Materials design for wider organic electronics greatly benefits from supramolecular chemistry approaches, whereby elucidating structure-driven noncovalent interactions across length scales represents a characterization challenge. Methods probing long-range order often struggle to identify the heterogeneous nature of van der Waals interactions, leaving locally disordered regions and their impact on bulk properties unexamined. This study demonstrates that structural polymorphism in regioisomeric pyridine-substituted naphthalene diimide (PyNDI) assemblies imparts varying degrees of order and disorder. A synergistic combination of X-ray diffraction (XRD) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy, supported by computational modeling, reveals that supramolecular order in ortho (o)- and para (p)-PyNDIs arises from cooperative pi-stacking, lone-pair-pi interactions, and lamellar interdigitation. In contrast, the meta (m)-isomer exhibits local disorder with different packing motifs that can be iteratively modeled using the structural knowledge obtained from their o- and p-PyNDIs crystalline analogues. The approach uniquely resolves locally disordered motifs by leveraging information obtained from structurally similar, but well-ordered, isomers of pi-conjugated assemblies relevant to the optoelectronic paradigm.

This paper presents a new molecular dynamics system observable in steroidal selenides. The system was investigated using a pair of epimeric selenosteroids derived from the naturally occurring compound hecogenin. These two compounds differ solely in configuration at the C12 stereogenic center and were selected as a model system to probe local motional averaging in the solid state. Comprehensive structural and spectroscopic characterisation was carried out using solid-state CP/MAS NMR spectroscopy, X-ray crystallography, and variable-temperature electron-capture detection (ECD) spectroscopy. Despite minimal structural variation, the epimers exhibited evidence of motional averaging in the solid state, suggesting that local stereochemistry may influence intramolecular motion. These findings demonstrate that selenosteroids, which combine a rigid steroidal stator with a selenium-based rotator, constitute a promising platform for investigating molecular dynamics and may enable the development of a new class of functional materials.

Metal halide perovskites (MHPs) are versatile semiconductors with high defect tolerance. Among emerging MHP architectures, the 3D "hollow" perovskites incorporating ethylenediammonium (en) dications represent a unique defect-stabilization paradigm by retaining structural order, stability, and performance. But the local chemical environments of defects that underpin bulk properties have remained unresolved, due to the inherently averaging nature of diffraction techniques. Here, we address this information gap by probing both crystallinity and defect-specific local structures in three representative hollow systems: enMAPbI 3 , enFAPbI 3 , and enFAPbBr 3 (MA: methylammonium; FA: formamidinium) using powder X-ray diffraction (PXRD), periodic density-functional theory (DFT), and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. Specifically, ssNMR allows to identify and quantify two distinct vacancy regimes: a low-en (below 30%) regime with predominantly trans en conformers that stabilize the framework by simultaneously generating Pb vacancies; and a new high-en (above 30%) regime where conformationally tilted en dications lead to distortions in PbX6 octahedra and crystallinity features. Modulated by the non-covalent interactions, insights into defect sites can be obtained by analyzing 1D 1 H, 207 Pb, and 2D 1 H- 1 H and 1 H- 14 N correlation NMR spectra acquired at a high magnetic field (21 T) with fast magic-angle spinning (MAS). These findings help explain defect compensation mechanisms, reconciling correlated trends between bandgap evolution and stability across iodine-and bromine-based hollow perovskites. In addition, they provide a framework for rationalizing defectengineering strategies in hybrid perovskites and related metal halides.

Functional macromolecular materials promise to enable important improvements in many aspects of everyday life, including for energy applications, novel electronics systems, or wearable health care products. In contrast to widely-used commodity plastics such as polyolefins, polyamides, or polyesters, it, however, remains challenging to advance detailed insights into the interrelation of structure and performance for functional polymers, limiting progress. The reason is that the macroscopic properties of such polymers often depend on local chain arrangements rather than long-range order only. Here, it is demonstrated on the example of the well-investigated ferroelectric poly(vinylidene fluoride) (PVDF) that modern nuclear magnetic resonance (NMR) spectroscopy enables the quantitative analysis of the complex solid-state structure of this polymer, providing unprecedented insight. The precise fractions of chain segments of different conformations are revealed, as well as their spatial distributions with respect to each other. Thereby, a significant population of short-range ordered chain segments is identified, a large fraction of which in close proximity to defects and disordered segments. Unsurprisingly, different environments lead to different structural dynamics - collectively showing that characterizing local order/disorder and their dynamics is imperative to accurately describe the properties of functional polymers such as PVDF.

