Mixed Metal Amide-Hydride Solid Solutions for Potential Energy Storage Applications.

Mixed solid solutions have played an important role in improving the kinetics and performance of hydrogen storage materials, as reported for the Li-Mg-N-H, K-Mg-N-H, and Rb-Mg-N-H systems. Besides, the formation of a homogeneous solid solution, mostly due to partial ionic substitution, is known to be an effective approach to improve the ionic conductivity of a material, which is an important property in electrochemical applications. We have reported a series of solid solutions based on mixed amide-hydride materials of the Group 1 elements, e.g., K(NH2)xH1-x, Rb(NH2)xH1-x, and Cs(NH2)xH1-x, via the exchange of NH2-/H- anions with the change of the lattice cell of the solid solution. Extending the research in this direction, we study the M-N-H solid solution in the MNH2-MH systems (M = K, Rb, Cs, and their combinations), i.e., KNH2-RbH, RbNH2-KH, RbNH2-CsH, and CsNH2-RbH via ex situ/in situ XRD, IR, and 1H 2D solid-state NMR. The results obtained confirm the formation of mixed metal amide-hydride solid solutions associated with an exchange between both anionic (NH2- and H-) and cationic species (K+, Rb+, and Cs+). With this study, we aim to create an accessible library of M-N-H solid solutions for further studies as additives for hydrogen storage materials or ionic conductors.

One-Dimensional and Two-Dimensional Zn(II) Coordination Polymers with Ditopic Imidazo[1,5-a]pyridine: A Structural and Computational Study.

Zn(II) coordination polymers are being increasingly studied for their stability and properties. Similarly, there is a growing interest in imidazo[1,5-a]pyridine derivatives, which show great potential in luminescence and pharmaceutical applications. In this work, we successfully synthesized and crystallized three new coordination polymers, using Zn(II) as the metallic node, dicarboxylic acids of different length and nature as linkers, and a linear ditopic imidazo[1,5-a]pyridine derivative, to explore the role of this molecule as a propagator of the dimensionality of the structure or as an ancillary ligand. Our work demonstrates the structural capability of imidazo[1,5-a]pyridines in an unexplored domain for this family of ligands. Notably, we observed a pronounced ability of this heterocyclic scaffold to establish π···π interactions in the solid state. The supramolecular π-stacked assemblies were theoretically analyzed using DFT calculations based on model structures.

Mechanochemical Preparation, Solid-State Characterization, and Antimicrobial Performance of Copper and Silver Nitrate Coordination Polymers with L- and DL-Arginine and Histidine.

The antimicrobial activity of the novel coordination polymers obtained by co-crystallizing the amino acids arginine or histidine, as both enantiopure L and racemic DL forms, with the salts Cu(NO3)2 and AgNO3 has been investigated to explore the effect of chirality in the cases of enantiopure and racemic forms. The compounds [Cu·AA·(NO3)2]CPs and [Ag·AA·NO3]CPs (AA = L-Arg, DL-Arg, L-His, DL-His) were prepared by mechanochemical, slurry, and solution methods and characterized by X-ray single-crystal and powder diffraction in the cases of the copper coordination polymers, and by powder diffraction and by solid-state NMR spectroscopy in the cases of the silver compounds. The two pairs of coordination polymers, [Cu·L-Arg·(NO3)2·H2O]CP and [Cu·DL-Arg·(NO3)2·H2O]CP, and [Cu·L-Hys·(NO3)2·H2O]CP and [Cu·DL-His·(NO3)2·H2O]CP, have been shown to be isostructural in spite of the different chirality of the amino acid ligands. A similar structural analogy could be established for the silver complexes on the basis of SSNMR. The activity against the bacterial pathogens Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus was assessed by carrying out disk diffusion assays on lysogeny agar media showing that, while there is no significant effect arising from the use of enantiopure or chiral amino acids, the coordination polymers exert an appreciable antimicrobial activity comparable, when not superior, to that of the metal salts alone.

Zwitterionic or Not? Fast and Reliable Structure Determination by Combining Crystal Structure Prediction and Solid-State NMR.

