François Diederich’s legacy

For over four decades, François Diederich was an inspiration in organic, biological, and materials chemistry. His work influenced generations of chemists, his visions changed many aspects modern With passing 2020, we have lost a mentor, friend, wonderful human being. He will be missed by colleagues, students, friends, family. In the past has profoundly contributed to different fields ranging from chemical biology molecular recognition advanced based on carbon-rich acetylenic architectures fullerenes.These findings made major contribution enhancing rational lead development optimization pharmaceutical crop-protection industries.With challenge, however, comes creative solutions, John Anthony (PhD 1994), now professor at University Kentucky, tells story how he others would capitalize François’s love peanuts leaving bowl them laboratory so that they could talk with him when came “nibble” them. born July 9, 1952, Ettelbrück, small city just north Luxembourg City Grand-Duchy Luxembourg. attended high school Lycée Classique Diekirch, attributed fascination chemistry teacher, Mr. Jean Mootz, whose courses “… were spiced spectacular experiments; furthermore, it possible free afternoons pursue little projects well-equipped laboratories school.”1ProfileFrançois Diederich: applied biosciences, ETH Zürich, Switzerland.Org. Biomol. Chem. 2003; 1: xii-xiiihttps://doi.org/10.1039/B300290JCrossref Google Scholar After school, moved Heidelberg, Germany, where received diploma 1977. then began studies developed carbon compounds during doctoral dissertation, completed first synthesis kekulene2Diederich F. Staab H.A. Benzenoid versus annulenoid aromaticity: properties Kekulene.Angew. Int. Ed. 1978; 17: 372-374Crossref Scopus (132) while working Prof. Heinz Staab. From 1979 1981, got taste life United States as post-doctoral researcher lab Orville Chapman California, Los Angeles (UCLA). At time, toward total C60, which fostered Diederich’s interests design polymeric allotropes. These topics became consistent research theme throughout career some most recognized discoveries contributions. time UCLA also cultured another passion, host-guest supramolecular chemistry, through interactions Donald Cram, who often spoke about great respect admiration. returned Germany 1981 for habilitation Max Planck Institute Medical Research (Heidelberg), this feature prominently research, addition molecules. Upon completion (1985), back become organic remained next 7 years. 1992, left accept position ETH-Zurich retired teaching duties 2017 but research-active until died September 23, after battle cancer. Throughout career, assumed significant leadership role within community, both locally internationally. chair Department Chemistry Applied Biosciences (2002–2004), served twice vice (2001–2002 2004–2005). Among dozens other “service” positions, New Swiss Chemical Society (1994–2001), member German (GDCh) Board Directors (2008–2015), president GDCh (2011–2012); March 2019, awarded its highest honor: honorary membership. editorial board Angewandte Chemie (1995–2013) subsequently journal’s international advisory board. Finally, mention fierce supporter International Symposium Novel Aromatics (ISNA) conference series; sent coworkers attend, well organized ISNA-13 Within field conjugated molecules physical ISNA remains anticipated each year occurs, large part because enthusiasm support. honored course very impressive list awards. National Academy Sciences, American Arts Spanish Royal Sciences foreign associate US Sciences. number prestigious awards, including Breslow Award Biomimetic Cope August-Wilhelm-von-Hofmann Adolf-von-Baeyer-Denkmünzen Awards GDCh. Israel Society, 2005 Order Merit Grand Duchy fullerenes. Work all these areas always highly driven characterized blend synthetic physical-organic methodology. had impact contemporary understanding weak intermolecular biological complexation.3Meyer E.A. Castellano R.K. Interactions aromatic rings recognition.Angew. 42: 1210-1250Crossref PubMed (3066) one scientists investigate complexation neutral water, performed quantitative series elegantly designed, potent cyclophane receptors.4Diederich Complexation hosts.Angew. 1988; 27: 362-386Crossref (455) comprehensive investigations apolar solutes (aromatic alicyclic substrates steroids) cyclophanes solvents covering entire polarity range water benzene, showed biotic abiotic is not special rather predictable means linear free-energy relationships empirical solvent parameters. thermodynamic led profound extension hydrophobically association processes. demonstrated tight strongly enthalpy, gain cohesive energy dispersive are driving forces.5Smithrud D.B. Enthalpically cyclophane-arene inclusion complexation: solvent-dependent calorimetric studies.J. Am. Soc. 1991; 113: 5420-5426Crossref (216) Since seminal, cited work, enthalpy-driven (the “non-classical hydrophobic effect”) been numerous force mid-1990s on, unique, multi-dimensional approach recognition. combined extensive experimental database mining discover quantify individual bonding interactions. Being successfully apply structure-based de novo approaches,6Obst U. Gramlich V. Weber L. Banner D.W. Design novel, nonpeptidic thrombin inhibitors structure thrombin–inhibitor complex.Angew. 1995; 34: 1739-1742Crossref (56) non-peptidic small-molecule enzyme admirable intuition. recognize peptidic H–Cα–C=O fragments provide pronounced fluorophilic environment.7Fischer F.R. Schweizer W.B. Molecular torsion balances: evidence favorable orthogonal dipolar between fluorine amide groups.Angew. 2007; 46: 8270-8273Crossref (92) Scholar,8Paulini R. Müller K. Orthogonal multipolar structural biology.Angew. 