Henk Buck (7 February 1930 – 27 November 2023) was a Dutch organic chemist. He was born in Dordrecht on 7 February 1930. Buck studied at the University of Leiden where he received his PhD in 1959. He got a lectorship at the university in Theoretical Organic Chemistry in 1964. For his research he received the Golden Medal of the Royal Netherlands Chemical Society in 1967. In 1970 he was appointed professor of Physical Organic Chemistry and Organic Chemistry at the University of Technology in Eindhoven. Because there was no chair for Theoretical Chemistry and Biochemistry he gave lectures in organic chemistry, physical organic chemistry, theoretical organic chemistry, biochemistry and biotechnology. From 1988 to 1991 he was Dean of the Chemical Faculty. For his scientific contributions he became a member of the Royal Netherlands Academy of Arts and Sciences in 1979. During his scientific career he published more than 300 scientific papers spread over a large area of the chemical field. Under his supervision 43 chemical engineers obtained their PhD. The end of his career came prematurely because of a publication in Science in 1990 regarding a possible cure for cancer that had to be retracted because of flawed research.
Research His research in Leiden and later in Eindhoven was focused on organic chemistry as the homogeneous catalysis of the oxidation of hydrocarbons with stable carbenium ions as the pentamethylbenzyl cation Van Pelt, P. et al. (1976) "Proton acid catalyzed hydride transfer from alkanes to methylated benzyl cations. Part III: Solvated alkanes as Hydrogen-donating intermediates", Journal of the American Chemical Society,Vol. 98, pp. 5864-5870 and the chiral induction with the redox couple NADH-NAD+ in the nearly 100% stereospecific hydride transfer to ketones and imines.Vekemans, J.A.J.M. et al. (1991) "NADH model mediated reduction of C=N substrates: enantio-selective synthesis of D-and L-phenylglycinates",Thetrahedron: A symmetry, Vol.2, pp. 949–952 The latter process is controlled by the out-of-plane orientation of the carboxamide group.Donkersloot, M.C.A. et al.(1981) "The hydride-donation reaction of reduced nicotinamide adenine dinucleotide. 2.MINDO/3 and STO-3G calculations on the role of the CONH2group in enzymatic reactions", Journal of the American Chemical Society, Vol. 103, pp. 6554-6558 In the field of physical chemistry his work was directed on electron spin resonance measurements of phosphoranyl radicals with phosphorus in different geometries as the tetrahedral and the trigonal bipyramidal configuration with the unpaired electron in an equatorial or axial orientation.Aagaard, O.M. et al. (1990) "Intermolecular effects on the radiogenic formation of electron-capture phosphorus-centered Journalradicals A single-crystal ESR study of diastereoisomeric precursors", Journal of the American Chemical Society, Vol. 112, pp. 938-944 His contribution to the theoretical organic chemistry was based on Ab initio calculations of the radiationless transition of formaldehydeVan Dijk, J.M.F. et al. (1978) "Ab initio CI calculation of the radiationless transition of the 1(npi)state of formaldehyde", Journal of the Chemical Physics, Vol. 69, pp. 2462-2473 and ab initio calculations of single vibronic level fluorescence emission spectra and absolute radiative lifetimes of formaldehyde.Van Dijk, J.M.F. et al. (1978) "Ab initio CI calculation of single vibronic level fluorescence emission spectra and absolute radiative lifetimes of H2CO(1A2)", Journal of the Chemical Physics, Vol. 70, pp. 2854-2858 Further he investigated deviations of the Woodward-Hoffmann rules as the photochemical [1,3]-OH shift in 2-propen-1-ol.Dormans, G.J.M. et al. (1984) "A quantum chemical study on the mechanism of a photochemical {1,3]-OH shift in 2-propen-1-ol", Journal of the American Chemical Society, Vol. 106, pp. 1213-1216 Here the stereochemical outcome is determined by relaxation of the excited double bond. A thermal study of the cis-[1,5]-H shifts in 1,3-pentadiene showed the effect of vibrationally assisted tunneling in this geometric orientation.Dormans, G.J.M. et al. (1984) " Mechanism of the thermal [1,5]-H shift in cis 1,3-pentadiene. Kinetic isotope effect and vibrationally assisted tunneling", Journal of the American Chemical Society, Vol. 106, pp. 3253-3258
A special topic in his research was organophosphorus chemistry. An important aspect of this project was based on the possibility of phosphorus (IV) to accommodate a fifth ligand under formation of a trigonal bipyramid which shows a number of unique properties. The significance of this geometrical change has been demonstrated in the conformational transmission in DNA for the B-Z transition with alternating CpG units under selective phosphate shielding.Van Lier, J.J.C. et al. (1983) B-Z transition in methylated DNA. A quantum-chemical study", European Journal of Biochemistry, Vol. 132, pp. 55-62 This change in geometry of phosphorus was also applicable on the biochemical dynamics of cAMP.Broeders, N.L.H. et al. (1990)"A 400- and 600- MHz 1H NMR conformational study on nucleoside