then undergoes a [3s, 3s]-sigmatropic rearrangement (Scheme 2). In the case of the others 6 , 7 and 12 the resulting allenyldienones were isolated. The 2,G-dimethyl substituted ethers 8 , 9 , 10 and 11 resp. first give the usual allenyl- dienones (Scheme 3). These then undergo a novel silver catalysed dienon-phenol-rearrangement (Sclzenzu4) to give the 3-allenylphenols 21 , 22 , 24 and 25 . Thc others 3 , 4 and 5 with free ortho positions presumably rearrange first to the non-isolated 2-allenyl-phenols 15 , 42 and 43 resp.(Scheme 7). These then rearrange, either thermally or by silver (1)ion catalysis to the 2H-chromenes 13 , 16 and 17 resp. The rate of the rearrangement of 2-allenylphenol ( 15 ) to 13 at room temperature in benzene or chloroform is approximately doubled when silver ions are present as catalyst.     

New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven-membered ring

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde ( 1 ) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde ( 2 ) as well as dihydrolactaroviolin ( 3 ) yielded with 4a the corresponding styrylazulenes 6 and 7 , respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9 , respectively (cf. Scheme 1). The reaction of 4,6,8-trimethylazulene ( 10 ) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b . 4,6,8-Trimethylazulene-2-carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH₄) and dehydrogenation (MnO₂) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b , respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene ( 21 ) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me₂N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4-NO₂C₆H₄CH=NC₆H₅ ( 22e ) in DMF yielded no corresponding styrylazulene derivative 23e . Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene ( 27 ) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene ( 10 ) and benzanil ( 22a ) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).     

分光光度法测定脱氧核糖核酸——基于其与亚甲蓝的反应

试验发现在pH 6.5的B-R缓冲溶液中在加脱氧核糖核酸(DNA)后亚甲蓝溶液在其吸收峰666 nm波长处的吸收明显减弱(即色泽减褪),而且吸光度的减弱(ΔA)程度与DNA的质量浓度在10.0 mg.L-1以内保持线性关系,其相关系数为0.9998,此反应对DNA的检出限为0.10 mg.L-1,分别以蛋白酶、胰蛋白酶及溶菌酶作为基体定量加入DNA配制成3种合成样品,按所提出方法进行分析,测得回收率结果在98.4%~101.0%之间,分析结果的RSD(n=11)值在1.1%~3.1%之间。对反应条件(包括亚甲蓝的浓度、反应的温度、酸度及时间等因素)作了试验和选定,还对反应机理作了简要的讨论。     

Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells

Enterovirus 71 (EV71) is a dominant pathogenic agent that may cause severe central nervous system (CNS) diseases among infants and young children in the Asia-pacific. The inflammasome is closely implicated in EV71-induced CNS injuries through a series of signaling pathways. However, the activation pathway of NLRP3 inflammasome involved in EV71-mediated CNS injuries remains poorly defined. In the studies, EV71 infection, ERK1/2 phosphorylation, and activation of NLRP3 are abolished in glioblastoma cells with low vimentin expression by CRISPR/Cas9-mediated knockdown. PD098059, an inhibitor of p-ERK, remarkably blocks the vimentin-mediated ERK1/2 phosphorylation in EV71-infected cells. Nuclear translocation of NF-κB p65 is dependent on p-ERK in a time-dependent manner. Moreover, NLRP3 activation and caspase-1 production are limited in EV71-infected cells upon the caffeic acid phenethyl ester (CAPE) administration, an inhibitor of NF-κB, which contributes to the inflammasome regulation. In conclusion, these results suggest that EV71-mediated NLRP3 inflammasome could be activated via the VIM-ERK-NF-κB pathway, and the treatment of the dephosphorylation of ERK and NF-κB inhibitors is beneficial to host defense in EV71-infected CNS.     

Lipases,liposomes and lipid-prodrugs

Colloidal and interfacial phenomena lie at the core of drug formulation, drug delivery, as well as drug binding and action at diseased sites, e.g., in cancer therapy. We review a class of liposome-based drug-delivery systems whose design and functional properties are intimately controlled by the stability of sub-micron structures, lipid-bilayer interfaces, and interfacially activated enzymes that can be exploited to target and deliver drugs. Moreover these drugs can themselves be special lipid molecules in the form of lipid prodrugs that both form the liposomal carrier as well as the substrate for endogenously upregulated lipases that turn the prodrugs into potent drugs precisely at the diseased site.     

