Activation by complex formation

On the other hand, for the first time, we have synthesized a nonnatural ribozyme using an indirect method (96. 97). A pool of RNAs consisting of random sequences was obtained in the presence of 2 -aminocytidine triphosphate instead of CTP. The pool was incubated with an A-methylmesoporphyrin-immobilized gel, and the bound nonnatural RNAs were then collected and amplified by RT-PCR. The selected nonnatural RNA catalyzed the metalation of porphyrin using the same mechanism. In addition, the selected RNA exhibited a peroxidase activity by complex formation with hemin. 

Protein G. This vitamin K-dependent glycoproteia serine protease zymogen is produced ia the Hver. It is an anticoagulant with species specificity (19—21). Proteia C is activated to Proteia by thrombomodulin, a proteia that resides on the surface of endothefial cells, plus thrombin ia the presence of calcium. In its active form, Proteia selectively iaactivates, by proteolytic degradation. Factors V, Va, VIII, and Villa. In this reaction the efficiency of Proteia is enhanced by complex formation with free Proteia S. la additioa, Proteia activates tissue plasminogen activator, which... 

The reaction between Fe(IlI) and Sn(Il) in dilute perchloric acid in the presence of chloride ions is first-order in Fe(lll) concentration . The order is maintained when bromide or iodide is present. The kinetic data seem to point to a fourth-order dependence on chloride ion. A minimum of three Cl ions in the activated complex seems necessary for the reaction to proceed at a measurable rate. Bromide and iodide show third-order dependences. The reaction is retarded by Sn(II) (first-order dependence) due to removal of halide ions from solution by complex formation. Estimates are given for the formation constants of the monochloro and monobromo Sn(II) complexes. In terms of catalytic power 1 > Br > Cl and this is also the order of decreasing ease of oxidation of the halide ion by Fe(IlI). However, the state of complexing of Sn(ll)and Fe(III)is given by Cl > Br > I". Apparently, electrostatic effects are not effective in deciding the rate. For the case of chloride ions, the chief activated complex is likely to have the composition (FeSnC ). The kinetic data cannot resolve the way in which the Cl ions are distributed between Fe(IlI) and Sn(ll). 

With taken into account, that the constants of the reaction rates are determined via the equilibrium constants of the activated reactive complex formation, and the last in part depend on the solvation processes, it was proposed by Koppell and Palm [22] the following equation in order to determine the influence of medium properties on the reaction rates of processes proceeding in it ... 

The nudeophile is activated by the formation of a titanium(IV)-imido complex 19. The next step is a [2 + 2] cydoaddition with one of the jt-bonds of the allene, depending on the regioselectivity leading to either 20 or 22. Compound 20 then delivers 21 by twofold stepwise proto-demetallation and the latter enamine tau-tomerizes to the imine 24 (Scheme 15.3). Compound 22, on the other hand, should provide allylamines 23, but as we shall see, there are no examples of that mode of reaction known so far. 

The very early reported allene (NMe2)2C=C=C(NMe2)2 [12, 13] can also be considered as a push-push allene and the bent structure is activated upon complex formation as shown in Fig. 34. Reaction with [ClAu(PPh3)] and CU exchange by the weakly coordinating anion SbFg results in the formation of 71 in good yields [20,21]. 

To prevent self-digestion, the pancreas releases most proteolytic enzymes into the duodenum in an inactive form as proenzymes (zymogens). Additional protection from the effects of premature activation of pancreatic proteinases is provided by proteinase inhibitors in the pancreatic tissue, which inactivate active enzymes by complex formation (right). 

In this work, we have chosen several systems stabilized through hydrogen bonds. The homopolymer is a polybase, i.e. PEO, PVME or PVP, and the copolymer is polyacrylic acid with various degrees of neutralization a, in which the acrylates are the non active groups. Complex formation is studied by potentiometry (because complexation induces a variation of the solution pH) and by viscometry and polarized luminescence which respectively give information about the macroscopic and local structure of the complex in solution. The influence of parameters such as the degree of neutralization of PAA a, the concentration ratio r - [polybase]/[PAA], the concentration and the molecular weight of polymers is examined. 

