Magic size oxo-cluster formation from Crystallography beyond the crystal

mechanochemically synthesized Total scattering measurements of neutrons or synchrotron radiation, together

with pair distribution function (PDF) analysis, are a powerful tool for structural
precursor analysis of local, molecular structure. It can be used not only for solids, but also
for liquid samples[4]. Transforming total scattering data with Fourier transform,
Daniel M. Szczerba1, Tomislav Friščić2, Simon A. J. yields a plot representing real-space. That stands in a contrast to the reciprocal
Kimber 1
space of PXRD, therefore enabling new ways of data analysis [5].
1
Université Bourgogne Franche-Comté – 9 avenue Alain Savary, Bâtiment Sciences Mirande, 21000 Dijon, France For the bismuth subsalicylate, the PDF
2
McGill University – Department of Chemistry, 801 Sherbrooke St. West, Montréal, Québec H3A 0B8
analysis shows that the cluster size
depends on the type solvent and time
Introduction (Fig. 5). Some solvents result in
Some bismuth-organic chemical compounds show a tendency to form large metal obtaining [Bi38O45] cluster, whereas
oxo-clusters. Some of such compounds are used to treat bacterial infections, others favor a smaller, [Bi9O7] cluster.
particularly with Helicobacter Pylori, and some digestive problems [1]. Recently it The growth of clusters is expected to
was even shown that bismuth APIs (active pharmaceutical ingredients) could be be gradual, therefore other, unstable
beneficial in treating patients after Covid-19 [2]. Here we report the synthesis of species are most certainly also present
polymeric precursors by mechanochemistry, and a solvolysis process leading to in solution.
forming a [Bi38O45] oxo-cluster, along with PDF of total scattering data analysis
Fig. 4. C60 fullerene can be an example of the
power of PDF as an analysis method. The PXRD
Mechanochemical precursor synthesis pattern (left, upper graph) does not provide much
The use of mechanosynthesis has some advantages. Full conversion of bismuth structural information, since the molecules in the
crystal structure are constantly rotating. The PDF
(III) disalicylate can be achieved (Fig. 2a) using simple precursors, and the model however (left, lower graph), shows the
reactions proceed without bulk solvent. Furthermore, the reaction is reproducible, distances between atoms, and the size of the C60
and could be scaled to a large scale process. clusters.

Fig. 1. Reaction scheme.

From reference [1].

ILAG acetone
Bi2 O 3 + HSal → →

Pure bismuth (III) disalicylate was synthesized using ILAG (ion and liquid-assisted
grinding) method[3] that was improved over the previously reported. That enabled
discovering possibility of performing bismuth subgallate (Fig. 2b) and other
bismuth APIs synthesis using the same, mechanochemical method.

Fig. 5. PDF patterns of bismuth (III) disalicylate in

solutions. On the right the influence of solvents
becomes apparent. Red circle indicates peaks
Fig. 2a. Rietveld refinement of present in pentanone and aged DMF (with higher
bismuth (III) disalicylate structure water content) solutions, which are absent in fresh
in a sample synthesized using acetone, cyclohexanone etc. With aging of the
ILAG. solution (above), the larger cluster appears.

Symmetry analysis
The inner structure of an isolated [Bi38O45] cluster is very interesting in terms of
its symmetry. The core is made of an octahedra surrounded by a cube and an
Fig. 2b. Rietveld refinement of
icosahedra. This type of a structure is called keplerate. Solid-state data shows
bismuth (III) subgallate structure that the bismuth atoms are displaced from perfect keplerate positions. However,
in a sample with traces bismuth simulated cluster core, with perfect bismuth positions, is matching the PDF of
(III) oxide, synthesized using
ILAG.
liquid samples better. We are currently investigating symmetry adapted mode
approaches to understand this, and the influence of crystallization, ligands etc.
on the core structure.

UV-Vis spectrometry
The growth of the clusters takes place in solution[3]. Bismuth disalicylate dispersed
in acetone, DMF or other organic solvent undergoes a solvolysis process, forming
various species of bismuth oxo-clusters. [Bi 38O45] is thought to be the most stable of Fig. 6. Fit of the distorted [Bi38O45] cluster structure
them, and after a certain time nucleation of it causes formation of vividly red seen as PDF to a plot calculated on perfect keplerate. Fig. 7. The distortions produced by a
The bismuth positions displacements were produced single symmetry adapted parameter
crystals. The presence of different sizes of clusters is visible in changes of UV-Vis with a single symmetry adapted parameter. shown in the form of vectors on a model.
spectra in time, as well as the PDF data.
Fig. 3. UV-Vis spectrum of bismuth clusters
in acetone, compared with salicylic acid
Conclusion
acetone solution, next to a picture of the Mechanosynthesis of bismuth APIs is a new, clean way of synthesizing
measured sample. The color of presented common metallodrugs. Their chemical reactions in solution are a compelling
sample agrees with the spectrum, showing
particular UV-Vis peak of the [Bi38O45] target for PDF analysis due to the variety of structures and their interesting
cluster. The highest point is at 460 nm. The symmetry. [Bi38O45] oxo-cluster and its “ordered” distortion broaden our
shape of peak suggests presence of multiple, understanding of the difference in behavior of molecules surrounded by ligands
absorbing species in the solution, and so
does the change in highest point going from in solution and in the solid state, and therefore are an interesting subject for
higher to lower wavelength. further analysis. contact: daniel_szczerba@etu.u-
bourgogne.fr

[1] Malferheiner, P., Nilius, M. and Kreusel, U. (1994), “Bismuth and Helicobacter pylori”. Springer Berlin Heidelberg. p. 266-279;
[2] Yuan, S. Et al. (2020), “Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters”. Nature Microbiology, Vol. 5, Issue 11, p. 1439-1448;
[3] André, V., Hardeman, A., Halasz, I., Stein, R. S., Jackson, G. J., Reid, D. G., Duer, M. J., Curfs, C., Duarte, M. T. and Friščić, T. (2011), “ Mechanosynthesis of the Metallodrug Bismuth Subsalicylate from Bi 2O3 and Structure of Bismuth Salicylate without Auxiliary Organic Ligands”. Angew. Chem. Int. Ed., 50:
7858-7861;
[4] Zobel, M., Neder, R. B., Kimber, S. A. J. (2015), “Universal solvent restructuring induced by colloidal nanoparticles“. Science Vol. 357, issue 6219: 292-294.
[5] Egami, T. and Billinge, S. (2012), “Underneath the Bragg Peaks”. Elsevier, Pergamon Materials Series Wevol. 16.
acknowledge the I-SITE BFC and UBFC program for funding the research, the interfaces group of ICB
laboratory for hosting and members of.Tomislav Friščić group for cooperation.