F. Matthias Bickelhaupt

F. Matthias Bickelhaupt
Vrije Universiteit Amsterdam | VU · Department of Chemistry and Pharmaceutical Sciences

Prof. Dr.

About

574
Publications
75,156
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29,066
Citations
Citations since 2016
222 Research Items
14879 Citations
201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500
Introduction
Matthias Bickelhaupt currently works at the Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam. Matthias does research in Theoretical Chemistry and Catalysis. One of their current projects is 'Understanding Reactivity of Various Cycloaddition Reactions.'
Additional affiliations
January 2013 - October 2013
Warsaw University of Technology
Position
  • Professor
December 2012 - present
Radboud University
Position
  • Extraordinary Professor
January 2006 - December 2011
Universitat de Girona

Publications

Publications (574)
Article
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The iron‐catalyzed oxidative addition of C(spn)–X bonds (n = 1–3 and X = H, CH3, Cl) in archetypal model substrates H3C–CH2–X, H2C=CH–X and HC≡C–X to Fe(CO)4 was investigated using relativistic density functional theory at ZORA‐OPBE/TZ2P. The C(spn)–X bonds become substantially stronger going from C(sp3)–X to C(sp2)–X to C(sp)–X, whereas the oxidat...
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We have quantum chemically studied the base‐catalyzed Diels‐Alder (DA) reaction between 3hydroxy‐2‐pyrone and N‐methylmaleimide using dispersion‐corrected density functional theory. The uncatalyzed reaction is slow and is preceded by the extrusion of CO2 via a retro‐DA reaction. Base catalysis, e.g., by triethylamine, lowers the reaction barrier up...
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The traditional and widespread rationale behind the stability trend of alkyl-substituted carbocations is incomplete.
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The traditional and widespread rationale behind the stability trend of alkyl-substituted carbocations is incomplete. Through state-of-the-art quantum chemical analyses, we quantitatively established a generally overlooked driving force behind the stability...
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The C–H bond of the methylidyne radical, CH•, is abnormally long and weak, even longer and weaker than that of methane, CH4. This is remarkable given the fact that the C–H bond has been shown to contract as the number of substituents around the pertinent carbon atom decreases (e.g., from ethane to ethene to ethyne) because of the accompanying reduc...
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Simple mathematical models can serve to reveal the essence of experimental phenomena and scientific concepts. The particle in a box (PIB), for example, is widely used in undergraduate programs to teach the quantum mechanical principles behind the UV-vis spectra of conjugated polyenes and polyynes. In this work, the particle on a ring (POR) and the...
Article
The gauche conformer in 1-X,2-Y-disubstituted ethanes, that is, the staggered orientation in which X and Y are in closer contact, is only favored for relatively small substituents that do not give rise to large X···Y steric repulsion. For more diffuse substituents, weakly attractive orbital interactions between antiperiplanar bonds (i.e., hyperconj...
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Hierarchical, convergent ab initio benchmark computations were performed followed by a systematic analysis of DFT performance for five pericyclic reactions comprising Diels-Alder, 1,3-dipolar cycloaddition, electrocyclic rearrangement, sigmatropic rearrangement, and double group transfer prototypes. Focal point analyses (FPA) extrapolating to the a...
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We have quantum chemically investigated how methyl substituents affect the stability of alkyl radicals Me m H 3‐m C • and the corresponding Me m H 3‐m C–X bonds (X = H, CH 3 , OH; m = 0 ‐ 3) using density functional theory at M06‐2X/TZ2P. The state‐of‐the‐art in physical organic chemistry is that alkyl radicals are stabilized upon an increase in th...
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We have quantum chemically investigated how methyl substituents affect the stability of alkyl radicals Me m H 3‐m C • and the corresponding Me m H 3‐m C–X bonds (X = H, CH 3 , OH; m = 0 ‐ 3) using density functional theory at M06‐2X/TZ2P. The state‐of‐the‐art in physical organic chemistry is that alkyl radicals are stabilized upon an increase in th...
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We have quantum chemically explored the competition between the SN2 and SN2' pathways for X− + H2C=CHCH2Y (X, Y = F, Cl, Br, I) using a combined relativistic density functional theory and coupled-cluster theory approach. Bimolecular nucleophilic substitution reactions at allylic systems, i.e., Cy=Cb–Ca–Y, bearing a leaving-group at the a-position,...
