Article
Chemistry, Multidisciplinary
Michael Reggelin, Stefan Immel
Summary: The study investigates the impact of vibrational analysis on the accuracy of back-calculating RDCs from molecular models, and the effects of thermal motions on the differentiability of diastereomers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Polymer Science
Timo Imhof, Jonas Kind, Christina M. Thiele
Summary: We studied the temperature-dependent LLC behavior of helically chiral polypeptides, specifically PBPMLG and PBLA-co-PPLA. We observed a characteristic jump in the quadrupolar splittings Delta nu Q of the solvent's 2H signal during the transition of polymer rods from perpendicular to parallel orientation with respect to the magnetic field. By correlating Delta nu Q with the diffusion coefficients measured parallelly (D parallel to) and perpendicularly (D perpendicular to) to the magnetic field, we found a significant change in the D parallel to/D perpendicular to ratio at the transition temperature of the LLC phases.
Article
Chemistry, Multidisciplinary
Sirine Nouri, Julien Boudet, Hiang Dreher-Teo, Frederic H. -T. Allain, Rudi Glockshuber, Loic Salmon, Christoph Giese
Summary: In NMR spectroscopy, residual dipolar couplings (RDCs) are highly accurate probes for investigating biological structure and dynamics. Type 1 pili, derived from bacteria, are introduced as an alternative liquid-crystalline alignment medium for measuring RDCs. By elongating wild-type pili, the medium is made suitable for efficient NMR sample preparation. Additionally, type 1 pili demonstrate compatibility with challenging experimental conditions, making them a valuable alternative to traditional alignment media in NMR studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Thirupathi Ravula, Edgar M. Faison, Marco Tonelli, Qi Zhang, Ayyalusamy Ramamoorthy
Summary: In this study, polymer-based nanodiscs were used to measure RDCs from nucleic acids. The nanodiscs were characterized and their alignment stability was confirmed. RDCs from a labeled nucleic acid molecule were successfully measured using the aligned nanodiscs. This demonstrates the potential of SMA-EA-based lipid-nanodiscs for structural and dynamical studies of nucleic acids.
Article
Chemistry, Multidisciplinary
Luca Venturi, Emanuela Bua, Giulia Caputo, Valentina Mileo
Summary: Residual dipolar couplings (RDCs) are a powerful tool in nuclear magnetic resonance (NMR) analysis for determining the structure of organic molecules. They are particularly valuable in the pharmaceutical industry for characterizing the stereochemistry of new chemical entities (NCEs) during the drug development process. In our study, RDCs were used to study the conformation and configuration of synthetic steroids with multiple stereocenters. We successfully identified the correct relative configuration for both prednisone and beclomethasone dipropionate (BDP), despite the large number of possible diastereoisomers.
Article
Chemistry, Multidisciplinary
Max Hirschmann, Olaf Soltwedel, Philipp Ritzert, Regine von Klitzing, Christina M. Thiele
Summary: Two polyaspartates, PpFABLA (1) and co-polyaspartate PpFABLA-co-PBLA [11, 75% (n/n) PpFABLA content], bearing ortho-fluorinated azo-benzenes (pFAB) as photo-responsive groups, undergo reversible coil-helix transition in solution through the E/Z-isomerization of the side chain. The thermal stability of the Z-isomer is increased by pFAB, and the helix formation is effectively prevented. The helical polymer forms a lyotropic liquid crystal (LLC) and orients unidirectionally inside a magnetic field, while the coil polymer results in an isotropic solution.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Max Hirschmann, Olaf Soltwedel, Philipp Ritzert, Regine von Klitzing, Christina M. Thiele
Summary: Two polyaspartates with ortho-fluorinated azo-benzenes (pFAB) as photo-responsive groups in the side chain were synthesized: PpFABLA (1) and co-polyaspartate PpFABLA-co-PBLA [11, 75%(n/n) PpFABLA content]. PpFABLA (1) undergoes a visible-light-induced reversible coil-helix transition in solution due to the E/Z-isomerization of the side chain. PpFABLA-co-PBLA (11) forms a helix independently of the E/Z-isomerization of the side chain and exhibits changes in the morphology and dipolar coupling.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Quantum Science & Technology
Thomas E. O'Brien, Lev B. Ioffe, Yuan Su, David Fushman, Hartmut Neven, Ryan Babbush, Vadim Smelyanskiy
Summary: We propose a quantum algorithm for inferring the molecular nuclear spin Hamiltonian from time-resolved measurements of spin-spin correlators. The algorithm can estimate the Hamiltonian parameters by directly learning the Jacobian and Hessian of the corresponding learning problem on a quantum computer, and computation on both noisy near-term and future fault-tolerant quantum computers can be performed. The research demonstrates the potential of quantum computations in interpreting and developing new NMR techniques for analyzing molecular structure.
