Xylazine HCl (X) is a veterinary analgesic with many known solid forms, making it an ideal system for studying the noncovalent interactions, such as hydrogen bonding, that provide stability to polymorphs, solvates/hydrates, and cocrystal of pharmaceuticals. Herein, we report methods for the reliable preparation and interconversion of polymorphs of X (including mechanochemical pathways), the discovery of a novel polymorph, and the synthesis of three cocrystals with coformers containing amide and carboxylic acid moieties. An understanding of ball milling protocols is essential for optimizing these reactions and ensuring clean and reproducible syntheses of the products in high yields. All materials were characterized using thermal analysis, powder and single-crystal X-ray diffraction (PXRD and SCXRD), and multinuclear solid-state NMR (SSNMR) spectroscopy. 35Cl SSNMR is highlighted for its versatility for fingerprinting polymorphs, hydrates, and cocrystals (including the detection of impurity phases that are not always evident from PXRD and offering an avenue for optimizing synthetic protocols) and providing molecular-level structural information. The 35Cl electric field gradient (EFG) tensor is extremely sensitive to the unique hydrogen-bonding network in each solid form of X, resulting in distinct powder patterns. Dispersion-corrected plane-wave density functional theory (DFT) structural refinements yield better models of the hydrogen-bonding environments of the chloride ions than is possible through XRD methods alone. Calculations employing the refined structures yield 35Cl EFG tensors that agree well with experiment. PXRD and 35Cl SSNMR, in tandem with reliable calculations of EFG tensors, are essential for the development of NMR crystallographic and crystal structure prediction protocols and crucial for future studies involving HCl salts and their concomitant solid forms.

Mechanochemical synthesis provides new pathways for the rational design of multi-component crystals (MCCs) involving anionic or cationic components, which offer molecular-level architectures unavailable to MCCs comprised of strictly neutral components....

Functionalized benzenedithiolate complexes of Pt and Pd were prepared by oxidative addition of a library of 1,2,5,6-tetrathiocins to M₂(dba)₃. The oxidation potentials of crown-ether derivatives were increased upon binding Na⁺ ions.

Cocrystallization of the dithiadiazolyl (DTDA) radicals p-XC 6 F 4 CNSSN (X=F, Cl, Br, I, CN) with TEMPO afforded the 2 : 1 cocrystals [p-XC 6 F 4 CNSSN] 2 [TEMPO] (1-5) whose structures all reflect a common S 4 •••O supramolecular motif.The nature of this interaction was probed by DFT calculations (M06/aug-cc-pVDZ) on 1 which revealed that the enthalpy of formation of the [C 6 F 5 CNSSN] 2 [TEMPO] supramolecular motif from [C 6 F 5 CNSSN] 2 and TEMPO is substantial (À 54.0 kJ mol À 1 ). Electronic structure calculations revealed a TEMPO-based doublet S = 1 = 2 configuration as the ground state with limited spin density on the DTDA rings (2.4 %). The corresponding spin quartet state is + 78.9 kJ mol À 1 higher in energy. An atoms-in-molecules analysis reveals four bond critical points (BCPs) between the TEMPO O and the DTDA S atoms as well as additional BCPs between selected DTDA S atoms and methyl H atoms of the TEMPO molecule. Herein, the structures of 2-5 are considered within the context of a hierarchical view of competing and complementary intermolecular interactions; in particular, the established supramolecular CN•••SÀ S synthon is sacrificed in order to form the new S 4 •••O interaction.

The synthesis and reactivity patterns of the strained dithiete ring are compared with their dimeric tetrathiocin counterparts and higher oligomers, highlighting: (i) their cycloaddition chemistry with organic dienophiles as a...