Article
Imidazole-based compounds are widely found in natural products, synthetic molecules, and biomolecules. Noncovalent interactions between the imidazole ring and other functional groups play an important role in determining the function of diverse molecules. However, there is a limited understanding of the underlying noncovalent interactions between i...
Article
We discuss fundamental aspects of the EDA-NOCV method and we address some critical comments that have recently been made. The EDA-NOCV method unlike most other methods focuses on the process of the bond formation between the interacting species and not only on the analysis of the finally formed bond. This is demonstrated using LiF as example, which...
Cover Page
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Invited for the cover of this issue are Pascal Vermeeren, Trevor A. Hamlin, and F. Matthias Bickelhaupt of the TheoCheM group at the Vrije Universiteit Amsterdam. The cover art depicts how ionizing the dienophile lowers the Diels–Alder reaction barrier between 1,3‐butadiene and acrylaldehyde by reducing the destabilizing steric Pauli repulsion and...
Cover Page
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Ionization of the dienophile is an effective method to enhance the Diels–Alder reaction between buta‐1,3‐diene and acrylaldehyde. The origin of this ionization catalysis is both a reduction in steric Pauli repulsion and simultaneous enhancement of the orbital interactions between the reactants. Our work demonstrates the similarities and differences...
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We have quantum chemically studied the palladium‐mediated activation of C(spn)–X bonds (n = 1–3; X = F, Cl, Br, I) in the archetypal model substrates H3C–CH2–X, H2C=CH–X, and HC≡C–X by a model bare palladium catalyst, using relativistic density functional theory at ZORA‐BLYP/TZ2P. The bond activation reaction barrier decreases, for all sp‐hybridize...
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The C–X bond activation (X = H, C) of a series of substituted C(n°)–H and C(n°)–C(m°) bonds with C(n°) and C(m°) = H3C– (methyl, 0°), CH3H2C– (primary, 1°), (CH3)2HC– (secondary, 2°), (CH3)3C– (tertiary, 3°) by palladium were investigated using relativistic dispersion‐corrected density functional theory at ZORA‐BLYP‐D3(BJ)/TZ2P. We pinpoint the eff...
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We have studied the catalytic effect of ionization on the Diels‐Alder reaction between 1,3‐butadiene and acrylaldehyde using relativistic density functional theory (DFT). Removal of an electron from the dienophile, acrylaldehyde, significantly accelerates the Diels‐Alder reaction and shifts the reaction mechanism from concerted asynchronous for the...
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Nε-Methylation of lysine residues in histones plays an essential role in the regulation of eukaryotic transcription. The ‘highest’ methylation mark, Nε-trimethyllysine, is specifically recognised by Nε-trimethyllysine binding ‘reader’ domains, and undergoes demethylation, as catalysed by 2-oxoglutarate dependent JmjC oxygenases. We report studies o...
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It has been experimentally observed that water–ice-embedded polycyclic aromatic hydrocarbons (PAHs) form radical cations when exposed to vacuum UV irradiation, whereas ammonia-embedded PAHs lead to the formation of radical anions. In this study, we explain this phenomenon by investigating the fundamental electronic differences between water and amm...
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Invited for this month's cover are the groups of Célia Fonseca Guerra at the Vrije Universiteit Amsterdam and Leiden University, Giampaolo Barone from the Università degli Studi di Palermo, and F. Matthias Bickelhaupt at Vrije Universiteit Amsterdam and Radboud University Nijmegen. The cover picture shows the four primary interaction components (hy...
Cover Page
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The front cover provided by the TheoCheM group from Vrije Universiteit Amsterdam shows the four primary interaction components (hydrogen bonding, cross-terms, base stacking, and solvation) that determine the stability of B-DNA duplexes. Quantum chemical analyses identify an interplay between the stabilizing hydrogen bonds between nucleotides that d...
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We have quantum chemically studied the iron‐mediated C–X bond activation (X = H, Cl, CH3) by d8‐FeL4 complexes using relativistic density functional theory at ZORA‐OPBE/TZ2P. We find that by either modulating the electronic effects of a generic iron‐catalyst by a set of ligands, that is, CO, BF, PH3, BN(CH3)2, or by manipulating structural effects...
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We have quantum chemically analyzed the influence of nucleotide composition and sequence (that is, order) on the stability of double-stranded B-DNA triplets in aqueous solution. To this end, we have investigated the structure and bonding of all 32 possible DNA duplexes with Watson–Crick base pairing, using dispersion-corrected DFT at the BLYP-D3(BJ...
