Misinsertions

Evans, J., Maccabee, M., Hatahet, Z., Courcelle, H., Bockrath, R., Ide, H. and Wallace, S. (1993). Thymine ring saturation and fragmentation products, lesion bypass, misinsertion and implications for mutagenesis. Mut. Res. 299, 147-156. 

Regiodefects are less readily incorporated into crystallites than defect-free chain sequences. In semicrystalline polymers, increasing levels of misinsertion result in reduced crystallinity. This can affect numerous physical properties, resulting in reduced modulus, lower heat distortion temperature, and decreased tensile strength. 

In practice, the monomers comprising a polymer are never arranged in a purely isotactic or syndiotactic fashion. All stereoregular polymers contain some misinsertions. The polymerization catalyst and polymerization conditions control the level of stereoregularity. 

F and B NMR spectroscopy. The rate of propene polymerisation with this system was only three times faster than that of 1-hexene. This slow rate contributes to the high regioselectivity of the polymerisation no 2,1-propene misinsertions were detected. H and NMR spectroscopy also provided information about the chain termination mechanism here this occurred by p-H elimination in a first-order process. Polymer chain-end epimerisation, i.e. chirality inversion at the P-carbon of the polymer chain (Scheme 8.31), proceeded via a zirconium tert-alkyl (rather than tt-allyl) intermediate [96c]. 

The nature of the dormant state was determined by H NMR end-group analysis. Two types of terminal unsaturations were found, vinylidene end groups indicative of (3-H elimination from 1,2-inserted polymeryl chains, and cis-butenyl end groups, arising from 2,1-misinsertions (Scheme 8.33) the latter were dominant (66%). 

NMR analysis of the polymer also detected low levels of stereo-errors due to enchained 2,1-misinsertions (cf Section 8.9), about 1 in 500. The data suggested that 2,1-insertion is slow but is responsible for the accumulation of dormant states carrying Zr-sec-alkyl chains. 

The stereo-regularity of a polymer can be reduced by a variety of defects. For example, regio-errors arise when a 2,1-monomer insertion occurs instead of a 1,2-in-sertion the latter is usually 10 -10 times faster. Misinsertions can lead to chain termination and formation of butenyl end groups, they can be incorporated into... 

Dong, Q., Copeland, W. C., and Wang, T. S. (1993). Mutational studies of human DNA polymerase a Identification of residues critical for deoxynucleotide binding and misinsertion fidelity of DNA synthesis. / Biol. Chem. 268, 24163-24174. 

The misinsertion of thymine opposite to 06-alkylguanine in DNA is likewise attributed to the fact that at physiological pH the N1 site of this modified guanine does not carry a proton [pATa = 2.4 (55)], even though Watson-Crick pairing with protonated C can be realized (59). Alkylation at the N3 position of guanine acidifies the proton at N1 to such an extent that the cytosine base in the... 

This property can be attributed to the additional /i-sidc-chain, present in valine and absent in methionine. This size-augmentation is monitored by the increased bulk of the steric probe TMeTP resulting in significantly lower misinsertion efficiency by the M184V mutant compared with the natural substrate. 

For example, the rates of propylene and 1-butene polymerisation by the rac.-(IndCH2)2ZrCl2—[Al(Me)0]x catalyst increase in the presence of hydrogen roughly by a factor of 10-60 respectively [260]. These polymers were found to be free of misinserted units hydrogenolysis apparently eliminates the slowly inserted 2,1-enchained monomer units and allows the start of a new, fastgrowing polymer chain [scheme (44)] [30],... 

Different zirconocene-based catalysts cause the occurrence of regioirregula-rities in different ratios only 1,3 misinsertions (ca 1%) are found in polypropylene... 

The structure of ligands in metallocene complexes determines activity, stereoselectivity, and molecular weight of 1-alkene polymerizations, by controlling the preferential conformation of the growing polymer chain which in turn controls the stereochemistry of monomer coordination ( enantiomorphic site control ). The difference between this and the chain-end control mechanism mentioned earlier is that stereo errors due to misinsertions can be repaired.101,106... 

The misinsertions are responsible for the low melting points of the polymers produced at high temperatures. Also, the low molecular weights obtained at industrially favored temperatures (60-70 °C) caused the need for catalyst improvement. Since the mid-1980s about a hundred C2-symmetric metallocenes... 

The classical heterogeneously catalyzed propene polymerization as discovered hy Natta is a stereospecific reaction forming a polymer with isotactic microstructure. During the development of single-site polymerization catalysts it was found that C2-symmetric chiral metallocene complexes own the same stereospecificity. An analysis of the polymer microstructure hy means of NMR spectroscopy revealed that misinsertions are mostly corrected in the next insertion step, which suggests stereocontrol (Figure 6) hy the coordination site, as opposed to an inversion of stereospecificity hy control from the previous insertion steps (chain-end control). In addition, it was found that Cs-symmetric metallocene catalysts lead to syndio-tactic polymer since the Cosee-Arlmann chain flip mechanism induces an inversion of the stereospecificity at every insertion step. This type of polymer was inaccessible by classical heterogeneous systems. 

Scheme 29 Insertion sequences leading to the two major types of enchainment defects in propylene polymerization at a Cs-symmetric active center site isomerization (left) and enantioface misinsertion (right).

Faithful transmission of genetic information depends on the correct insertion of bases during replication, proofreading by DNA polymerases and the excision of misinserted bases. In addition to mutations induced by mismatches during replication, chemical agents, heat and UV radiation can damage DNA. Heat can cause... 

The frequency of these misinsertions is quite high, being about 8% in the more isotactic samples. This value results in an average stereoblock length of only about 12 units and explains the low melting point ( 60 °C) and low crystallinity (<20%) observed for this material and its physical properties, which are... 

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