The three elements to be treated in this chapter (Fe, Co, Ni) are the sixth, seventh, and eighth members of the first transition series. The first five members (Sc, Ti, V, Cr, Mn) have been treated in previous chapters (Chapters 12, 13, and 14).The ten elements of this first transition series (Sc through Zn) are characterized by electron activity in the 4s-3d levels. All elements in the 3d transition series are metals, and many of their compounds tend to be colored as a result of unpaired electrons. Most of the elements have a strong tendency to form complex ions due to participation of the d electrons in bonding. Unlike the previous three elements (V, Cr, Mn), these three do not show a variety of oxidation states. The higher oxidation states are almost absent in compounds, Fe showing principally the II and III, Co the II and III, and Ni only the II. The III states are less stable than the II states unless they are stabilized by complex formation. The resemblance of these three elements is notable, they being more like each other than they are to the elements below them. 

Chemical modification may also simply be achieved by complex formation with an optically active agent191. For example, the correlation of the configuration of chiral non-racemic phosphate triesters, such as 11 (see p 417)11, with the relative (when compared with ent- ) change in H chemical shift of the methoxy doublet induced by the addition of Eu(hfc)3192 has been used for the assignment of absolute configuration of optically active phosphate triesters (chiral at phosphorus), which were obtained by asymmetric synthesis as indicated. 

Fig. 1.57. Model of the regulation of translation by insulin. Insulin ( and other growth factors) activates the Akt kinase pathway (see ch. 10), whose final result is the phosphorylation of 4E-BPl, a regulatory protein of translation initiation. The 4E-BP1 protein inactivates the initation factor eIF-4E by complex formation. eIE-4E is required, together with the proteins eIE-4A and p220, for the binding of the 40S subunit of the ribosome to the cap structure of the mRNA. If the 4E-BP1 protein becomes phosphorylated as a result of insulin-mediated activation of the PI3 kinase/Akt kinase cascade, then eIE-4E is liberated from the inactive eIP-4E 4E-BPl complex and protein biosynthesis can begin.

Much work has been done to develop catalyst systems that optimize yield and reduce side reactions. The reaction has an induction period, which depends on the temperature and the amount of catalyst.8 An early patent from Bayer claims that a nearly quantitative yield can be achieved in the conversion of l,2-dibromo-1-chloro-l.2.2-trifluoroethane(5) into 1,1-di-bromo-l-chloro-2,2.2-trifluoroethane (6) when aluminum tribromide is used in 2-broino-2-chloro-1,1,1-trifluoroethane (4) as solvent.12 A Japanese patent26 describes the activation of aluminum trichloride or alumina by pretreatinent with l,L2-trichloro-l,2,2-trifluoroethane (1) (see discussion of compound 19, vide infra). A later patent claims that aluminum trichloride and tribromide can also be activated by complexing with 1,1-dichloro- (CF3CFC12) and 1,1-dibromo-1,2,2,2-tetrafluoroethane (CF3CFBr2), respectively 2 an example of the latter is shown in the formation of bromofluoroalkane 10. 

The key function of sodium is its role in assisting the absorption of glucose and water from the small intestine, both by complex formation (Schultz and Crnran, 1970) and by a phenomenon known as solution drag (Fordtran, 1975). Sodium also aids post-activity recovery by ... 

Formation of aminoacyl-tRNA. This is a two-step process involving a single enzyme that links a specific amino acid to a specific tRNA molecule. In the first step (1) the amino acid is activated by the formation of an aminoacyl-AMP complex. This complex then reacts with a tRNA molecule to form an aminoacyl-tRNA complex (2). 

Thus, CPT is activated 50-fold by complex formation with S02, and hence the complex is the reactive species even though it is very dilute. These results are comparable with previous studies on vinyl ether-maleic anhydride system (14). 

Suzuki et al. examined the effect of various divalent cations on purified recombinant human GCH expressed in Escherichia coli to clarify the molecular mechanism of action of divalent cations on the GCH enzymatic activity [150]. They demonstrated that GCH utilizes metal-free GTP as the substrate for the enzyme reaction. Inhibition of the GCH activity by divalent cations such as Mg(II) and Zn(II) was due to a reduction in the concentration of metal-free GTP substrate by complex formation. Many nucleotidehydrolyzing enzymes such as G proteins and kinases recognize Mg-GTP or Mg-ATP complex as their substrate. In contrast with these enzymes, Suzuki et al. demonstrated that GCH activity is dependent on the concentration of Mg-free GTP [150]. 