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Boronic acids are Lewis acids that exist in equilibrium with boronate forms in aqueous solution. Here we experimentally and computationally investigated the Lewis acidity of 2,6-diarylphenylboronic acids, specially designed phenylboronic acids that possess two flanking aromatic rings with tunable aromatic character. Hammett analysis of 2,6diarylphe...
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We have studied the palladium-mediated activation of C(spn)–X bonds (n = 1–3 and X = H, CH3, Cl) in archetypal model substrates H3C–CH2–X, H2C=CH–X and HC≡C–X by catalysts PdLn with Ln = no ligand, Cl–, and (PH3)2, using relativistic density functional theory at ZORA-BLYP/TZ2P. The oxidative addition barrier decreases along this series, even though...
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We have quantum chemically investigated how solvation influences the competition between the SN2 and E2 pathways of the model F– + C2H5Cl reaction. The system is solvated in a stepwise manner by going from the gas phase, then via microsolvation of one to three explicit solvent molecules, then last to bulk solvation using relativistic density functi...
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Atom size, not electronegativity difference, determines C−X bond strength, which weakens from X=F to I. In their Communication (DOI: 10.1002/chem.202103544), M. Bickelhaupt et al. reveal that, as the atom size increases, it is the increase in steric Pauli repulsion that weakens the C−X bond, and not the weakening of the orbital interaction (which,...
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We have quantum chemically analyzed element-element bonds of archetypal HnX-YHn molecules (X, Y = C, N, O, F, Si, P, S, Cl, Br, I), using density functional theory. One purpose is to obtain a set of consistent homolytic bond dissociation energies (BDE) for establishing accurate trends across the periodic table. The main objective is to elucidate th...
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The concept of dipolar repulsion has been widely used to explain several phenomena in organic chemistry, including the conformational preferences of carbonyl compounds. This model, in which atoms and bonds are viewed as point charges and dipole moment vectors, respectively, is however oversimplified. To provide a causal model rooted in quantitative...
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The catalytic effect of various Lewis acids (LAs) on the ene reaction between propene (ene) and but‐3‐en‐2‐one (enophile) was studied quantum chemically using density functional theory and with coupled‐cluster theory. The studied LAs efficiently accelerate the ene reaction by lowering the reaction barrier up to 12 kcal mol–1 compared to the uncatal...
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Asynchronicity in Diels-Alder reactions plays a crucial role in determining the height of the reaction barrier. Currently, the origin of asynchronicity is ascribed to the stronger orbital interaction between the diene and the terminal carbon of an asymmetric dienophile, which shortens the corresponding newly formed C–C bond and hence induces asynch...
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The reactivity of phenothiazine ( PS ), phenoselenazine ( PSE ), and phenotellurazine ( PTE ) with different reactive oxygen species (ROS) has been studied using density functional theory (DFT) in combination with the QM‐ORSA (Quantum Mechanics‐based Test for Overall Free Radical Scavenging Activity) protocol for an accurate kinetic rate calculatio...
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Brønsted acid‐catalyzed inverse‐electron demand (IED) aza‐Diels‐Alder reactions between 2‐aza‐dienes and ethylene were studied using quantum chemical calculations. The computed activation energy systematically decreases as the basic sites of the diene progressively become protonated. Our activation strain and Kohn‐Sham molecular orbital analyses tr...
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The α-effect is a “reactivity booster” that affords the less basic peroxide (HOO⁻) the edge over hydroxide (HO⁻) in the Grand Prix of SN2 Reactivity! In their Research Article (DOI: 10.1002/anie.202106053), Trevor A. Hamlin et al. equip researchers with two criteria that α-nucleophiles need to fulfill to exhibit an α-effect: (i) a small HOMO lobe o...
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Der α‐Effekt ist ein „Reaktivitäts‐Booster“, der dem weniger basischen Peroxid (HOO−) den Vorteil gegenüber Hydroxid (HO−) im Grand Prix der SN2‐Reaktivität verschafft! In ihrem Forschungsartikel (DOI: 10.1002/ange.202106053) stellen Trevor A. Hamlin et al. zwei Kriterien auf, die α‐Nucleophile erfüllen müssen, um einen α‐Effekt zu zeigen: (i) ein...
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We have analyzed the structure and stability of archetypal pnictogen-bonded model complexes D3PnA- (Pn = N, P, As, Sb; D, A = F, Cl, Br) using state-of-the-art relativistic density functional calculations at the ZORA-M06/QZ4P level. We have accomplished two tasks: (i) to compute accurate trends in pnictogen-bond strength based on a set of consisten...
