Minor Hoechst

Propane, 1-propanol, and heavy ends (the last are made by aldol condensation) are minor by-products of the hydroformylation step. A number of transition-metal carbonyls (qv), eg, Co, Fe, Ni, Rh, and Ir, have been used to cataly2e the oxo reaction, but cobalt and rhodium are the only economically practical choices. In the United States, Texas Eastman, Union Carbide, and Hoechst Celanese make 1-propanol by oxo technology (11). Texas Eastman, which had used conventional cobalt oxo technology with an HCo(CO)4 catalyst, switched to a phosphine-modified Rh catalyst ia 1989 (11) (see Oxo process). In Europe, 1-propanol is made by Hoechst AG and BASE AG (12). 

The cause of the explosion, which also left four people seriously injured and 31 others with minor injuries, is unknown. A Hoechst Celanese spokesman says that the first blast occurred near a gas-fired boiler and the second blast at a nearby reactor in which butane is reacted with steam to produce acetic acid. The 35-year-old plant employs 600 persons, 150 as contract maintenance and construction workers, but the blasts on Saturday only involved a weekend crew of 60. 

Hoechst 33342 [2 -(4-ethoxyphenyl)-5-(4-methyl-l-piperazinyl)-2,5 -bi-IH-benzimidazole Ho342 I], a bisbenzimidazole dye, binds to adenine/thymine-rich regions in the minor groove of DNA. This dye induces apoptosis and inhibits topo 1 activity in vivo. It has been suggested that the destruction of immunoreactive topo I and topo I-DNA complexes or cleavable complexes results in inhibition of topo I activity, a key step in the Hoechst 33342-induced apoptotic process [40]. 

It was thought that in order to investigate further the binding of the Hoechst agent to DNA, one must determine its optimum geometry by theoretical calculations and dock the molecule into the minor groove.60... 

Bisbenzimidazoles (for a review, see Martin 1998) protect cells against ionizing radiation (Denison et al. 1992 Lyubimova et al. 2001). Bisbenzimidazoles such as Hoechst 33258 strongly bind to the minor groove of B DNA (Pjura et al. 1987 in a dodecamer the ATTC region is the preferred intercalating site). 

Other commonly used dyes include Hoechst 33258 and DAPI (4/,6-diamidino-2-phenylindole), both of which show selectivity towards poly A-T sequences. This selectivity limits the utility of these dyes as generic transducers in sensor applications. These dyes associate with double-stranded nucleic acids in a groove-binding motif, more specifically, via binding in the minor groove of B-DNA [41]. 

L. J., Clark, G.R., Martin, R.F., White, J. Structures of m-iodo Hoechst-DNA complexes in crystals with reduced solvent content implications for minor groove binder dmg design. Nucleic Acids Res. 2000, 28, 1252-1258 (b) 1QV8, 1QV4 Martin, R. F., Broadhurst, S., Reum,... 

Hoechst 33258 binds to the minor groove of double-stranded DNA with a preference for the A-T sequence (Pjura et al. 1987). Interaction between DNA and proteins very often induces structural modifications in both interacting molecules. Such modifications in DNA can be characterized with 2-aminopurine (2AP), which is a highly fluorescent isomer of adenine. 2AP does not alter the DNA structure. It forms a base pair with thymine and can be selectively excited, since its absorption is red-shifted compared to that of nucleic acids and aromatic amino acids. In addition, its fluorescence is sensitive to the conformational change that occurs within the DNA (Rachofsky et al. 2001). 

The fluorescence lifetimes of the four natural DNA bases within the femtosecond range are too short to be useful as spectroscopic probes to characterize the solvation dynamics of DNA (31). The minor groove binder Hoechst 33258, the fluorescent adenine analog 2-Aminopurine (2Ap), and the base pair mimic coumarine 102-abasic site are better probes because they exhibit longer lifetimes and better solvatochromic properties. Of the two base pair analogs, the coumarine 102-abasic site base pair mimic disrupts the native DNA structure more than the adenine analog 2Ap. However, the spectroscopic characteristics of the former are superior to those of 2Ap for probing solvation dynamics. 

Models of the interaction of Hoechst 33258 with the oligonucleotides studied were generated based on the intermolecular NOEs. The models of the 1 1 complexes indicated that the ligand interacted with the four AT base pairs located at the center of the sequence. Interestingly, there was no evidence for interactions with GC base pairs on the periphery of the binding sites. In the 2 1 complex reported by Searle and Embrey (92), the array of contacts observed located the ligand in the minor groove at the center of the 5 -TTTT-3 and 5-AAAA-3 sites, as illustrated in Fig. 12.24. 

Back in 1974, Celanese (later Hoechst Celanese) started the production of bu-tanals by a process [192] which closely resembles the LPO one subsequently (1976) established by UCC. It is an open question which of the two companies was the really first to introduce low-pressure hydroformylation, as UCC claims to have run an ethylene hydroformylation unit at Ponce before the start-up of the propene unit at the same site [222]. There are only minor differences if any, between the Celanese and the UCC process [192]. 

Only a small minority of organometallic reactions have cleared the hurdle to become catalytic reality in other words, catalyst reactivation under process conditions is a relatively rare case. As a matter of fact, the famous Wacker/Hoechst ethylene oxidation achieved verification as an industrial process only because the problem of palladium reactivation, Pd° Pd", could be solved (cf. Section 2.4.1). Academic research has payed relatively little attention to this pivotal aspect of catalysis. However, a number of useful metal-mediated reactions wind up in thermodynamically stable bonding situations which are difficult to reactivate. Examples are the early transition metals when they extrude oxygen from ketones to form C-C-coupled products and stable metal oxides cf. the McMurry (Ti) and the Kagan (Sm) coupling reactions. Only co-reactants of similar oxophilicity (and price ) are suitable to establish catalytic cycles (cf. Section 3.2.12). In difficult cases, electrochemical procedures should receive more attention because expensive chemicals could thus be avoided. Without going into details here, it is the basic, often inorganic, chemistry of a catalytic metal, its redox and coordination chemistry, that warrant detailed study to help achieve catalytic versions. 

Hoechst 33258 binds to the minor groove of DNA. When 365 nm light (long UV) excites this dye, fluorescence results and can be measured by mini-fluorometer (as described here), fluorescence spectrophotometer (14) or fluorescence microtiter plate-reader. We have also used a microtiter (96-well) based assay 10 pL sample or standard (range 0-50 pg/mL DNA) and 100 pL Hoechst (1 pg/mL) per well. 

Bisbenzimidazole derivatives such as Hoechst 33258 (also known as Pibenz-imol) 28 (Fig. 2) is a A/T base pair selective compound that binds in the minor groove of DNA [37]. To investigate its full potential, a number of benzimidazole Hoechst motifs have been synthesized and evaluated for various biological activities [38-40]. 

Fig. 18.11. Chemical formulae of minor groove binding drugs a Netropsin, b distamycin, c Hoechst 33258, and d berenil...

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