When it comes to crystal structure determination, computational approaches such as Crystal Structure Prediction (CSP) have gained more and more attention since they offer some insight on how atoms and molecules are packed in the solid state, starting from only very basic information without diffraction data. Furthermore, it is well known that the coupling of CSP with solid-state NMR (SSNMR) greatly enhances the performance and the accuracy of the predictive method, leading to the so-called CSP-NMR crystallography (CSP-NMRX). In this paper, we present the successful application of CSP-NMRX to determine the crystal structure of three structural isomers of pyridine dicarboxylic acid, namely quinolinic, dipicolinic and dinicotinic acids, which can be in a zwitterionic form, or not, in the solid state. In a first step, mono- and bidimensional SSNMR spectra, i.e., 1H Magic-Angle Spinning (MAS), 13C and 15N Cross Polarisation Magic-Angle Spinning (CPMAS), 1H Double Quantum (DQ) MAS, 1H-13C HETeronuclear CORrelation (HETCOR), were used to determine the correct molecular structure (i.e., zwitterionic or not) and the local molecular arrangement; at the end, the RMSEs between experimental and computed 1H and 13C chemical shifts allowed the selection of the correct predicted structure for each system. Interestingly, while quinolinic and dipicolinic acids are zwitterionic and non-zwitterionic, respectively, in the solid state, dinicotinic acid exhibits in its crystal structure a "zwitterionic-non-zwitterionic continuum state" in which the proton is shared between the carboxylic moiety and the pyridinic nitrogen. Very refined SSNMR experiments were carried out, i.e., 14N-1H Phase-Modulated (PM) pulse and Rotational-Echo Saturation-Pulse Double-Resonance (RESPDOR), to provide an accurate N-H distance value confirming the hybrid nature of the molecule. The CSP-NMRX method showed a remarkable match between the selected structures and the experimental ones. The correct molecular input provided by SSNMR reduced the number of CSP calculations to be performed, leading to different predicted structures, while RMSEs provided an independent parameter with respect to the computed energy for the selection of the best candidate.

Solid-State NMR-Driven Crystal Structure Prediction of Molecular Crystals: The Case of Mebendazole.

Among all possible NMR crystallography approaches for crystal-structure determination, crystal structure prediction - NMR crystallography (CSP-NMRX) has recently turned out to be a powerful method. In the latter, the original procedure exploited solid-state NMR (SSNMR) information during the final steps of the prediction. In particular, it used the comparison of computed and experimental chemical shifts for the selection of the correct crystal packing. Still, the prediction procedure, generally carried out with DFT methods, may require important computational resources and be quite time-consuming, especially if there are no available constraints to use at the initial stage. Herein, the successful application of this combined prediction method, which exploits NMR information also in the input step to reduce the search space of the predictive algorithm, is presented. Herein, this method was applied on mebendazole, which is characterized by desmotropism. The use of SSNMR data as constraints for the selection of the right tautomer and the determination of the number of independent molecules in the unit cell led to a considerably faster process, reducing the number of calculations to be performed. In this way, the crystal packing was successfully predicted for the three known phases of mebendazole. To evaluate the quality of the predicted structures, these were compared to the experimental ones. The crystal structure of phase B of mebendazole, in particular, was determined de novo by powder diffraction and is presented for the first time in this paper.

Solid-State Dynamics and High-Pressure Studies of a Supramolecular Spiral Gear.

The structures and solid-state dynamics of the supramolecular salts of the general formula [(12-crown-4)2 ⋅DABCOH2 ](X)2 (where DABCO=1,4-diazabicyclo[2.2.2]octane, X=BF4 , ClO4 ) have been investigated as a function of temperature (from 100 to 360 K) and pressure (up to 3.4 GPa), through the combination of variable-temperature and variable-pressure XRD techniques and variable-temperature solid-state NMR spectroscopy. The two salts are isomorphous and crystallize in the enantiomeric space groups P32 21 and P31 21 . All building blocks composing the supramolecular complex display dynamic processes at ambient temperature and pressure. It has been demonstrated that the motion of the crown ethers is maintained on lowering the temperature (down to 100 K) or on increasing the pressure (up to 1.5 GPa) thanks to the correlation between neighboring molecules, which mesh and rotate in a concerted manner similar to spiral gears. Above 1.55 GPa, a collapse-type transition to a lower-symmetry ordered structure, not attainable at a temperature of 100 K, takes place, proving, thus, that the pressure acts as the means to couple and decouple the gears. The relationship between temperature and pressure effects on molecular motion in the solid state has also been discussed.