We present the application of the oxathiaphospholane method for the synthesis of novel P-stereodefined phosphorothioate N-modified morpholino analogs, showcasing its potential for creating therapeutically relevant compounds. Additionally, we provide valuable structural insights into their stereochemistry, including a detailed analysis of stereochemical configurations. We also report on the enzymatic stability of these compounds in 10% (v/v) fetal bovine serum (FBS), thereby mimicking in vivo conditions. These findings pave the way for further exploration of P-stereodefined nucleic acid analogs in molecular medicine and gene therapy applications.

A cross-polarization 2H-1H isotope correlation spectroscopy (CP-iCOSY) approach is presented for characterizing a deuterated amino acid, pharmaceutical compound and a solid formulation. This can be achieved by isotopic enrichment in conjunction with high magnetic field (28.2 T) and fast magic-angle spinning (MAS), enabling the rapid detection of 2H NMR spectra in a few seconds to minutes. Specifically, two-dimensional (2D) 2H-1H CPiCOSY experiment allows the local structures and through-space interactions in a partially deuterated compounds to be elucidated. In doing so, we compare conventional spin-lock and rotor-echo-short-pulse-irradiation RESPIRATIONCP sequences for acquiring 2D 1H-2H correlation spectra. The RESPIRATIONCP sequence allows the detection of 2D peaks at lower CP contact times (0.1-1 ms) than the conventional CP (0.2-4 ms) sequence. Analysis of partially deuterated L-histidine center dot HCl center dot H2O and dopamine.HCl is presented, in which the detection of 2D peaks corresponding to 2H-1H pairs separated by greater than 4 & Aring; distance demonstrates the potential of the presented approach for the characterization of packing interactions. These results are corroborated by NMR crystallography analysis using the Gauge-Including Projector Augmented-Wave (GIPAW) approach.

Understanding and mitigating performance variability are important for developing organic photovoltaics (OPVs), which are often governed by solid-state organization of molecular entities in semiconductor thin films. This is why achieving structural resolution is essential. This study demonstrates how often-hidden structural polymorphism profoundly influences the power conversion efficiency (PCE) of bulk heterojunction (BHJ) OPVs. The devices consisting of PM6:Y6 BHJ layers cast from low-boiling chloroform (CF; PCE approximate to 15%) and high-boiling o-xylene solvents (o-XY; PCE approximate to 10%) exhibit morphology-dependent optical absorption, charge transport, and recombination dynamics. A synergistic multimodal characterization combined with device physics reveals that the retention of solvents and additives leads to polymorphous BHJ layers, contributing to performance variation. These results strengthen the conclusion that green solvent selection should be guided not only by environmental considerations but also by a thorough understanding of structure-property interrelations, which are vital for improving material performance in OPVs.

This paper presents structural and biological studies of two cyclic oligopeptides obtained as a result of macrocyclization of linear precursors containing the same amino acid composition, but arranged in reverse order. The first of them with an amino acid sequence (G1D2A3Y4A5Q6W7L8A9D10G11G12P13S14S15G16R17P18P19P20S21G22-) belongs to a group of oligopeptides known in the literature as Tryptophan Cage (Trp_C), often used as models to test and understand the mechanism of protein folding. The knowledge about second precursor (-G1S2P3P4P5R6G7S8S9P10G11G12D13A14L15W16Q17A18 Y19A20D21G22-) is not so extensive. The cyclic forms of both compounds labeled as cTrp_C and Inv-cTrp_C were studied by mass spectrometry (ESI MS and ESI MS/MS), electronic circular dichroism (ECD) and 1D and 2D NMR spectroscopy. ECD and NMR measurements were performed in a different solvents and a wide temperature range. The experimental data clearly demonstrated differences in thermal stability and conformational changes for the two samples. The nature and mechanism of these changes were investigated by means of Molecular Dynamics calculations. Theoretical studies have shown that for cTrp_C and Inv-cTrp_C the length and structure of the -helix, which is the core stabilizing the geometry of cyclic oligopeptides, are different. In the case of Inv-cTrp_C, two edge models with a indole ring of tryptophan (W16) inside the cage (Inv-cTrp_C1) and outside the cage (Inv-cTrp_C2) are postulated. Based on theoretical calculations, it is speculated that the formation of these two structures is due to the large-amplitude reorientation of the unstructured chain around the -helix.

The Front Cover shows a polymeric network with molecular rotors (MR) as crosslinks. The MR rotation is slowed or inhibited when a molecule of stored gas is placed inside the polymer material. More information can be found in the Research Article by Izabella Jastrzebska and co-workers.

