@article{WeiserCuiDewhurstetal.2023,
  author    = {Weiser, Jonas and Cui, Jingjing and Dewhurst, Rian D. and Braunschweig, Holger and Engels, Bernd and Fantuzzi, Felipe},
  title     = {Structure and bonding of proximity-enforced main-group dimers stabilized by a rigid naphthyridine diimine ligand},
  series = {Journal of Computational Chemistry},
  volume    = {44},
  journal   = {Journal of Computational Chemistry},
  number    = {3},
  doi       = {10.1002/jcc.26994},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312586},
  pages     = {456 -- 467},
  year      = {2023},
  abstract  = {The development of ligands capable of effectively stabilizing highly reactive main-group species has led to the experimental realization of a variety of systems with fascinating properties. In this work, we computationally investigate the electronic, structural, energetic, and bonding features of proximity-enforced group 13-15 homodimers stabilized by a rigid expanded pincer ligand based on the 1,8-naphthyridine (napy) core. We show that the redox-active naphthyridine diimine (NDI) ligand enables a wide variety of structural motifs and element-element interaction modes, the latter ranging from isolated, element-centered lone pairs (e.g., E = Si, Ge) to cases where through-space π bonds (E = Pb), element-element multiple bonds (E = P, As) and biradical ground states (E = N) are observed. Our results hint at the feasibility of NDI-E2 species as viable synthetic targets, highlighting the versatility and potential applications of napy-based ligands in main-group chemistry.},
  language  = {en}
}
@article{SchmidtFantuzziKlopfetal.2021,
  author    = {Schmidt, Paul and Fantuzzi, Felipe and Klopf, Jonas and Schr{\"o}der, Niklas B. and Dewhurst, Rian D. and Braunschweig, Holger and Engel, Volker and Engels, Bernd},
  title     = {Twisting versus delocalization in CAAC- and NHC-stabilized boron-based biradicals: the roles of sterics and electronics},
  series = {Chemistry - A European Journal},
  volume    = {27},
  journal   = {Chemistry - A European Journal},
  number    = {16},
  doi       = {10.1002/chem.202004619},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256636},
  pages     = {5160-5170},
  year      = {2021},
  abstract  = {Twisted boron-based biradicals featuring unsaturated C\(_2\)R\(_2\) (R=Et, Me) bridges and stabilization by cyclic (alkyl)(amino)carbenes (CAACs) were recently prepared. These species show remarkable geometrical and electronic differences with respect to their unbridged counterparts. Herein, a thorough computational investigation on the origin of their distinct electrostructural properties is performed. It is shown that steric effects are mostly responsible for the preference for twisted over planar structures. The ground-state multiplicity of the twisted structure is modulated by the σ framework of the bridge, and different R groups lead to distinct multiplicities. In line with the experimental data, a planar structure driven by delocalization effects is observed as global minimum for R=H. The synthetic elusiveness of C\(_2\)R\(_2\)-bridged systems featuring N-heterocyclic carbenes (NHCs) was also investigated. These results could contribute to the engineering of novel main group biradicals.},
  language  = {en}
}
@article{SaalfrankFantuzziKupferetal.2020,
  author    = {Saalfrank, Christian and Fantuzzi, Felipe and Kupfer, Thomas and Ritschel, Benedikt and Hammond, Kai and Krummenacher, Ivo and Bertermann, R{\"u}diger and Wirthensohn, Raphael and Finze, Maik and Schmid, Paul and Engel, Volker and Engels, Bernd and Braunschweig, Holger},
  title     = {cAAC-Stabilized 9,10-diboraanthracenes—Acenes with Open-Shell Singlet Biradical Ground States},
  series = {Angewandte Chemie International Edition},
  volume    = {59},
  journal   = {Angewandte Chemie International Edition},
  number    = {43},
  doi       = {10.1002/anie.202008206},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217795},
  pages     = {19338 -- 19343},
  year      = {2020},
  abstract  = {Narrow HOMO-LUMO gaps and high charge-carrier mobilities make larger acenes potentially high-efficient materials for organic electronic applications. The performance of such molecules was shown to significantly increase with increasing number of fused benzene rings. Bulk quantities, however, can only be obtained reliably for acenes up to heptacene. Theoretically, (oligo)acenes and (poly)acenes are predicted to have open-shell singlet biradical and polyradical ground states, respectively, for which experimental evidence is still scarce. We have now been able to dramatically lower the HOMO-LUMO gap of acenes without the necessity of unfavorable elongation of their conjugated π system, by incorporating two boron atoms into the anthracene skeleton. Stabilizing the boron centers with cyclic (alkyl)(amino)carbenes gives neutral 9,10-diboraanthracenes, which are shown to feature disjointed, open-shell singlet biradical ground states.},