Article
Chemistry, Multidisciplinary
Daiane S. Carvalho, Danilo G. B. da Silva, Fernando Hallwass, Armando Navarro-Vazquez
Summary: An NMR weakly-aligning polymer gel was prepared by copolymerization of acrylonitrile and 2-acrylamide-2-methyl-1-propanesulfonic acid with 1,4-butanediol diacrylate as a cross-linker. The gel swells in water over a wide range of temperatures, but its swelling ratio is reduced in saline solutions. The gel can undergo reversible mechanical compression, generating anisotropy, which is easily observed in H-2 NMR experiments and allows for measurement of D-1(CH) residual dipolar couplings (RDCs) through F1-coupled HSQC experiments. The gel's performance as an NMR alignment medium was evaluated for various water-soluble organic molecules, providing proper-sized RDCs for sucrose and even small molecules such as 5-norbornen-2-ol, but strong interaction between the gel and molecules like azidothymidine and cefuroxime sodium salt prevented successful extraction of RDCs.
Article
Chemistry, Multidisciplinary
Kathleen A. Farley, Martin R. M. Koos, Ye Che, Reto Horst, Chris Limberakis, Justin Bellenger, Ricardo Lira, Leandro F. Gil-Silva, Roberto R. Gil
Summary: This study presents a novel gel for aligning small organic molecules and cyclic peptides in water, which has been proven effective in molecular conformation analysis. The identification of minor conformers that cannot be easily determined by conventional methods will facilitate the use of RDC experiments in structure-based drug design.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Markus Zweckstetter
Summary: The AlphaFold2 method has shown the ability to accurately predict protein structures in solution, matching well with experimental data, and holds promise as a powerful tool for studying structural changes in proteins.
Article
Chemistry, Multidisciplinary
Niels Karschin, Stefan Becker, Christian Griesinger
Summary: This study presents a new approach using pseudocontact shifts and residual dipolar couplings to study protein interdomain motion. By sampling the conformational space and using a genetic algorithm, an accurate and reproducible model of the interdomain motion of Calmodulin/Munc13-1 was obtained without prior knowledge from crystallography.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Dominic S. Schirra, Philipp Goetz, Matthias Lehmann, Christina M. Thiele
Summary: Structure elucidation via residual dipolar couplings relies on alignment media. We report on lyotropic liquid crystals of poly-gamma-p-biphenyl(2'-methoxy-2-methyl)methyl-L-glutamate, which enables the acquisition of multiple RDC datasets within one sample.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Balabhadra Khatiwada, Trang T. Nguyen, Jeffrey A. Purslow, Vincenzo Venditti
Summary: This study investigates the structure and dynamics of human FTO protein in solution and reveals the instability of the catalytic N-terminal domain without the C-terminal domain. The study also demonstrates the conformational dynamics of the interface between FTO structural domains, active site, and peripheral loops. A conformational ensemble for apo FTO is generated, providing a potential target for the design of allosteric inhibitors.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Stefan Immel, Matthias Koeck, Michael Reggelin
Summary: This report introduces the floating chirality restrained distance geometry (fc-rDG) calculations for evolving structures from NMR data. Unlike evaluating pre-calculated structures, this method automatically generates multiple configurations within the experimental limits. The study also demonstrates the statistical significance of the unphysical rDG pseudo energies defined from NMR violations and their ability to assign probabilities to configurational assignments using Bayesian inference.