Fluorinated PLGA Nanoparticles for Enhanced Drug Encapsulation and 19 F†NMR Detection.

In the continuous search for multimodal systems with combined diagnostic and therapeutic functions, several efforts have been made to develop multifunctional drug delivery systems. In this work, through a covalent approach, a new class of fluorinated poly(lactic-co-glycolic acid) co-polymers (F-PLGA) were designed that contain an increasing number of magnetically equivalent fluorine atoms. In particular, two novel compounds, F3 -PLGA and F9 -PLGA, were synthesized and their chemical structure and thermal stability were analyzed by solution NMR, DSC, and TGA. The obtained F-PLGA compounds were proven to form in aqueous solution colloidal stable nanoparticles (NPs) displaying a strong 19 F NMR signal. The fluorinated NPs also showed an enhanced ability to load hydrophobic drugs containing fluorine atoms compared to analogous pristine PLGA NPs. Preliminary in vitro studies showed high cell viability and the NP ability to intracellularly deliver and release a functioning drug.

Investigation of Dimethylammonium Solubility in MAPbBr3 Hybrid Perovskite: Synthesis, Crystal Structure, and Optical Properties.

The possible existence of mixed methylammonium (MA)/dimethylammonium (DMA) lead bromide hybrid perovskites of general formula MA1- xDMA xPbBr3 (0 ≤ x ≤ 1) was investigated. A combined X-ray diffraction and solid-state nuclear magnetic resonance approach indicates that DMA can be incorporated up to about x = 0.30 while retaining the cubic lattice of MAPbBr3. By increasing the DMA content ( x), the absorption shows a progressive blue shift and the band gap moves from about 2.17 eV ( x = 0) to about 2.23 ( x = 0.30) with a concomitant slightly faster recombination in the mixed cation powders.

Determination of the 15 N chemical shift anisotropy in natural abundance samples by proton-detected 3D solid-state NMR under ultrafast MAS of 70 kHz.

Chemical shift anisotropy (CSA) is a sensitive probe of electronic environment at a nucleus, and thus, it offers deeper insights into detailed structural and dynamic properties of different systems, for example, chemical, biological, and materials. Over the years, massive efforts have been made to develop recoupling methods that reintroduce CSA interaction under magic angle spinning (MAS) conditions. Most of them require slow or moderate MAS (≤20 kHz) and isotopically enriched samples. On the other hand, to the best of the authors' knowledge, no 13 C or 15 N CSA recoupling schemes at ultrafast MAS (≥60 kHz) suitable for cost-effective natural abundant samples have been developed. We present here a proton-detected 3D 15 N CS/15 N CSA/1 H CS correlation experiment which employs 1 H indirect detection for sensitivity enhancement and a γ-encoded RNnν -symmetry-based CSA recoupling scheme. In particular, two different symmetries, that is, R837 and R1049 , are first tested, in a 2D 15 N CSA/1 H CS version, on [U-15 N]-L-histidine·HCl·H2 O as a model sample under 70 kHz MAS. Then the 3D experiment is applied on glycyl-L-alanine at natural abundance, resulting in site-resolved 15 N CSA lineshapes from which CSA parameters are retrieved by SIMPSON numerical fittings. We demonstrate that this 3D R-symmetry-based pulse sequence is highly robust with respect to wide-range offset mismatches and weakly dependent to rf inhomogeneity within mis-sets of ±10% from the theoretical value.

Precessional Motion in Crystalline Solid Solutions of Ionic Rotors.

The order-disorder phase transition associated with the uprise of reorientational motion in (DABCOH2)2+ , in the supramolecular salts of general formula [1⋅(DABCOH2 )]X2 (where 1=12-crown-4, DABCO=1,4-diazabicyclo[2.2.2]octane, and X=Cl- or Br- ), has been investigated by variable temperature X-ray diffraction on single crystals and powder samples, as well as by DSC and solid-state NMR spectroscopy (SSNMR). The two compounds undergo a reversible phase change at 292 and 290 K, respectively. The two crystalline materials form solid solutions [1⋅(DABCOH2 )]Cl2x Br2(1-x) in the whole composition range (0 < x<1), with a decrease in the temperature of transition to a minimum of ca 280 K, corresponding to x=0.5. Activation energy values for the dynamic processes, evaluated by variable-temperature 13 C magic-angle spinning (MAS) SSNMR and line-shape analysis are ca. 50 kJ mol-1 in all cases. Combined diffraction and spectroscopic evidence has allowed the detection of a novel dynamic process for the (DABCOH2 )2+ dications, based on a room temperature precessional motion that is frozen out below the disorder-order transition; to the best of the authors' knowledge this phenomenon has never been observed before.

