New Article in Organic Chemistry Frontiers
20 November 2023

Redox-induced Diels–Alder revisited: impact of diene’s oxidation on demanding cycloadditions

Michał J. Jadwiszczak, Piotr J. Leszczyński, Zoran Mazej, Przemysław J. Malinowski, Ewa K. Nawrocka,  Krzysztof Kazimierczuk, Piotr Kwiatkowski, Piotr Połczyński, Magdalena Grochowska-Tatarczak,a Karol J. Fijalkowski, Jarosław Sadło and Wojciech Grochala

Graphical abstract: Redox-induced Diels–Alder revisited: impact of diene's oxidation on demanding cycloadditions

This work presents the joint experimental and computational analysis of Diels–Alder (DA) reactions initiated by one-electron oxidation of dienes: anthracene and buta-1,3-diene derivatives. The use of AgSO4 – a very strong one-electron oxidizer – results in reactions proceeding via radical cationic intermediates rather than neutral species. In the case of anthracenes, yields of reactions are significantly enhanced compared to those for their neutral variants. Importantly, this includes also 9-halogenated anthracenes for which DA reactions reported in the literature are scarce. Surprisingly, diene oxidation has only a limited effect on derivatives of buta-1,3-diene. DFT modelling indicates that radical cations of dienes undergo DA reactions with dienophiles more readily than the corresponding neutral species. For anthracene derivatives, calculated barriers are in qualitative agreement with experimental findings. Careful analysis of the whole catalytic cycle allows us to point out various bottlenecks which are responsible for the poor performance of diene oxidation in reactions involving butadienes.

New Book Chapter

Data Processing Methods: Fourier and Beyond

Vladislav Orekhov, Paweł Kasprzak, Krzysztof Kazimierczuk

This chapter presents a compact overview of both practical and rigorously mathematical aspects of modern NMR signal processing. It discusses the properties of the Fourier transform (FT), which will be later useful to explain the effects of the experimental imperfections and signal processing procedures. The fast FT algorithm, used to calculate the discrete FT requires the same number of points in the input and output. However, one can increase the number of spectral points to any desired value by zero filling , that is, extending the free induction decay by adding artificial data points equal to zero at the end. The quadrature detection in one-dimensional spectra is realized through the acquisition of the two modulations, interpreted as real and imaginary parts of a complex NMR signal. The Projection Theorem is a powerful tool, useful in accelerating NMR experiments of dimensionality three and more.

New article in Magnetic Resonance in Chemistry

The assignment of 11B and 1H resonances in the post-reaction mixture from the dry synthesis of Li(BH3NH2BH2NH2BH3)

Ewa K. Nawrocka,  Agnieszka Prus, Rafał Owarzany, Wiktor Koźmiński, Krzysztof Kazimierczuk, Karol J. Fijalkowski

We report a detailed 1H NMR and 11B NMR study of as synthesised Li(BH3NH2BH2NH2BH3) obtained in a novel dry-synthesis method. A combination of 1D and 2D single- and triple quantum techniques was used for the assignment of all observed signals. Minor side-products and reactants were detected in the product: NH3BH3, Li(NH2BH3), Li(BH4) and two yet unknown salts containing 7-membered chain anions: (BH3NH2BH2NH2BH2NH2BH3)– and (BH(NH2BH3)_3)-. We believe the assignment provided within this study might be helpful when analysing the mixtures containing numerous ammonia borane derivatives which often give overlapping signals which are hard to distinguish.

New article in Journal of Magnetic Resonance Open
10 December 2022

Radon peak-picker based on a neural network

Ewa K. Nawrocka,  Daniel Dahan, Krzysztof Kazimierczuk, Przemysław Olbratowski

Serial acquisition of one-dimensional NMR spectra appears in many contexts, e.g. in variable-temperature studies or reaction monitoring. In a conventional approach, the spectra are processed separately, and standard peak-picking is performed in each of them. Yet, when chemical shifts change linearly between spectra, the Radon transform (RT) is more effective than conventional data processing, since it provides sensitivity and resolution gains. RT results in a two-dimensional (2D) spectrum with one dimension corresponding to resonance frequencies and the other to their rates of change. However, the lineshapes in 2D RT spectra are not 2D lorentzians, and thus available spectral peak-pickers cannot effectively deal with them. We propose a solution to this problem — a peak-picker dedicated to 2D RT spectra and based on a U-Net neural network. The software contains a user-friendly graphical interface. We test the program on three challenging serial data sets to demonstrate the robustness to peak overlap, complex multiplet structures and low signal-to-noise ratio.

New article in PLOS Computational Biology
03 November 2022

Linear discriminant analysis reveals hidden patterns in NMR chemical shifts of intrinsically disordered proteins

 Javier A. Romero, Paulina Putko, Mateusz Urbańczyk, Krzysztof Kazimierczuk, Anna Zawadzka-Kazimierczuk

NMR spectroscopy is key in the study of intrinsically disordered proteins (IDPs). Yet, even the first step in such an analysis—the assignment of observed resonances to particular nuclei—is often problematic due to low peak dispersion in the spectra of IDPs. We show that the assignment process can be aided by finding “hidden” chemical shift patterns specific to the amino acid residue types. We find such patterns in the training data from the Biological Magnetic Resonance Bank using linear discriminant analysis, and then use them to classify spin systems in an α-synuclein sample prepared by us. We describe two situations in which the procedure can greatly facilitate the analysis of NMR spectra. The first involves the mapping of spin systems chains onto the protein sequence, which is part of the assignment procedure—a prerequisite for any NMR-based protein analysis. In the second, the method supports assignment transfer between similar samples. We conducted experiments to demonstrate these cases, and both times the majority of spin systems could be unambiguously assigned to the correct residue types.

New Article in Analytical Chemistry

Enhanced Nuclear Magnetic Resonance Spectroscopy with Isotropic Mixing as a Pseudodimension

Dariusz Gołowicz, Alexandra Shchukina, Krzysztof Kazimierczuk

Chemical analysis based on liquid-state nuclear magnetic resonance spectroscopy exploits numerous observables, mainly chemical shifts, relaxation rates, and internuclear coupling constants. Regarding the latter, the efficiencies of internuclear coherence transfers may be encoded in spectral peak intensities. The dependencies of these intensities on the experimental parameter that influences the transfer, for example, mixing time, are an important source of structural information. Yet, they are costly to measure and difficult to analyze. Here, we show that peak intensity build-up curves in two-dimensional total correlation spectroscopy (2D TOCSY) experiments may be quickly measured by employing nonuniform sampling and that their analysis can be effective if supported by quantum mechanical calculations. Thus, such curves can be used to form a new, third pseudodimension of the TOCSY spectrum. Similarly to the other two frequency dimensions, this one also resolves ambiguities and provides characteristic information. We show how the approach supports the analysis of a fragment of protein Tau Repeat-4 domain. Yet, its potential applications are far broader, including the analysis of complex mixtures or other polymers.