2005; 44: 1788-1805Crossref (409) A scan serine protease revealed attractive nature C–F···C=O interactions, later quantified model system torsional balance.7Fischer short distances, bond dipoles prefer array particular, C=O···C=O (quantified balance system) make important contributions protein structures protein-ligand complexation.8Paulini Scholar,9Fischer Wood P.A. Allen F.H. carbonyl groups.Proc. Natl. Acad. Sci. USA. 2008; 105: 17290-17294Crossref (98) context, collaboration Klaus (Roche), defined those environments enable organofluorine energetically unfavorable.10Müller Faeh C. Fluorine pharmaceuticals: looking beyond intuition.Science. 317: 1881-1886Crossref (4481) hottest addressing question much enthalpy can gained displacement crystallographically localized upon ligand binding. example, ligand-important additional parts ΔG up 2 kcal/mol, whereas another, found conserved cluster solvating two Asp side chains best replaced balance.11Ellermann M. Jakob-Roetne Lerner Borroni E. Schlatter D. Roth Ehler A. Rudolph M.G. active site catechol-o-methyltransferase: replacement molecule imported bisubstrate inhibitor.Angew. 2009; 48: 9092-9096Crossref (32) industries. As already mentioned, heart since textbook “kekulene” dissertation Heidelberg. rapidly leading scientist acetylene-based functional scaffolds push-pull chromophores optoelectronic applications. broad area molecular-shape creativity successful implementation function design. unique construction kit scaffolding, consisting tetraethynylethenes, 1,2-diethynylethenes, 1,3-diethynylallenes, 1,4-di- tetraethynylbutatrienes, triethynylmethanes, 1,1,2,2-tetraethynylethanes.12Nielsen M.B. Conjugated oligoenynes diethynylethene unit.Chem. Rev. 1837-1867Crossref (228) multitude fascinating constructed outstanding synthesis.12Nielsen Another typical example elegant routes cyclocarbons—all-acetylenic all-carbon rings, such cyclo-Cn (n = 18, 24, or 30), π-systems—as demonstration their coalescence ion-molecule gas-phase reactions under formation fullerenes, organic-synthetic spheres.13Diederich Rubin Y. Knobler C.B. Whetten R.L. Schriver K.E. Houk K.N. Li All-carbon molecules: generation cyclo[18]carbon stable precursor.Science. 1989; 245: 1088-1090Crossref (94) This program greatly expanded fundamental technological perspectives stimulated worldwide. true breakthrough accomplished new “click”-type reaction preparation non-planar charge-transfer chromophores. Donor-substituted electron-rich alkynes undergo quantitative, fully atom-economic transformation via formal [2 + 2]cycloaddition, followed retro-electrocyclization, gives donor-substituted 1,1,4,4-tetracyanobuta-1,3-dienes (TCBD) featuring efficient intramolecular third-order nonlinear optical properties.14Kato S. Non-planar chromophores.Chem. Commun. 2010; 1994-2006Crossref (218) Some TCBDs form high-quality films beam epitaxy use telecommunication devices. 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) adds alkynes, novel used preparing class super-acceptors intra- charge transfer ease.14Kato transformations taken groups materials. molecules, pioneer fullerene chemistry—he discovered higher fullerenes.15Diederich Ettl Beck Alvarez Anz Sensharma Wudl Khemani K.C. Koch The fullerenes: isolation characterization C76, C84, C90, C94, C70O, oxide D5h-C70.Science. 252: 548-551Crossref (632) Today, fullerenes considerable interest view superior electron-accepting capacity endohedral metal-ion complexes. invented regio- stereoselective, tether- template-controlled multifunctionalized today methods choice worldwide stereoselective C60 multiple adducts.16Diederich Kessinger Templated regioselective chemistry.Acc. Res. 1999; 32: 537-545Crossref (267) inherently chiral (C76-D2) enantioselective derivatives, inventions chirality Diederich. thus created completely chapter stereochemistry.17Thilgen Structural chemistry--a journey chirality.Chem. 2006; 106: 5049-5135Crossref (427) extraordinary potential chemistry.18Diederich Gomez-Lopez Supramolecular chemistry.Chem. 28: 263-277Crossref (723) others, examples systems group include fullerene-containing rotaxanes catenanes, fullerene-crown ether conjugates act electrochemical sensors alkali metal cations, photoactive fullerene-diporphyrin-sheet dyads. resulted several long-standing collaborations friendships, Maurice Gross Jean-Paul Gisselbrecht (University Strasbourg), Luis Echegoyen Texas El Paso), others. Overall, various logically interconnected, exemplified multidimensional crossed interdisciplinary boundaries interfaces science maintaining exceptional strength targeted synthesis, studies, chemical-structure-based leaves behind only legacy substantial mentorship. researchers worked François, authors relay exceptionally rewarding, especially given breadth presented, discussed, debated weekly meetings, example. On hand, busy, times challenging find meet him. impeccable standards learning live intimidating. Little did know, valuable attributes take away our François—the ability critically assess results, determine importance, ultimately produce error-free section (as us quickly learned, uncanny immediately singular mistake page data). During 125 PhD students 100 researchers, whom gone influential careers industry academia. Amazingly, more than quarter established own independent Science vision general particular group. passing, close family.Left right: Yves Rubin, Sophie (Wilkinson) Rovner, summer 1985. Photo courtesy Rubin.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Typical together calculated complexes formed p-dimethoxybenzene (top) pyrene (bottom).View (PPT)François friends ISNA-15 Taipei 2013. Left Diederich, Nazario Martin, Jean-Luc Brédas, Müllen, Eichii Nakamura. Jyun-Hwei Hwang.View (PPT)(A) Typical (B) enantiomers C76-D2. (C) catenane prepared Stoddart.View (PPT)Friends, family, colleagues retirement symposium Zurich June 2019. Rolf Häfliger.View 2009. Jens Hornung Manuel Ellermann.View (PPT) We thank Carlo Tilgen, Ken-Tsung Wong, Larry Scott help tracking down pictures photographers article.