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Happy Birthday to Bernd Giese

2020; Wiley; Volume: 362; Issue: 11 Linguagem: Inglês

10.1002/adsc.202000065

1615-4169

Armido Studer, Dennis P. Curran,

Radical Photochemical Reactions

It was planned to celebrate the 80th birthday of Prof. Bernd Giese this June within the frame of the International Symposium on Organic Free Radicals (ISOFR-13). Due to the Corona pandemic, the ISOFR-13 had to be postponed and is now scheduled to take place in Münster (Germany) from May 24th to May 28th in 2021. A mini-symposium within the ISOFR-13 that was scheduled in honor of Prof. Giese, a pioneer and hero in free radical chemistry, had to be cancelled as well. However, the current special issue of Advanced Synthesis & Catalysis originally planned to appear during the ISOFR has remained on track and is dedicated to this highly influential scientist. In the following, we will briefly summarize his outstanding lifetime contributions to the fields of organic and biological radical chemistry. Trained in classical physical organic chemistry, Prof. Bernd Giese now defines a modern physical organic chemist, moving his tools of the trade freely between areas as diverse as organic synthesis and nucleic acid biochemistry. Prof. Giese has made fundamental contributions to the understanding of chemical and biochemical reactions and to the development and the use of synthetic methods. In the areas below, his work is widely viewed as original, creative, pioneering, in short, seminal. 1) The Isoselective Relationship: By studying halogen abstraction reactions of radicals as well as cycloaddition reactions of carbenes, Prof. Giese discovered that the selectivity order of these reactive intermediates could be inverted by changing the reaction temperature. This inversion is caused by entropy effects because when bimolecular reactions have early transition states, a substrate variation can have a large effect on the activation entropy. Depending upon the temperature, the free energy difference (selectivity) is either dominated by enthalpy or entropy effects. Giese explained this behavior by an isoselective relationship, which is an extension of the isokinetic relationship. The relationship is now routinely used as a mechanistic tool. 2) C,C-Bond Forming Synthesis via Radicals: Using alkylmercury and alkyltin hydrides, Prof. Giese prevented the radical polymerization of alkenes after the first C,C-bond forming step. This led to a new synthetic method, now commonly called the Giese reaction, whose basic rules of reactivity and selectivity were delineated primarily by Giese. This synthetic method is widely used today, and Giese himself pioneered its use especially in the area of carbohydrates. Typically, physical organic studies are undertaken to explain synthetic observations. The Giese reaction is a rare and dramatic example in which the fundamental physical organic chemistry studies both enabled and inspired the subsequent synthesis work. 3) Mechanism of the Radical Additions to Alkenes: The addition of carbon centered radicals to alkenes is the decisive step in radical polymerizations and in the Giese reaction. Using competition kinetic experiments, steric and polar effects were quantitatively explored and the reaction mechanism was elucidated. The validity of this mechanism was demonstrated by time-resolved kinetic experiments (H. Fischer) as well as quantum chemical calculations. This mechanism is now arguably one of the most well understood mechanisms in organic chemistry, and the synthetic utility and predictability of radical addition reactions derives directly from this understanding. 4) Stereochemistry of Radical Reactions: The guidelines for the stereochemistry of radical reactions were worked out by ESR spectroscopic studies, chemical trapping experiments, and quantum chemical calculations. Giese, together with Ned Porter and one of us (DPC), demonstrated that the rules for the stereochemistry of closed shell systems could also be applied to open shell systems. Giese also discovered a spectacular memory effect of chirality in Norrish–Yang photocyclizations and attributed the effect to intermediate singlet biradicals. 5) Radicals in Biological Systems: Faced with the growing importance of radicals in biological systems, Giese's group has generated many bioorganic radicals and studied their reactions by kinetic measurements and product analysis. This has led to proposals of new mechanisms of the radical-induced DNA and lipid cleavages, and to a deeper understanding of the enzyme ribonucleotide reductase. 6) Electron Transfer through DNA and Peptides: Under the conditions of oxidative stress, DNA bases, especially guanine, become oxidized. Giese worked out a method for site-selective oxidations of guanines and studied the question of whether and how electrons can migrate through DNA. To explain the experimental results, Giese suggested a hopping mechanism for long distance charge transfer through DNA. This mechanism explains why long distance charge transport through DNA is possible even though each hopping step is strongly distance dependent. In a landmark 2001 Nature paper, Giese reported that also endothermic hole transfer from guanine to adenine can occur if the distance for the exothermic step is very long. This explains the nearly distance independent hole transport over long adenine:thymine sequences. In 2003, he developed a new molecular system for site-selective electron injection into thymine of DNA strands. Breath-taking experiments with this assay demonstrate that a single electron repairs more than one UV induced lesion (together with Thomas Carell). Thus, the electron acts as a catalyst for the retro-cycloaddition of thymine dimers. Giese's studies on model peptides demonstrate that long distance electron transport through peptides also occurs in a hopping reaction with the aromatic side chains of amino acids as stepping stones. 7) Photocleavable Linkers: Experiments with bioorganic radicals led to the conclusion that radicals can trigger ionic reactions. The mechanism was elucidated by kinetic experiments, spectroscopic measurements (CIDNP), product analysis, and quantum chemical calculations (together with Hendrik Zipse). An application of these mechanistic studies led to new photocleavable linkers for the combinatorial chemistry on solid support. Using photocleavable protecting groups with different absorption maxima chromatic orthogonality was developed and applied to peptide synthesis (together with Christian Bochet). For the first time also primary and secondary amines could be released by photochemical C,N-bond cleavage. A novel method for the detection of single nucleotide polymorphisms (SNPs) of genes, which takes advantage of a photocleavable nucleotide, is Giese's latest development in this area. Through this body of work, Prof. Giese has been one of the most influential scientists in the field of radical chemistry. He has been a driving force for the further development of the area for decades. Bernd, we wish you a happy birthday and thank all scientists and friends who contributed to this special issue.