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Chemical reactions are ubiquitous in the universe, they are at the core of life, and they are essential for industrial processes. The drive for a deep understanding into how something occurs, in this case, the mechanism of a chemical reaction and the factors controlling its reactivity, is intrinsically valuable and an innate quality of humans. The...
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The α‐effect is a term used to explain the dramatically enhanced reactivity of α‐nucleophiles (R–Y–X:– ) compared to their parent normal nucleophile (R–X:– ) by deviating from the classical Brønsted‐type reactivity–basicity relationship. The exact origin of this effect is, however, still heavily under debate. In this work, we have quantum chemicall...
Article
Full-text available
The α‐effect is a term used to explain the dramatically enhanced reactivity of α‐nucleophiles (R–Y–X:– ) compared to their parent normal nucleophile (R–X:– ) by deviating from the classical Brønsted‐type reactivity–basicity relationship. The exact origin of this effect is, however, still heavily under debate. In this work, we have quantum chemicall...
Article
The cover image is based on the Full Paper Chalcogen bonds: Hierarchical ab initio benchmark and density functional theory performance study by Lucas de Azevedo Santos et al., https://doi.org/10.1002/jcc.26489.
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Invited for this month's cover are the groups of Prof. Dr. Teodorico C. Ramalho (Federal University of Lavras and University Hradec Kralove) and Prof. Dr. F. Matthias Bickelhaupt (Vrije Universiteit Amsterdam and Radboud University). The cover picture shows the key message of their work, that is, the covalency of the chalcogen bonds, in an elegantl...
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The Front Cover shows the key message of our work, that is, the covalency of the chalcogen bonds, in an elegantly simple and attractive manner. To that end, the chalcogen bonds are represented by schematic 3D structures of the bond donor D2Ch and the bond acceptor A–, and their attractive interaction in green. Then, a colorful molecular orbital (MO...
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ConspectusOrganic chemistry has undoubtedly had a profound impact on humanity. Day in and day out, we find ourselves constantly surrounded by organic compounds. Pharmaceuticals, plastics, fuels, cosmetics, detergents, and agrochemicals, to name a few, are all synthesized by organic reactions. Very often, these reactions require a catalyst in order...
Cover Page
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In s–p hybridization, the contraction of C−H and C−C bonds as the carbon atom involved varies from sp3 to sp2 to sp is a fundamental and ubiquitous phenomenon in chemistry. Using state‐of‐the‐art quantum chemical computations, this work uncovers that these bonds do not contract due to the increasing percentage of s‐character of the hybrid orbital a...
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We have quantum chemically studied the catalytic effect of various weakly interacting Lewis acids (LAs) across the periodic table, based on hydrogen (Group 1), pnictogen (Group 15), chalcogen (Group 16), and halogen (Group 17) bonds, on the Diels‐Alder cycloaddition reaction between 1,3‐butadiene and methyl acrylate using relativistic density funct...
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We have studied the activation of dihydrogen by metallylenes using relativistic density functional theory (DFT). Our detailed activation strain and Kohn–Sham molecular orbital analyses have quantified the physical factors behind the decreased reactivity of the metallylene on going down Group 14, from carbenes to stannylenes. Along this series, the...
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We have quantum chemically analyzed the structure and stability of archetypal chalcogen-bonded model complexes D2 Ch⋅⋅⋅A- (Ch = O, S, Se, Te; D, A = F, Cl, Br) using relativistic density functional theory at ZORA-M06/QZ4P. Our purpose is twofold: (i) to compute accurate trends in chalcogen-bond strength based on a set of consistent data; and (ii) t...
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We have quantum chemically investigated the rotational isomerism of 1,2‐dihaloethanes XCH 2 CH 2 X (X = F, Cl, Br, I) at ZORA‐BP86‐D3(BJ)/QZ4P. Our Kohn‐Sham molecular orbital (KS‐MO) analyses reveal that hyperconjugative orbital interactions favor the gauche conformation in all cases (X = F ‐ I), not only for X = F as in the current model of this...
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We have performed a hierarchical ab initio benchmark and DFT performance study of D2 Ch•••A- chalcogen bonds (Ch = S, Se; D, A = F, Cl). The ab initio benchmark study is based on a series of ZORA-relativistic quantum chemical methods [HF, MP2, CCSD, CCSD(T)], and all-electron relativistically contracted variants of Karlsruhe basis sets (ZORA-def2-S...