Insights into the Rb-Mg-N-H System: an Ordered Mixed Amide/Imide Phase and a Disordered Amide/Hydride Solid Solution.

The crystal structure of a mixed amide-imide phase, RbMgND2ND, has been solved in the orthorhombic space group Pnma ( a = 9.55256(31), b = 3.70772(11) and c = 10.08308(32) Å). A new metal amide-hydride solid solution, Rb(NH2) xH(1- x), has been isolated and characterized in the entire compositional range. The profound analogies, as well as the subtle differences, with the crystal chemistry of KMgND2ND and K(NH2) xH1- x are thoroughly discussed. This approach suggests that the comparable performances obtained using K- and Rb-based additives for the Mg(NH2)2- 2LiH and 2LiN H2-MgH2 hydrogen storage systems are likely to depend on the structural similarities of possible reaction products and intermediates.

Halogen-Bond Effects on the Thermo- and Photochromic Behaviour of Anil-Based Molecular Co-crystals.

N-Salicilideneanilines are among the most studied thermo- and photochromic systems in the solid state. Although thermochromism is a general property of crystalline N-salicilideneanilines, photochromism is known in a limited number of cases. As a method for the construction of thermo- and photo-responsive molecular architectures, the co-crystallisation of 1,2,4,5-tetrafluoro-3,6-diiodobenzene (I2F4) with three selected imines of o-vanillin, named 1, 2 and 3, obtained through a condensation reaction with 3-aminopyridine, 4-bromoaniline and 4-iodoaniline, respectively, is reported herein. All crystals and co-crystals have been characterised by means of solid-state complementary techniques (X-ray diffraction, solid-state NMR spectroscopy, absorption and emission spectroscopy). The role of halogen bonding and crystal packing in the optical and chromic properties of all solid materials is discussed. All solids exhibit thermochromic behaviour, and three of them (2, 22 ⋅I2F4 and 32 ⋅I2F4) are also photochromic. Imine derivative 3 crystallises in two different polymorphic forms (3 A and 3 B) and a solvate (3Solv ). The bromo and iodo derivatives, 2 and 3 B, are isomorphous and form isomorphous co-crystals with I2F4, but behave differently when exposed to UV light because only crystalline 2 is photochromic. Interestingly, the replacement of bromine with iodine seems to turn off the photochromism because crystalline 3 A and 3Solv , and even the 20.7 30.3 solid solution, do not manifest photochromic behaviour.

Proton in a Confined Space: Structural Studies of H+ ⊂Crypt-111 Iodide and Some Halogen-Bonded Derivatives.

Experimental observations and modeling data are reported on the solid-state structural features of crypt- 111⋅HI (1) and the three-component co-crystals that 1 forms with α,ω-diiodoperfluoroalkanes 2 a-d. X-ray analyses indicate that, in all five systems and at low temperature, the caged proton is covalently bonded to a single nitrogen atom and is involved in a network of intramolecular hydrogen bonds. In contrast, room-temperature, solid-state 15 N NMR spectroscopy suggests magnetic equivalency of the two N atoms of crypt-111 in both 1 and co-crystals of 1 with diiodoperfluoroalkanes. Computational modelling confirms that the acidic hydrogen inside the cavity preferentially sits along the internitrogen axis and is covalently bonded to one nitrogen. The computed energy barriers suggest that the hopping of the encapsulated proton between the two N atoms of the cage can occur in the halogen-bonded co-crystals of 1⋅2, but it is hardly possible in the pure H+ ⊂crypt-111 iodide 1. These different pictures of the proton position and dynamics obtained by using different techniques and conditions confirm the unique characteristics of the confined space within the cavity of crypr-111 and the distinctive features of processes occurring therein.

Natural Abundance 15 N and 13 C Solid-State NMR Chemical Shifts: High Sensitivity Probes of the Halogen Bond Geometry.