Although chlorobenzene is rather inactive in usual reactions, its activity is enhanced by complex formation, and two products are formed by the reaction of stabilized carbanions on the complexed chlorobenzene 207, depending on the conditions [44], The anion of a-methy l propionitrile reacts at the meta position at —78 °C, and the mete-substituted product 208 is obtained by oxidation with I2. However, equilibration (rearrangement) of the carbanion occurs at 25 °C, because the attack of the carbanion is reversible, and the substitution product 209 of the chlorine is obtained. The fluorobenene 210, coordinated by Cr(CO)3, is very reactive. Reaction of y-butyrolactone to the o-lithiated fluorobenzene 211 gives rise to the alkoxide 212, which displaces the fluoride intramolecularly to give the cyclic ether 213 [52], In other words, the complex 211 can be regarded as the 1,2-dipolar synthon 214. However, Cr(CO)3-complexed aromatic bromide and iodide can not be used for the nucleophilic substitution. 

The enantioselective complexation technique can also be applied as one step in the reaction sequence, providing chiral substrates for the next step. We will now discuss the example of Gabriel synthesis between potassium phthalimide 41 and alkyl bromide 42, which leads to optically active amines (Scheme 1) [51], Instead of the complicated preparation of chiral alkyl bromides (halides), imides (43), which are reaction intermediates, have been resolved. Upon treatment with hydrazine and KOH, these gave optically active amines. The chiral host (S,S)-(-)-6 or the chiral biaryl host (,S>(-j-40 was used for the effective resolution of the intermediates 43. Racemic mixtures 43a-d were resolved by complex formation with the host (S,S)-(-)-6 in a mixture of diethyl ether and light petroleum. 

Toda, F., Tanaka, K., and Kido, M. (1988) Optical Resolution of 2-Methylpiperazine by Complex Formation with Optically Active l-Phenyl-l-(o-chlorophenyl)- prop-2-yn-l-ol and... 

The carboxyl group seems to activate epoxides slightly toward nucleophilic attack by amines, and in the absence of catalysts most 2,3-epoxycarboxylic acids react with amines to yield 2-amino-3-hydroxycarboxylic acids [346-348], This regioselectivity can, however, be overridden by complex formation with Ti(OiPr)4 (Scheme4.77). 

After neutralization with ethylenediamine at pH 6.6, the active centre is riot dissociated, and ethylenediamine adds one proton. The increase in polymerization rate is caused by complex formation between these two molecules. The transition complex can be represented schematically as... 

The ability of compound to be hydrolyzed depends on the cation parameters I and % which govern the polarizability of Me - O bond and the formation of strong hybrid orbitals. For d-elements, d-, s- and p-orbitals in the outer electron shells are close to each other by energy. Therefore, d-elements exhibit an increased trend to hybridization with the participation of d-orbitals. This fact, as well as large I and X values, help to form stable complex compounds, while the ability to hydrolysis is closely correlated with the activity to complex formation. 

Notably, when the same cyclisation was carried out using sodium cobalt(I)salophen, the reaction became selective for toddaquinoline methyl ether <00TL6681>. This apparent diehotomy was attributed to the formation of a Lewis acid - Lewis base complex between cobalt(II)salophen and the pyridine moiety. Loss of bromide from the radical anion 151 generates aryl radieal 152 which adds to the proximal pyridine giving 153. Dehydrocobaltation to toddaquinoline methyl ether 149 completes the sequence (Scheme 42). Notably, as the pyridine ring is activated by complexation to the Lewis acidic Co(II), the eyelisation is more akin to a Minisci reaction. Consequently, cyclisation to C6 is promoted in this case <01T4447>. 

Figure 1 Partial representation of a signal transduction network, mediated by a cell surface receptor. The molecules are organized hierarchically (roughly, from top to bottom) according to their functions as adaptors, receptor-recruited enzymes, membrane-associated substrates, and effector kinases. Arrows represent activation mechanisms, whether by complex formation or covalent modification V bars indicate negative regulation.

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