  language  = {en}
}
@article{RoyTroesterFantuzzietal.2021,
  author    = {Roy, Dipak Kumar and Tr{\"o}ster, Tobias and Fantuzzi, Felipe and Dewhurst, Rian D. and Lenczyk, Carsten and Radacki, Krzysztof and Pranckevicius, Conor and Engels, Bernd and Braunschweig, Holger},
  title     = {Isolation and Reactivity of an Antiaromatic s-Block Metal Compound},
  series = {Angewandte Chemie International Edition},
  volume    = {60},
  journal   = {Angewandte Chemie International Edition},
  number    = {7},
  doi       = {10.1002/anie.202014557},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224447},
  pages     = {3812 -- 3819},
  year      = {2021},
  abstract  = {The concepts of aromaticity and antiaromaticity have a long history, and countless demonstrations of these phenomena have been made with molecules based on elements from the p, d, and f blocks of the periodic table. In contrast, the limited oxidation-state flexibility of the s-block metals has long stood in the way of their participation in sophisticated π-bonding arrangements, and truly antiaromatic systems containing s-block metals are altogether absent or remain poorly defined. Using spectroscopic, structural, and computational techniques, we present herein the synthesis and authentication of a heterocyclic compound containing the alkaline earth metal beryllium that exhibits significant antiaromaticity, and detail its chemical reduction and Lewis-base-coordination chemistry.},
  language  = {en}
}
@article{RangFantuzziArrowsmithetal.2021,
  author    = {Rang, Maximilian and Fantuzzi, Felipe and Arrowsmith, Merle and Krummenacher, Ivo and Beck, Eva and Witte, Robert and Matler, Alexander and Rempel, Anna and Bischof, Tobias and Radacki, Krzysztof and Engels, Bernd and Braunschweig, Holger},
  title     = {Reduktion und Umlagerung eines Bor(I)-Carbonylkomplexes},
  series = {Angewandte Chemie},
  volume    = {133},
  journal   = {Angewandte Chemie},
  number    = {6},
  doi       = {10.1002/ange.202014167},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224409},
  pages     = {3000 -- 3005},
  year      = {2021},
  abstract  = {Bei der Einelektronenreduktion eines durch eine cyclisches (Alkyl)(amino)carben (CAAC) stabilisierten Arylborylen-Carbonylkomplexes erfolgt die Bildung eines dimeren Borylketyl-Radikalanions, bedingt durch eine intramolekulare Arylmigration zum CO Kohlenstoffatom. Computergest{\"u}tzte Analyse liefert Hinweise auf eine radikalanionische [(CAAC)B(CO)Ar]\(^{.-}\) Zwischenstufe. Weiterf{\"u}hrende Reduktion des entstandenen Komplexes liefert ein hoch nukleophiles (Boranyliden)methanolat.},
  language  = {de}
}
@article{MuellerMetaMeidneretal.2023,
  author    = {M{\"u}ller, Patrick and Meta, Mergim and Meidner, Jan Laurenz and Schwickert, Marvin and Meyr, Jessica and Schwickert, Kevin and Kersten, Christian and Zimmer, Collin and Hammerschmidt, Stefan Josef and Frey, Ariane and Lahu, Albin and de la Hoz-Rodr{\´i}guez, Sergio and Agost-Beltr{\´a}n, Laura and Rodr{\´i}guez, Santiago and Diemer, Kira and Neumann, Wilhelm and Gonz{\`a}lez, Florenci V. and Engels, Bernd and Schirmeister, Tanja},
  title     = {Investigation of the compatibility between warheads and peptidomimetic sequences of protease inhibitors — a comprehensive reactivity and selectivity study},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {8},
  issn      = {1422-0067},
  doi       = {10.3390/ijms24087226},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313596},
  year      = {2023},
  abstract  = {Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.},
  language  = {en}
}
@article{KleinJoheWagneretal.2020,
  author    = {Klein, Philipp and Johe, Patrick and Wagner, Annika and Jung, Sascha and K{\"u}hlborn, Jonas and Barthels, Fabian and Tenzer, Stefan and Distler, Ute and Waigel, Waldemar and Engels, Bernd and Hellmich, Ute A. and Opatz, Till and Schirmeister, Tanja},
  title     = {New cysteine protease inhibitors: electrophilic (het)arenes and unexpected prodrug identification for the Trypanosoma protease rhodesain},
  series = {Molecules},
  volume    = {25},
  journal   = {Molecules},
  number    = {6},
  issn      = {1420-3049},
  doi       = {10.3390/molecules25061451},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203380},
  year      = {2020},
