Information provided here must correspond accurately with information provided in the dataset metadata record, e.g. the dataset title should match exactly, the same Creators should be listed, etc. 1. ABOUT THE DATASET -------------------- Title: In Situ Dynamics of the Microscopic Crystallographic Dehydration Pathway in Theophylline a Model Channel Hydrate Creator(s): Natalia Koniuch[1,2], Sang T. Pham[1,2], Mohsen Danaie[3], Fanny Costa[2], Zabeada Aslam[2], Stephanie Foster[1,2], Helen Blade[4], Leslie Hughes[4], Nicole Hondow[1,2], Rik Drummond-Brydson[1,2], Sean M. Collins[1,2,5,6] and Andrew P. Brown[1,2] Organisation(s):[1] School of Chemical and Process Engineering, University of Leeds, UK [2] Bragg Centre for Materials Research, University of Leeds, UK [3] Electron Physical Science Imaging Centre (ePSIC), Diamond Light Source, Didcot, UK [4] AstraZeneca, Oral Product Development, Pharmaceutical Technology & Development, Operations, Macclesfield, UK [5] School of Chemistry, University of Leeds, UK [6] Department of Materials, Royal School of Mines, Imperial College London, UK Rights-holder(s): Unless otherwise stated, Copyright 2026 University of Leeds Publication Year: 2026 Description: This dataset contains original low-dose scanning electron diffraction (SED) data acquired during in situ vacuum and heating dehydration experiments on theophylline monohydrate, associated calibration datasets, transmission electron microscopy (TEM) data from initial in situ heating experiments, and powder X-ray diffraction (pXRD) data with crystallographic refinement files. The data support the investigation of crystallographic and morphological changes during dehydration of theophylline monohydrate and its transformation to anhydrous form II. Experimental data and associated analysis files are provided in their original formats. Cite as: Koniuch, Natalia; Pham, Sang T.; Danaie, Mohsen; Costa, Fanny; Aslam, Zabeada; Foster, Stephanie; Blade, Helen; Hughes, Leslie; Hondow, Nicole; Drummond-Brydson, Rik; Collins, Sean M.; and Brown, Andrew P. (2026): Dataset for 'In Situ Dynamics of the Microscopic Crystallographic Dehydration Pathway in Theophylline a Model Channel Hydrate'. University of Leeds. [Dataset] https://doi.org/10.5518/1946 Related publication: Natalia Koniuch, Sang T. Pham, Mohsen Danaie, Fanny Costa, Zabeada Aslam, Stephanie Foster, Helen Blade, Leslie Hughes, Nicole Hondow, Rik Drummond-Brydson, Sean M. Collins and Andrew P. Brown, In Situ Dynamics of the Microscopic Crystallographic Dehydration Pathway in Theophylline a Model Channel Hydrate, Communications Chemistry, 2026. Status at time of dataset deposit: under revision following peer review Preprint available at: arXiv:2606.12029 Contact: N.A.Koniuch@leeds.ac.uk, S.M.Collins@imperial.ac.uk, A.P.Brown@leeds.ac.uk 2. TERMS OF USE --------------- Copyright [2026] [University of Leeds, Diamond Light Source, AstraZeneca, Imperial College London]. Unless otherwise stated, this dataset is licensed under a Creative Commons Attribution 4.0 International Licence: https://creativecommons.org/licenses/by/4.0/. 3. PROJECT AND FUNDING INFORMATION ---------------------------------- Title: Ultramicroscopy of complex materials - IDPC STEM Dates: January 2019 - May 2024 Funding organisation: iCASE studentship (AstraZeneca Ltd and the Engineering and Physical Sciences Research Council (EPSRC)), the EPSRC, Diamond Light Source - Rutherford Appleton Laboratory (UK), and the University of Leeds Grant no.: 2182593; EP/X040992/1; MG28500; MG30057; and MG39047 4. CONTENTS ----------- File listing SED in situ 1 - vacuum dehydration.zip: Raw low-dose scanning electron diffraction (SED) datasets of theophylline monohydrate acquired during in situ vacuum dehydration experiments at room temperature. Data are organised into four subfolders (area 1-4), corresponding to different regions of interest. Each area contains two subfolders (1_initial and 2_after), with measurements collected immediately after loading and after approximately 17 h under vacuum, respectively. SED in situ 2 - heating dehydration.zip: Raw low-dose SED datasets of theophylline monohydrate acquired during in situ heating dehydration experiments. Data are organised into subfolders according to the acquisition temperature (room temp, 65C, 85C and 100C), with each folder containing an individual SED dataset. Both SED archives contain a calibration data folder with Au_xgrating and MoO3 reference datasets, used for scan pixel size calibration, correction of diffraction pattern distortions and determination of scan-pattern rotation. The SED and calibration datasets are saved in HDF5 format, compatible with HyperSpy and pyXem, open-source Python packages for multidimensional electron microscopy data