Effect of infiltration material on a LSM15/CGO10 electrochemical reactor in the electrochemical oxidation of propene

The effect of infiltrating on a La_0.85Sr_0.15MnO₃/Ce_0.9Gd_0.1O_1.95 11-layer electrochemical reactor with CeO₂ and Ce_0.8Pr_0.2O_2?δ was studied in propene oxidation at open-circuit voltage and under polarization as a function of reaction temperature. This work outlined the importance of catalytic and electrochemical properties of infiltrated material on the ability to increase propene conversion under polarization with good faradaic efficiency. Electrochemical impedance spectroscopy was used to study the effect of infiltration material on electrode properties. The infiltration of a mixed ionic and electronic conductor, like Ce_0.8Pr_0.2O_2?δ , increased the electrode performance at low temperature but decreased the lifetime of the oxygen ion promoters on the catalyst/electrode surface, reducing the faradaic efficiency of the reaction. The infiltration of CeO₂ provided high propene conversion at open circuit and high effect of polarization associated with good faradaic efficiency, especially at low temperature.     

Synthesis and characterization of new selective Zn fluorescent probes for functionalization: in vitro Cell imaging applications

Herein the synthesis and characterization of new, lipophilic highly Zn²⁺-selective fluorescent probes are reported. High affinity for zinc (K_d 1.1–8.0 nM) over other biologically relevant metals and mixtures of metals was observed. Excitation at 360 nm afforded an emission spectrum with maximum at 530 nm for the zinc bound complex. The linear relationship between fluorescence intensity and zinc concentration indicates that FZnA-probes can be used for quantification. The probes have been synthesized in 28–45% overall yield and the feasibility for further functionalization with biologically relevant side chains has been demonstrated. In vitro studies using PC12 cells and 10 μM of one of the novel probes (FZnA-Ada) visualized endogenous labile Zn²⁺ after 45 min incubation time.     

1,1′,1′′-(2,4,6-Trihydroxybenzene-1,3,5-triyl)triethanone tautomerism revisited

It has recently been suggested that 1,1′,1′′-(2,4,6-trihydroxybenzene-1,3,5-triyl)triethanone may be tautomeric. Using ¹³C NMR chemical shifts and deuterium isotope effects on ¹³C chemical shifts, it is demonstrated that this is not the case. This compound occurs as a strongly hydrogen bonded benzene structure with hydrogen bonds between OH groups and the acetyl groups in both non-polar and hydrogen donating solvents. Quantum-chemical calculations using MP2 and M06-2X methods show substantial preference for the phenol structure in both the gas phase, and in cyclohexane and methanol. In addition, conventional UV–vis spectroscopy data suggest not tautomeric, but aggregation behaviour of the molecule in methanol and acetonitrile.     

Rational Tuning of the Reactivity of Three-Membered Heterocycle Ring Openings via SN2 Reactions

The development of small-molecule covalent inhibitors and probes continuously pushes the rapidly evolving field of chemical biology forward. A key element in these molecular tool compounds is the “electrophilic trap” that allows a covalent linkage with the target enzyme. The reactivity of this entity needs to be well balanced to effectively trap the desired enzyme, while not being attacked by off-target nucleophiles. Here we investigate the intrinsic reactivity of substrates containing a class of widely used electrophilic traps, the three-membered heterocycles with a nitrogen (aziridine), phosphorus (phosphirane), oxygen (epoxide) or sulfur atom (thiirane) as heteroatom. Using quantum chemical approaches, we studied the conformational flexibility and nucleophilic ring opening of a series of model substrates, in which these electrophilic traps are mounted on a cyclohexene scaffold (C₆H₁₀Y with Y=NH, PH, O, S). It was revealed that the activation energy of the ring opening does not necessarily follow the trend that is expected from C−Y leaving-group bond strength, but steeply decreases from Y=NH, to PH, to O, to S. We illustrate that the HOMO_Nu–LUMO_Substrate interaction is an all-important factor for the observed reactivity. In addition, we show that the activation energy of aziridines and phosphiranes can be tuned far below that of the corresponding epoxides and thiiranes by the addition of proper electron-withdrawing ring substituents. Our results provide mechanistic insights to rationally tune the reactivity of this class of popular electrophilic traps and can guide the experimental design of covalent inhibitors and probes for enzymatic activity.