cyclic 3',5'PV-TBP systems. Conformational transmission induces diequatorial orientation of the 3',5'-dioxaphosphorinane ring in a nonchair conformation", Journal of the American Chemical Society, Vol. 106, pp. 7475-7482 Because of the importance of shielding, the OCH3 group was introduced as substitute for O− in the study of intermediates for conformational transmission. This also resulted in the synthesis of phosphate-methylated DNAs and RNAs. Methylphosphotriester DNAs were synthesized with 2-12 bases. Neutralization of the charge of the phosphate linkages by (specific) methylation resulted in methylphosphotriester DNAs with very exclusive (bio)chemical properties.European Patent entitled Poly(deoxyribonucleotides), pharmaceutical compositions, use and preparation of the poly(deoxyribonucleotides) München 09-06-1993, Patent NO. 0358657 The introduction of chirality at phosphorus appeared of importance for intra- and intermolecular dynamics. These modified DNAs mimicked the behavior of natural DNA in the absence of stabilizing factors as salts, proteins, and medium factors. In fact a high site-specific hybridization affinity was obtained with complementary natural DNA. In dependence of the bases, parallel DNA could be synthesized for pyrimidine bases in which the chirality of phosphorus was decisive.Koole, L.H. et al. (1987) "A parallel right-handed duplex of the hexamer d(TPTPTPTPTPT) with phosphate triester linkages",Journal of the American Chemical Society, Vol. 109, pp. 3916-3921 Phosphate methylation also gave the possibility to synthesize a self-complementary left-handed Z-DNA mini duplex.
After a publication in Science about the inhibition of HIV-1 replication had to be retracted, because it was based on flawed research, he accepted early retirement in 1990.Buck, H.M. e.a. (1990) "Phosphate-Methylated DNA Aimed at HIV-1 RNA Loops and Integrated DNA Inhibits Viral Infectivity", Science, 13 April 1990: Vol. 248. no. 4952, pp. 208 - 212.Moody, H.M. e.a. (1990) "Inhibition of HIV-1 Infectivity by Phosphate-Methylated DNA: Retraction", Science, Vol. 250, pp. 125-126. (see The Buck-Goudsmit controversy)
At home without any academic support he wrote several articles based on quantum chemical calculations focused on the dynamics of organic reactions, electron spin resonance of organophosphorus radicals and the hybridization affinity of methylphosphotriester DNA and RNA. The latter subject is published as review articles in Nucleosides, Nucleotides & Nucleic Acids. In these reviews he gives also a description and explanation of the chemical and corresponding biochemical results of the methylphosphotriester DNA, RNA and related systems. This contribution that is mainly based on the work at Eindhoven also consists of new insights in solid-phase synthesis, B-Z transition, and methyl transfer reactions connected with replicational and transcriptional silencing. Special attention is given to the effect of phosphate shielding on duplex stability. Models based on molecular mechanics calculations and recent density functional ab initio calculations support the impact of phosphate shielding at the various levels of stability of the DNA duplex.
The Buck-Goudsmit controversy In the mid-80s Henk Buck focused his research on the use of antisense DNA as an inhibitor of virus replication. Paul C. Zamecnik is generally regarded as the founder of this technique,Zamecnik P.C. e.a. (1978) "Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide." Proceedings of the National Academy of Sciences of the United States of America January;75(1)pp. 280-4 but already in 1971 Paul S. Miller created short phosphate methylated DNA-fragments, and considered the possibility of using this as a means of influencing DNA-replication.Miller P.S. e.a (1971) "Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates." Journal of the American Chemical Society. Vol 93, pp. 6657-65 Buck's research group focused on the use of this phosphate methylated DNA, in particular because of its neutral electrical properties. In several publications the selectivity and duplex forming were reported.
The strong growth of HIV-infections in those days, commercial interests and patent rights led to the decision to cooperate with the virologist Jaap Goudsmit of the Academic Medical Center of Amsterdam University. Jaap Goudsmit required longer DNA-strands, though, than the ones Buck was testing so far, so a new synthesis route was developed. Jaap Goudsmit tested the new strands on samples of HIV and reported the inhibition of the virus replication.
The results were published in Science on April 13, 1990.
On the eve of the publication, the University of Eindhoven made the news public. It resulted in excited media attention in the Netherlands, and under the pressure Buck publicly stated that he assumed that AIDS would be of the past in a couple of years, although it was agreed not to make such claims. Afterwards he explained, he deliberately had said this to raise more funds for his research, although much later he defended himself by saying that he was provoked by the reporter.