analysis. Individual datasets retain their original acquisition filenames, indicating the date and time of acquisition (YYYYMMDD_HHMMSS). TEM in situ heating.zip: Bright-field TEM images and selected-area electron diffraction (SAED) patterns acquired during initial in situ heating experiments on theophylline monohydrate. Data are saved in DM3 format and can be opened using Gatan DigitalMicrograph or HyperSpy. Filenames indicate the region of interest (a1, a2, etc.), imaging mode (BF or SAED) and acquisition temperature in °C. XRD.zip: Experimental powder X-ray diffraction (pXRD) data of theophylline monohydrate saved in Excel (.xlsx) format, together with Rietveld refinement files for the THEOPH01 (P21/n) and THEOPH08 (P21) structural models. Refinements were performed using TOPAS Academic v.7. Crystallographic information (.cif), refinement input (.inp) and output (.out) files are provided for each structural model. README.txt: Description of the deposited datasets, folder structure, experimental methods, file formats and software used for data analysis. 5. METHODS ---------- Sample preparation: Theophylline monohydrate was prepared by evaporative recrystallisation of anhydrous form II (Sigma-Aldrich, >99% purity) from an ethanol-water mixture (3:2 molar ratio). The solution was heated to approximately 55 C and cooled gradually to ~35 C under continuous stirring. Upon initial precipitation, a drop was deposited onto holey carbon TEM grids (EM Resolutions) or DENSsolutions Wildfire Nano-Chips with amorphous Si3N4 support films. Samples were stored at 93% relative humidity, maintained using a saturated potassium nitrate (KNO3) solution, to preserve the hydrate phase. Powder X-ray diffraction: The pXRD pattern of recrystallised theophylline monohydrate was collected using a Bruker D8 Advance diffractometer with Cu Kα radiation (λ = 1.54180 Å). Data were collected at a scanning speed of 0.5 s per 0.02° step over a 2θ range of 5-40°. Rietveld refinements were performed using TOPAS Academic v.7, employing the fundamental-parameter approach for peak-profile modelling. Two crystal structures of theophylline monohydrate, THEOPH01 (P21/n, CCDC 183780) and THEOPH08 (P21, CCDC 2264675), were used as structural models to fit the experimental data. Transmission electron microscopy: Initial TEM characterisation was performed using an FEI Titan3 Themis microscope operated at 300 kV at the University of Leeds. Bright-field TEM images and selected-area electron diffraction (SAED) patterns were acquired under low-dose conditions, using an electron flux of 0.08–0.09 e- Å-2 s-1. In situ TEM heating experiments were performed using a Gatan single-tilt heating holder (model 628). Scanning electron diffraction: Low-dose SED datasets were collected on a JEOL ARM300CF operated at 300 kV at the electron Physical Sciences Imaging Centre (ePSIC), Diamond Light Source (UK). A 10 um condenser aperture was used to produce a convergence semi-angle below 1 mrad, corresponding to a diffraction-limited probe of ~5 nm diameter. The probe current was set to 1 pA, and the exposure time was 1 ms per probe position, giving an estimated electron fluence of ~8 e- Å-2 per diffraction pattern. Diffraction patterns were recorded using a Merlin-Medipix hybrid counting direct electron detector (Quantum Detectors, UK). The beam was rastered with a step size of 7.8 nm over a 256 x 256 pixel scan. For in situ vacuum dehydration, regions of interest were scanned immediately after loading and then again after ~17 h in the TEM vacuum. For in situ heating dehydration, SED data were acquired using a DENSsolutions Wildfire heating holder at room temperature, 65 °C, 85 °C and 100 °C. Calibration and data analysis: Calibration was performed using standard MoO3 and Au cross-grating samples to correct scan-pattern rotation, calibrate pixel size and remove elliptical distortions. TEM images and SAED patterns were processed using DigitalMicrograph (Gatan Microscopy Suite) and ImageJ. SED datasets were analysed using HyperSpy (v.1.6.5 and 1.7.5) and pyXem (v.0.11.0 and 0.13.0), including direct-beam alignment, diffraction pattern calibration and generation of average diffraction patterns and virtual dark-field (VDF) images. Crystallographic analysis and diffraction simulations were performed using CrystalMaker, CCDC Mercury and VESTA. The repository contains raw, unbinned SED datasets, associated calibration data, TEM images and pXRD data with Rietveld refinement files. Full experimental details and analysis methods are described in the associated manuscript: Koniuch et al., 'In Situ Dynamics of the Microscopic Crystallographic Dehydration Pathway in Theophylline a Model Channel Hydrate', Communications Chemistry (under revision at the time of deposit).