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a versatile characterization technique that can provide a plethora of information complementary to single crystal X-ray diffraction (SCXRD) analysis. Herein, we present an experimental and computational investigation of the relationship between the geometry of a halogen bond (XB) and the SSNMR chemical shifts of the non-quadrupolar nuclei either directly involved in the interaction (15 N) or covalently bonded to the halogen atom (13 C). We have prepared two series of X-bonded co-crystals based upon two different dipyridyl modules, and several halobenzenes and diiodoalkanes, as XB-donors. SCXRD structures of three novel co-crystals between 1,2-bis(4-pyridyl)ethane, and 1,4-diiodobenzene, 1,6-diiodododecafluorohexane, and 1,8-diiodohexadecafluorooctane were obtained. For the first time, the change in the 15 N SSNMR chemical shifts upon XB formation is shown to experimentally correlate with the normalized distance parameter of the XB. The same overall trend is confirmed by density functional theory (DFT) calculations of the chemical shifts. 13 C NQS experiments show a positive, linear correlation between the chemical shifts and the C-I elongation, which is an indirect probe of the strength of the XB. These correlations can be of general utility to estimate the strength of the XB occurring in diverse adducts by using affordable SSNMR analysis.

Novel composite plastics containing silver(I) acylpyrazolonato additives display potent antimicrobial activity by contact.

New silver(I) acylpyrazolonato derivatives displaying a mononuclear, polynuclear, or ionic nature, as a function of the ancillary azole ligands used in the synthesis, have been fully characterized by thermal analysis, solution NMR spectroscopy, solid-state IR and NMR spectroscopies, and X-ray diffraction techniques. These derivatives have been embedded in polyethylene (PE) matrix, and the antimicrobial activity of the composite materials has been tested against three bacterial strains (E. coli, P. aeruginosa, and S. aureus): Most of the composites show antimicrobial action comparable to PE embedded with AgNO3 . Tests by contact and release tests for specific migration of silver from PE composites clearly indicate that, at least in the case of the PE, for composites containing polynuclear silver(I) additives, the antimicrobial action is exerted by contact, without release of silver ions. Moreover, PE composites can be re-used several times, displaying the same antimicrobial activity. Membrane permeabilization studies and induced reactive oxygen species (ROS) generation tests confirm the disorganization of bacterial cell membranes. The cytotoxic effect, evaluated in CD34(+) cells by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazoliumbromide) and CFU (colony forming units) assays, indicates that the PE composites do not induce cytotoxicity in human cells. Studies of ecotoxicity, based on the test of Daphnia magna, confirm tolerability of the PE composites by higher organisms and exclude the release of Ag(+) ions in sufficient amounts to affect water environment.

Polyoxometalate complexes of anatase-titanium dioxide cores in water.

Polyoxometalate (POM) cluster anions are shown to serve as covalently coordinated ligands for anatase-TiO2 nanocrystals, giving isolable assemblies uniquely positioned between molecular macroanions and traditional colloidal nanoparticles. Na(+) salts of the water-soluble polyanionic structures are obtained by reacting amorphous TiO2 with the 1 nm lacunary ion, Na7 [α-XW11 O39 ] (X=P(5+) ), at 170 °C, after which an average of 55 α-PW11 O39 (7-) clusters are found as pentadentate ligands for Ti(IV) ions covalently linked to 6 nm single-crystal anatase cores. The attached POMs are reversible electron acceptors, the reduction potentials of which shift in a predictable fashion by changing the central heteroatom, X, directly influencing a model catalytic reaction. Just as POM cluster anions control the reactivities of metal centers in molecular complexes, directly coordinated POM ligands with tunable redox potentials now provide new options for rationally controlling the reactions of semiconductor nanocrystals.

Probing hydrogen bond networks in half-sandwich Ru(II) building blocks by a combined 1H DQ CRAMPS solid-state NMR, XRPD, and DFT approach.

The hydrogen bond network of three polymorphs (1α, 1ß, and 1γ) and one solvate form (1·H2O) arising from the hydration-dehydration process of the Ru(II) complex [(p-cymene)Ru(κN-INA)Cl2] (where INA is isonicotinic acid), has been ascertained by means of one-dimensional (1D) and two-dimensional (2D) double quantum (1)H CRAMPS (Combined Rotation and Multiple Pulses Sequences) and (13)C CPMAS solid-state NMR experiments. The resolution improvement provided by homonuclear decoupling pulse sequences, with respect to fast MAS experiments, has been highlighted. The solid-state structure of 1γ has been fully characterized by combining X-ray powder diffraction (XRPD), solid-state NMR, and periodic plane-wave first-principles calculations. None of the forms show the expected supramolecular cyclic dimerization of the carboxylic functions of INA, because of the presence of Cl atoms as strong hydrogen bond (HB) acceptors. The hydration-dehydration process of the complex has been discussed in terms of structure and HB rearrangements.