The front cover artwork is provided by Dr habil. Izabella Jastrzebska's group from the University of Białystok, Poland. The image shows a polymeric network with molecular rotors (MR) as crosslinks. The MR rotation is slowed or inhibited when a molecule of stored gas is placed inside the polymer material. Read the full text of the Research Article at 10.1002/cphc.202300793.

Cyclic tetrapeptides c(Pro-Phe-Pro-Phe) obtained by the mechanosynthetic method using a ball mill were isolated in a pure stereochemical form as a homochiral system (all L-amino acids, sample A) and as a heterochiral system with D configuration at one of the stereogenic centers of Phe (sample B). The structure and stereochemistry of both samples were determined by X-ray diffraction studies of single crystals. In DMSO and acetonitrile, sample A exists as an equimolar mixture of two conformers, while only one is monitored for sample B. The conformational space and energetic preferences for possible conformers were calculated using DFT methods. The distinctly different conformational flexibility of the two samples was experimentally proven by Variable Temperature (VT) and 2D EXSY NMR measurements. Both samples were docked to histone deacetylase HDAC8. Cytotoxic studies proved that none of the tested cyclic peptide is toxic.

The applicability of different solvent-free approaches leading to the amorphization of active pharmaceutical ingredients (APIs) was tested. Ethenzamide (ET), an analgesic and anti-inflammatory drug, and two ethenzamide cocrystals with glutaric acid (GLU) and ethyl malonic acid (EMA) as coformers were used as pharmaceutical models. Calcinated and thermally untreated silica gel was applied as an amorphous reagent. Three methods were used to prepare the samples: manual physical mixing, melting, and grinding in a ball mill. The ET:GLU and ET:EMA cocrystals forming low-melting eutectic phases were selected as the best candidates for testing amorphization by thermal treatment. The progress and degree of amorphousness were determined using instrumental techniques: solid-state NMR spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. In each case, the API amorphization was complete and the process was irreversible. A comparative analysis of the dissolution profiles showed that the dissolution kinetics for each sample are significantly different. The nature and mechanism of this distinction are discussed.

Three new crystal structures of 1H-benzo[d]imidazole derivatives were determined. In the structures of these compounds, an identical system of hydrogen bonds, C(4), was observed. Solid-state NMR was applied for testing the quality of the obtained samples. All of these compounds were tested for in vitro antibacterial activity against Gram-positive bacteria and Gram-negative bacteria, as well as antifungal activity, by checking their selectivity. ADME calculations indicate that the compounds can be tested as potential drugs.

Analysis of short-to-intermediate range intermolecular interactions offers a great way of characterizing the solidstate organization of small molecules and materials. This can be achieved by two-dimensional (2D) homo- and heteronuclear correlation NMR spectroscopy, for example, by carrying out experiments at high magnetic fields in conjunction with fast magic-angle spinning (MAS) techniques. But, detecting 2D peaks for heteronuclear dipolar coupled spin pairs separated by greater than 3 ?, is not always straightforward, particularly when low-gamma quadrupolar nuclei are involved. Here, we present a 2D correlation NMR experiment that combines the advantages of heteronuclear-multiple quantum coherence (HMQC) and proton-based spin-diffusion (SD) pulse sequences using radio-frequency-driven-recouping (RFDR) to probe inter and intramolecular 1H-X (X = 14N, 35Cl) interactions. This experiment can be used to acquire 2D 1H{X}-HMQC filtered 1H-1H correlation as well as 2D 1H-X HMQC spectra. Powder forms of dopamine center dot HCl and L-histidine center dot HCl center dot H2O are characterized at high fields (21.1 T and 18.8 T) with fast MAS (60 kHz) using the 2D HMQC-SD-RFDR approach. Solid-state NMR results are complemented with NMR crystallography analyses using the gauge-including projector augmented wave (GIPAW) approach. For histidine center dot HCl center dot H2O, 2D peaks associated with 14N-1H-1H and 35Cl-1H-1H distances of up to 4.4 and 3.9 ?, have been detected. This is further corroborated by the observation of 2D peaks corresponding to 14N-1H-1H and 35Cl-1H-1H distances of up to 4.2 and 3.7 ?, in dopamine center dot HCl, indicating the suitability of the HMQC-SD-RFDR experiments for detecting medium-range proximities in molecular solids.