Article
Chemistry, Organic
Marketa Tichotova, Tomas Landovsky, Jan Lang, Sharon Jeziorowski, Volker Schmidts, Michal Kohout, Martin Babor, Pavel Lhotak, Christina M. Thiele, Hana Dvorakova
Summary: By using polyglutamates with different side-chain moieties (PBLG and PBPMLG) as alignment media, we achieved enantiodiscrimination of inherently chiral compounds for the first time. The experimental results not only provided more accurate structural information, but also revealed the conformational preferences and chiral alignment differences of phenoxathiin-based thiacalix[4]arenes in solution.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Tim Aguirre, Ellen Teichmann, Florian Q. Roempp, Ruthey Vivier, Cole Bryant, Matthew A. Hulverson, Wesley C. Van Voorhis, Kayode K. Ojo, J. Stone Doggett, Dorothea Fiedler, Stefan Hecht
Summary: This study developed photoswitchable azopyrazoles as inhibitors to selectively target CDPK1 from Toxoplasma gondii. The inhibitory activity of CDPK1 is dependent on the size of the gatekeeper residue. The photoswitchable inhibitors also showed activity against T. gondii and Cryptosporidium parvum infections in a cell culture model.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yu Zhou, Silvia P. Centeno, Kuan Zhang, Lifei Zheng, Robert Goestl, Andreas Herrmann
Summary: This study reports the development of a series of ratiometric optical force probes (OFPs) based on fluorescent-protein-dye and protein-protein conjugates, and their incorporation into genetically engineered bio-glues. The OFPs efficiently modulate Forster resonance energy transfer upon force application, reporting on force-induced molecular alterations independent of concentration and fluorescence intensity. By fluorescence spectroscopy in solution and in the solid state, as well as fluorescence lifetime imaging microscopy, stress concentrations are visualized and adhesive and cohesive failure in the fracture zone is differentiated.
ADVANCED MATERIALS
(2023)
Review
Chemistry, Multidisciplinary
Chung-Yang (Dennis) Huang, Stefan Hecht
Summary: This review explores the significance of indigo as a historical dye and its recent potential as a functional motif due to its intriguing photochemical properties. The synthesis of indigo core and available methods for derivatizing indigo are described, serving as synthetic strategies for building desired molecular structures. The photochemical behavior of indigos, particularly E-Z photoisomerization and photoinduced electron transfer, is discussed, emphasizing the connections between molecular structures and photochemical properties as guiding principles for designing indigos as photoresponsive tools.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Max Hirschmann, Olaf Soltwedel, Philipp Ritzert, Regine von Klitzing, Christina M. Thiele
Summary: Two polyaspartates, PpFABLA (1) and co-polyaspartate PpFABLA-co-PBLA [11, 75% (n/n) PpFABLA content], bearing ortho-fluorinated azo-benzenes (pFAB) as photo-responsive groups, undergo reversible coil-helix transition in solution through the E/Z-isomerization of the side chain. The thermal stability of the Z-isomer is increased by pFAB, and the helix formation is effectively prevented. The helical polymer forms a lyotropic liquid crystal (LLC) and orients unidirectionally inside a magnetic field, while the coil polymer results in an isotropic solution.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Polymer Science
Timo Imhof, Jonas Kind, Christina M. Thiele
Summary: We studied the temperature-dependent LLC behavior of helically chiral polypeptides, specifically PBPMLG and PBLA-co-PPLA. We observed a characteristic jump in the quadrupolar splittings Delta nu Q of the solvent's 2H signal during the transition of polymer rods from perpendicular to parallel orientation with respect to the magnetic field. By correlating Delta nu Q with the diffusion coefficients measured parallelly (D parallel to) and perpendicularly (D perpendicular to) to the magnetic field, we found a significant change in the D parallel to/D perpendicular to ratio at the transition temperature of the LLC phases.