Enantiospecific crystallisation behaviour of malic acid in mechanochemical reactions with vinpocetine.

We report an intriguing example of enantioselectivity in the formation of new multicomponent crystalline solid containing vinpocetine and malic acid. Several experimental data sets confirmed that the multicomponent system presents a clear enantiospecific crystallisation behaviour both in the solid-state and in solution: only the system consisting of vinpocetine and L-malic acid produces a free-flowing solid consisting of a new crystalline form, while the experiments with D-malic acid produced an amorphous and often deliquescent material. The new vinpocetine-L-malic system crystallizes in the monoclinic space group of P21 and in a 1:1 molar ratio, where the two molecules are linked through intermolecular hydrogen bonds in the asymmetric unit. The vinpocetine-DL-malic system was partially crystalline (with also traces of unreacted vinpocetine) with diffraction peaks corresponding to those of vinpocetine-L-malic acid. Solid-state NMR experiments revealed strong ionic interactions in all the three systems. However, while vinpocetine-L-malic acid system was a pure and crystalline phase, the other two systems persistently showed the presence of unreacted vinpocetine. This resulted in a significant worsening of the dissolution profile with respect to the pure vinpocetine-L-malic crystalline salt, whose dissolution kinetics appeared superior.

Shifting the Focus from Dissolution to Permeation: Introducing the Meso-fluidic Chip for Permeability Assessment (MCPA).

In response to the growing ethical and environmental concerns associated with animal testing, numerous in vitro tools of varying complexity and biorelevance have been developed and adopted in pharmaceutical research and development. In this work, we present one of these tools, i.e., the Meso-fluidic Chip for Permeability Assessment (MCPA), for the first time. The MCPA combines an artificial barrier (PermeaPad®) with an organ-on-chip device (MIVO®) and real-time automated concentration measurements, to yield a sustainable, yet effortless method for permeation testing. The system offers three major physiological aspects, i.e., a biomimetic membrane, an optimal membrane interfacial area-to-donor-volume-ratio (A/V) and a physiological flow on the acceptor/basolateral side, which makes the MPCA an ideal candidate for mechanistic studies and excellent in vivo bioavailability predictions. We validated the method with a handful of assorted drug compounds in unstirred and stirred donor conditions, before exploring its applicability as a tool for dissolution/permeation testing on a BCS class III/I drug (pyrazinamide) crystalline adducts and BCS class II/IV (hydrocortisone) amorphous solid dispersions. The results were highly reproducible and clearly displayed the method's potential for evaluating the performance of enabling formulations, and possibly even predicting in vivo performance. We believe that, upon further development, the MCPA will serve as a useful in vitro tool that could push sustainability into pharmaceutics by refining, reducing and replacing animal testing in early-stage drug development.

Halogen bonding and pharmaceutical cocrystals: the case of a widely used preservative.

3-Iodo-2-propynyl-N-butylcarbamate (IPBC) is an iodinated antimicrobial product used globally as a preservative, fungicide, and algaecide. IPBC is difficult to obtain in pure form as well as to handle in industrial products because it tends to be sticky and clumpy. Here, we describe the preparation of four pharmaceutical cocrystals involving IPBC. The obtained cocrystals have been characterized by X-ray diffraction, solution and solid-state NMR, IR, and DSC analyses. In all the described cases the halogen bond (XB) is the key interaction responsible for the self-assembly of the pharmaceutical cocrystals thanks to the involvement of the 1-iodoalkyne moiety of IPBC, which functions as a very reliable XB-donor, with both neutral and anionic XB-acceptors. Most of the obtained cocrystals have improved properties with respect to the source API, in terms, e.g., of thermal stability. The cocrystal involving the GRAS excipient CaCl2 has superior powder flow characteristics compared to the pure IPBC, representing a promising solution to the handling issues related to the manufacturing of products containing IPBC.