Tuberculosis remains one of the most common diseases affecting developing countries due to difficult living conditions, the rapidly increasing resistance of M. tuberculosis strains and the small number of effective anti-tuberculosis drugs. This study concerns the relationship between molecular structure observed in a solid-state by X-ray diffraction and the 15N NMR of a group of pyridine derivatives, from which promising activity against M. tuberculosis was reported earlier. It was found that the compounds exist in two tautomeric forms: neutral and zwitterionic. The latter form forced the molecules to adopt a stable, unique, flat frame due to conjugation and the intramolecular hydrogen bond system. As the compounds exist in a zwitterionic form in the crystal state generally showing higher activity against tuberculosis, it may indicate that this geometry of molecules is the “active” form.

The solid-state organization of photoabsorber, hole and electron transporting layers, and interfaces between them plays an important role in governing the performance and stability of emerging optoelectronic devices such as perovskite solar cells (PSCs). The molecular organic semiconductor (OSC) 2,2′,7,7′-tetrakis [N,N-di(4-methoxyphenyl)amino]-9,9′-spirobifluorene (spiroOMeTAD) is a promising hole-transporting material (HTM) for PSCs, which is p-doped by molecular dopants to augment the charge carrier mobility. Here, the p-type doping of spiroOMeTAD by tris(pentafluorophenyl)borane (BCF) is investigated by a combination of techniques including optical spectroscopy, X-ray diffraction, Fourier transform infrared (FTIR), solid-state (ss)NMR, and electron paramagnetic resonance (EPR) spectroscopy. BCF molecules interact with traces of water molecules to form BCF-water complexes. Optical spectroscopy analysis suggests that the BCF/BCF-water complexes oxidize spiroOMeTAD molecules and facilitate p-type doping of spiroOMeTAD molecules. The different distributions of BCF and BCF-water molecules in doped spiroOMeTAD are characterized by FTIR and 11B NMR spectroscopy. An NMR crystallography approach which combines two-dimensional (2D) ssNMR and crystallography modeling is employed to unravel the packing interactions in spiroOMeTAD, and this analysis is extended to probe the morphological and structural changes in spiroOMeTAD:BCF blends. The hyperfine interactions are characterized by 2D hyperfine sub-level correlation (HYSCORE) spectroscopy. In this way, insight into the complex spiroOMeTAD:BCF blend morphology is obtained and compared for different dopant concentrations. Molecular-level analysis of doped HTMs enabled by this study has much wider relevance for further investigation, for example, chemical design and interfacial engineering of p-type doped HTMs for stable and efficient hybrid perovskite photovoltaics.

New salts of teriflunomide TFM (drug approved for Multiple Sclerosis treatment) with inorganic counterions: lithium (TFM_Li), sodium (TFM_Na), potassium (TFM_K), rubidium (TFM_Rb), caesium (TFM_Cs) and ammonium (TFM_NH4) were prepared and investigated employing solid state NMR Spectroscopy, Powder X-ray Diffraction PXRD and Single Crystal X-ray Diffraction (SC XRD). Crystal and molecular structures of three salts: TFM_Na (CCDC: 2173257), TFM_Cs (CCDC: 2165288) and TFM_NH4 (CCDC: 2165281) were determined and deposited. Compared to the native TFM, for all crystalline salt structures, a conformational change of the teriflunomide molecule involving about 180-degree rotation of the end group, forming an intramolecular hydrogen bond N-H⋯O is observed. By applying a complementary multi-technique approach, employing 1D and 2D solid state MAS NMR techniques, single and powder X-ray diffraction measurements, as well as the DFT-based GIPAW calculations of NMR chemical shifts for TFM_Na and TFM_Cs allowed to propose structural features of TFM_Li for which it was not possible to obtain adequate material for single crystal X-Ray measurement.

Safinamide mesylate (SM), the pure active pharmaceutical ingredient (API) recently used in Parkinson disease treatment, recrystallized employing water-ethanol mixture of solvents (vol/vol 1:9) gives a different crystallographic form compared to SM in Xadago tablets. Pure SM crystallizes as a hemihydrate in the monoclinic system with the P21 space group. Its crystal and molecular structure were determined by means of cryo X-ray crystallography at 100 K. SM in the Xadago tablet exists in anhydrous form in the orthorhombic crystallographic system with the P212121 space group. The water migration and thermal processes in the crystal lattice were monitored by solid-state NMR spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. SM in Xadago in the high-humidity environment undergoes phase transformation to the P21 form which can be easily reversed just by heating up to 80 °C. For the commercial form of the API, there is also a reversible thermal transformation observed between Z' = 1 ↔ Z' = 3 crystallographic forms in the 0-20 °C temperature range. Analysis of molecular motion in the crystal lattice proves that the observed conformational polymorphism is forced by intramolecular dynamics. All above-mentioned processes were analyzed and described employing the NMR crystallography approach with the support of advanced theoretical calculations.