Article
Multidisciplinary Sciences
Franziska Theiss, Laura Wienands, Jonas Lins, Marcel Alcaraz-Janssen, Christina M. Thiele, Gerd Buntkowsky
Summary: Nuclear magnetic resonance (NMR) experiments using parahydrogen-induced polarization (PHIP) were conducted to investigate the activity of the synthetic biopolymer poly-γ-(4-propargyloxy)-benzyl-L-glutamate) (PPOBLG). The homopolypeptide was successfully hyperpolarized and the enhanced signals were detected in 11.7 T solution NMR as a function of PPOBLG concentration. Hydrogenation with parahydrogen resulted in signal enhancements of over 800 times for the vinyl protons of the side chain at low substrate concentration. Due to the high enhancement factor, even at a concentration of 13 nM PPOBLG, the hyperpolarized protons could be detected with a single scan H-1-NMR, thanks to the combination of hyperpolarization and density of PHIP active sites.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Mingjun Xuan, Jilin Fan, Vu Ngoc Khiem, Miancheng Zou, Kai-Oliver Brenske, Ahmed Mourran, Rostislav Vinokur, Lifei Zheng, Mikhail Itskov, Robert Goestl, Andreas Herrmann
Summary: Polymer mechanochemistry is a promising technology to convert mechanical energy into chemical functionality by breaking bonds. In this study, a microbubble system was used to accelerate the mechanochemical activation of disulfides, and optimization conditions were identified.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Lucas Stuewe, Matthias Geiger, Franz Roellgen, Thorben Heinze, Marcus Reuter, Matthias Wessling, Stefan Hecht, John Linkhorst
Summary: This study advances the volumetric 3D printing technique xolography to a continuous process, enabling the continuous printing of objects with true shape and high resolution. By performing dual-color photopolymerization in a flowing resin within a specially designed flow cell, this technique offers the potential to scale up volumetric 3D printing and resolve the trade-off between high production rates and high resolution in light-based additive manufacturing.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Siyang He, Simon Schog, Ying Chen, Yuxin Ji, Sinan Panitz, Walter Richtering, Robert Goestl
Summary: The serial connection of multiple stimuli-responses in polymer architectures enables the gating of functional material processes on demand. In this study, a photoswitchable diarylethene is used as a crosslinker in poly(N-vinylcaprolactam) microgels to induce a shift in volume phase-transition temperature (VPTT). By switching the microgels from the swollen to the collapsed state using light, their response to mechanical force can be controlled. This photoinduced mechanical cloaking system operates on a polymer topology level and is universally applicable.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Filippo Giovanni Fabozzi, Nikolai Severin, Jurgen P. Rabe, Stefan Hecht
Summary: In this study, the on-surface polymerization of a vinylene-linked single-layer two-dimensional covalent organic framework using reversible Knoevenagel polycondensation under solvothermal conditions was described. The self-assembly of monomer building blocks at the solid-liquid interface led to the formation of extended covalent networks at room temperature without the need for additional catalysts or reagents. This approach provides a new pathway for the synthesis of extended conjugated 2D polymers under mild conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Johann J. Primozic, Julian Ilgen, Patrick Maibach, Matthias Brauser, Jonas Kind, Christina M. Thiele
Summary: The Pd-catalyzed allylic alkylation of 3,4-disubstituted, racemic cyclobutene electrophiles shows an unusual stereoselectivity. Stereoinduction is controlled by the choice of ligand and is independent of the substrate's configuration. Mechanistic investigations reveal deviations from the commonly accepted double inversion rule and the formation of unreactive syn-Pd-cyclobutene complexes due to strong internal Pd-O chelation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemical Research Methods
Ben Gerhardt, Kristin Klaue, Lennart Eigen, Jutta Schwarz, Stefan Hecht, Michael Brecht
Summary: Here, we introduce a X-ray-visible neural tracer called DiI-CT, which combines the well-known lipophilic indocarbocyanine dye DiI with two iodine atoms. This tracer is visible under microfocus computed tomography (microCT) imaging and retains the excellent tracing properties of DiI. We demonstrate the potential of DiI-CT in studying the vibrissa follicle-sinus complex, a structure with limited visual access and where 3D tissue structure is important, by revealing detailed innervation patterns. In the brain, DiI-CT tracing holds promise for validating indirect connectivity measures such as diffusion tensor imaging. In conclusion, the bimodal dye DiI-CT opens up new opportunities in neuroanatomy.
CELL REPORTS METHODS
(2023)
Article
Chemistry, Multidisciplinary
Kim Kuntze, Jani Viljakka, Matti Virkki, Chung-Yang (Dennis) Huang, Stefan Hecht, Arri Priimagi
Summary: By simple synthetic derivatisation, indigo dye can be converted into a red-light E-Z photoswitch, which exhibits negative photochromism and tuneable thermal isomerisation kinetics. This makes indigo derivatives highly attractive for materials and living systems applications. However, the translation of indigo photoswitching dynamics from solution to solid state, which is crucial for most applications, is not well understood. In this study, the photoswitching performance of six structurally distinct indigo derivatives in five polymers of varying rigidity is investigated. Three key strategies are identified to enable efficient photoswitching under red light: choosing a soft polymer matrix, creating free volume around the indigo molecules, and applying low dye loading to inhibit aggregation. Implementation of these strategies leads to isomerisation performance nearly identical to that in solution, paving the way for designing new red-light photochromic materials based on indigos.
