Open complexes

This complex is formed with more than 1.0 equivalents of (C2H5)2A1C1 with concomitant formation of Li2AICI2. The open and chelated structures have been characterized by NMR.90 The chelated structure is substantially more reactive than the open complex, which accounts for the increase in enantioselectivity with more than 1.0 equivalents of catalyst. 

Electronic factors also influenced the outcomes of these cyclization reactions cyclization of pyrrole 84 to bicyclic amine 85 is catalyzed by the sterically open complex 79a. In this reaction, initial insertion into the Y - H bond occurred in a Markovnikov fashion at the more hindered olefin (Scheme 19) [48]. The authors proposed that the Lewis basic aromatic ring stabilizes the electrophilic catalyst during the hydrometallation step, overriding steric factors. In the case of pyrroles and indenes, the less Lewis basic nitrogen contained in the aromatic systems allowed for the cyclization of 1,1-disubstituted alkenes. 

The mesoionic tetrazole dehydrodithizone is transformed by iron penta-carbonyl into 4-phenyl-2-phenylazo-A2-l,3,4-thiadiazolin-5-one, presumably by a mechanism of ring opening, complexation, carbonyl insertion and subsequent ring closure (Scheme 128).193 Unfortunately, analogous processes do not occur on other mesoionic compounds in the 1,2,3-oxadiazole, s-triazole or tetrazole series, and the scope of this unusual carbonylation is probably limited. 

Enzyme-stabilized single-stranded DNA (known as the open complex) is the first intermediate formed in transcription initiation of RNA polymerases its formation is the rate-limiting step. Designing molecules which bind specifically to the open complex is a strategy for generating potent transcription inhibitors. The redox-stable complex of Cu(I) with 1,2-dimethyl- 1,10-phenanthroline is an example of such a strategy (405). The Cu(I) complex binds specifically to the single-stranded DNA of transcriptional open complexes and is an effective inhibitor of eukaryotic and prokaryotic transcription. 

Scheme III shows Liberman s associative ring closure mechanism 19). The participation of surface hydrogen atoms (26) in the cyclization-ring-opening complex is noteworthy. The other atoms of the C5 ring are claimed as lying on the metal linked to it by physisorption forces.

The central feature of the mechanism is the 3-cuprio(III) enolate Cpop, of an open, dimeric nature, as shown by comparison of theory with experimentation involving NMR and KIEs [80, 81]. This species serves as the direct precursor to the product (Scheme 10.5, top box). In this critical CPop complex, copper/olefin (soft/soft) and a lithium/carbonyl (hard/hard) interactions are present. The open complex may be formed directly, by way of an open cluster (bottom left of Scheme 10.5), or by complexation of a closed cluster with the enone (CPcl). Experiments have shown that the enone/lithium complex (top left of Scheme 10.11) is a deadend species [60, 74]. 

Fig. 10.6. 3D structure of the open complex between acrolein and Me(ethynyl)CuLI LiCI, with Me20 coordinated to each lithium atom (B3LYP/631 A). Bond lengths are in angstroms. 

Fig. 1.27. Two-step mechanism of transcription initiation. The binding of a procaryotic RNA polymerase to its promoter can be subdivided into two steps. In the first step the RNA polymerase binds to the closed promoter with low affinity. The closed complex isomerizes in a second step to an open complex in which the promoter is partially unwound. Detailed consideration reveals that further steps can be distinguished. These are not shown here for simplicity reasons.

This type of promoter displays markedly different characteristics compared to the o -dependent promoter. The o -contammg holoenzyme binds tightly to the promoter in the absence of transcriptional activators. In this closed state, however, it is not capable of initiating transcription. The transcriptional activators are required in this case to activate the promoter-bound holoenzyme for initiation, i.e. to transform it into the open complex (see Fig. 1.29). Activation is mediated via protein-protein interactions between the transcriptional activator and the RNA polymerase holoenzyme, and is accompanied by ATP hydrolysis. The binding site for the transcriptional activator is found at a distance of ca.llO bp upstream form the start site and can be shifted further upstream without loss of stimulatory effect. Direct interaction of the holoenzyme with the bound transcriptional activator is possible due to loop formation of the intervening DNA. The strict dependency on transcriptional activators for transcription initiation indicates that the DNA-bound holoenzyme alone is not capable of isomerizing to the transcription-competent open complex. The transition to the open complex requires interactions with the transcriptional activator, an event which occurs with ATP hydrolysis. 

Fig. 1.29. Mechanism of promoter activation of (/ -dependent genes in procaryotes. The formation of an open, initiation-competent transcription complex for (/ -dependent genes requires the assistance of transcription activators, which bind to their cognate UAS element. Upon loop formation of the intervening DNA sequences, the transcription activator interacts with the (/ -con-taing RNA polymerase bound to the promoter. The activation is accompanied by ATP hydrolysis and leads to the formation of an open complex.

Wu and Brodbelt have studied the gas-phase fragmentation reactions of HOMg(L) complexes of crown ethers and glymes . A common loss involves units of C2H4O, which can either directly occur from the precursor ion, or can be triggered by an initial interligand reaction between HO and L. This latter reaction is illustrated in Scheme 11 for the complex of 12-Crown-4. Thus loss of H2O from the initial adduct 56 yields the ring-opened complex 57, which contains a coordinated alkoxide moiety, which can then lose an epoxide to form the related complex 58. 

The pathway of transcription initiation is becoming much better defined (Fig. 26-6a). It consists of two major parts, binding and initiation, each with multiple steps. First, the polymerase binds to the promoter, forming, in succession, a closed complex (in which the bound DNA is intact) and an open complex (in which the bound DNA is intact and partially unwound near the... 

A satisfactory mathematical model for initiation of transcription supposes that the polymerase and DNA bind reversibly to form a complex with formation constant Kf. This initial specific polymerase-promoter complex is referred to as a closed complex because it is thought that the bases in the DNA chain are all still paired. It is postulated that in a rate-determining step the closed complex is converted into an open complex, which is ready to initiate mRNA synthesis (Eq. 28-1).26 67 In the open complex the hydrogen bonds... 

It is clear from Eq. 28-1 that the efficiency of initiation depends upon both the affinity Kt and the rate constant k for opening of the double helix. Notice that the Pribnow sequence is AT-rich therefore, opening of the helix at this point would be easier than in a GC-rich region. Tlius, the Pribnow sequence may represent a point of entry of RNA polymerase to form the open complex.67 Other upstream A T tracts are often present frequently at about the -43 position in the UP element. They also seem to strengthen promoter activity.68 Tire open complex is thought to undergo some kind of isomerization to form an initial transcribing... 

Fig. 12. The 2D [1H,15N] HSQC-NMR spectrum of the HPLC-isolated dien ring-opened complex at pH 4.0. Only the NH2 group of L-MetH was 15N-labelled, and the four sets of crosspeaks (peaks a, a to d, d ) can be assigned to the non-equivalent Pt-NH2 groups in the four diastereomers of [Pt(dienH-A,AO(15N-L-Met-YA012+- All peaks have 2J(NHa, NHb) of ca. 12 Hz, while only peaks a and b have an additional V( a-CH.NHj of ca. 13 Hz. (Adapted...

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