  abstract  = {Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the S\(_N\)Ar addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases. We further elucidate an unexpected mode of action for the trypanosomal protease rhodesain using NMR spectroscopy and mass spectrometry, enzyme kinetics and various types of simulations. After hydrolysis of an ester function in the recognition sequence of a weakly active prodrug inhibitor, the liberated carboxylic acid represents a highly potent inhibitor of rhodesain (K\(_i\) = 4.0 nM). The simulations indicate that, after the cleavage of the ester, the carboxylic acid leaves the active site and re-binds to the enzyme in an orientation that allows the formation of a very stable π-complex between the catalytic dyad (Cys-25/His-162) of rhodesain and the electrophilic aromatic moiety. The reversible inhibition mode results because the S\(_N\)Ar reaction, which is found in an alkaline solvent containing a low molecular weight thiol, is hindered within the enzyme due to the presence of the positively charged imidazolium ring of His-162. Comparisons between measured and calculated NMR shifts support this interpretation},
  language  = {en}
}
@article{KleinBarthelsJoheetal.2020,
  author    = {Klein, Philipp and Barthels, Fabian and Johe, Patrick and Wagner, Annika and Tenzer, Stefan and Distler, Ute and Le, Thien Anh and Schmid, Paul and Engel, Volker and Engels, Bernd and Hellmich, Ute A. and Opatz, Till and Schirmeister, Tanja},
  title     = {Naphthoquinones as covalent reversible inhibitors of cysteine proteases — studies on inhibition mechanism and kinetics},
  series = {Molecules},
  volume    = {25},
  journal   = {Molecules},
  number    = {9},
  issn      = {1420-3049},
  doi       = {10.3390/molecules25092064},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203791},
  year      = {2020},
  abstract  = {The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the target enzyme itself yielding the free acid. Detailed kinetic and mass spectrometry studies revealed a reversible covalent binding mode. Theoretical calculations with different density functionals (DFT) as well as wavefunction-based approaches were performed to elucidate the mode of action.},
  language  = {en}
}
@article{DietschreitWagnerLeetal.2020,
  author    = {Dietschreit, Johannes C. B. and Wagner, Annika and Le, T. Anh and Klein, Philipp and Schindelin, Hermann and Opatz, Till and Engels, Bernd and Hellmich, Ute A. and Ochsenfeld, Christian},
  title     = {Predicting \(^{19}\)F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase-Inhibitor Complex},
  series = {Angewandte Chemie International Edition},
  volume    = {59},
  journal   = {Angewandte Chemie International Edition},
  number    = {31},
  doi       = {10.1002/anie.202000539},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214879},
  pages     = {12669 -- 12673},
  year      = {2020},
  abstract  = {The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor-protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable \(^{19}\)F chemical-shift predictions to deduce ligand-binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the \(^{19}\)F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein-inhibitor conformations as well as monomeric and dimeric inhibitor-protein complexes, thus rendering it the largest computational study on chemical shifts of \(^{19}\)F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area.},
  language  = {en}
}
@article{BruneckerMuessigArrowsmithetal.2020,
  author    = {Brunecker, Carina and M{\"u}ssig, Jonas H. and Arrowsmith, Merle and Fantuzzi, Felipe and Stoy, Andreas and B{\"o}hnke, Julian and Hofmann, Alexander and Bertermann, R{\"u}diger and Engels, Bernd and Braunschweig, Holger},
  title     = {Boranediyl- and Diborane(4)-1,2-diyl-Bridged Platinum A-Frame Complexes},
  series = {Chemistry - A European Journal},
  volume    = {26},
  journal   = {Chemistry - A European Journal},
  number    = {39},
  doi       = {10.1002/chem.202001168},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214707},
  pages     = {8518 -- 8523},
  year      = {2020},
  abstract  = {Diplatinum A-frame complexes with a bridging (di)boron unit in the apex position were synthesized in a single step by the double oxidative addition of dihalo(di)borane precursors at a bis(diphosphine)-bridged Pt\(^{0}\)\(_{2}\) complex. While structurally analogous to well-known μ-borylene complexes, in which delocalized dative three-center-two-electron M-B-M bonding prevails, theoretical investigations into the nature of Pt-B bonding in these A-frame complexes show them to be rare dimetalla(di)boranes displaying two electron-sharing Pt-B σ-bonds. This is experimentally reflected in the low kinetic stability of these compounds, which are prone to loss of the (di)boron bridgehead unit.},
  language  = {en}
}