Oxidative addition of the 4′,4″,5′,5″-crown-functionalized dibenzo-1,2,5,6-tetrathiocins, [(OCH 2 CH 2 ) n OC 6 H 2 S 2 ] 2 (1, n = 4; 2, n = 5), to the Co(I) complex CpCo(CO) 2 under microwave irradiation in toluene affords 16e − Co(III) dithiolate complexes CpCo{S 2 C 6 H 2 O(CH 2 CH 2 O) n } 3 (n = 4) and 4 (n = 5) in 71−75% recovered yield. Complexes 3 and 4 were characterized by X-ray diffraction. Compound 3 was found to be polymorphic, crystallizing as the 16e − monomer, 3, or the 18e − dimer, (3) 2 , depending upon reaction conditions. In contrast to previous literature which suggested formation of 1:1 complexes between 3 and s-block cations, reaction of 3 with the s-block metal salts M[BPh 4 ] (M = Na, K, Rb, and Cs) formed the 2:1 complexes [{CpCo(S 2 C 6 H 2 O-(CH 2 CH 2 O) 4 )} 2 M][BPh 4 ] (5a−5d, respectively) whose structures were determined by X-ray diffraction and revealed that the alkali metal ion is sandwiched by two crown ether substituents in all cases. UV/vis titration studies of complex 3 with NaBPh 4 were consistent with formation of the 2:1 complex as the dominant species in solution. Mass spectrometry studies on 5a−5d revealed the presence of both [(3) 2 M] + and [(3)M] + ions (M = Na, K, Rb, and Cs). Electrochemical studies on 3 revealed an irreversible 1e − oxidation attributed to a ligand-based process based on DFT calculations. Chemical oxidation of 3 afforded two dimeric structures [{CpCo(S 2 C 6 H 2 O(CH 2 CH 2 O) 4 )} 2 ][X] 2 (6a, X = OTf; 6b, X = BF 4 ) in which dithiolate ligand oxidation leads to complexes containing a disulfide bond, consistent with electrochemical and computational studies.

Magnetic resonance imaging (MRI) is a widely used non-invasive medical imaging tool. Nanoparticle-based MRI contrast agents have received considerable attention due to their high loading capability for magnetic species, enhanced accumulation in lesions, and versatile surface functionalization. Anisotropic nanoparticles such as nanofibers can exhibit significant advantages over their well-explored spherical counterparts in terms of their pharmacokinetic and biodistribution profiles. Herein, we report the retrosynthetic design, synthesis, and characterization of uniform and length-tunable paramagnetic core-shell nanofibers for MRI through the use of the seeded-growth “living” crystallization-driven self-assembly (CDSA) approach. Triblock copolymer (TriBCP) precursors with a crystallizable polycarbonate core-forming segment, a nitroxide-bearing central region, and a hydrophilic poly(ethylene glycol) (PEG) terminal corona-forming segment were prepared via sequential living organocatalytic ring-opening polymerization (ROP). Low dispersity nanofibers of length ca. 80 nm relevant for biomedical applications were prepared for detailed studies by living CDSA and these possessed an average number of nitroxides per nanofiber of >8000. Subsequent evaluation of the water-proton relaxivities demonstrated that tuning the hydrophilicity of the central segment in the TriBCP allowed access to nanofibers with impressive performance compared to most existing polymer-based nitroxide-based contrast agents. As a result of their 1D morphology, the synthetic nanofibers therefore represent promising organic radical contrast agents (ORCAs) for MRI applications.

Herein, we report the synthesis of an acyclic carbene-stabilized diphospha(aminyl) PNP radical CAAC Me PNPCAAC Me 4 (CAAC Me = 1-[2,6-bis(isopropyl)phenyl]-3,3,5,5-tetramethyl-2-pyrrolidinylidene) by a facile onepot, seven-electron reduction of hexachlorophosphazene chloride [Cl 3 PNPCl 3 ][Cl]. The PNP radical 4 features a conjugated framework with spin density primarily localized on the central nitrogen atom as well as the flanking carbenes. Unlike other tripnictogen radicals, 4 undergoes facile one-electron oxidation and reduction to yield nonclassical nitrenium and amide species [5] + and [6] − , respectively. The cation [5] + exhibits conformational flexibility in the solution state between the expected W-shaped geometry [5 b ] + and a previously unobserved linear heteroallene-type structure [5 a ] + , which was characterized in the solid state. The equilibrium was explored both computationally and experimentally, showing that [5 a ] + is favored over [5 b ] + both enthalpically (ΔH = −2.9 × 10 3 ± 80 J mol −1 ) and entropically (ΔS = 4.2 ± 0.25 J mol −1 K −1 ). The formal amide [6] − displays remarkable flexibility in its coordination chemistry due to the presence of multiple Lewis basic centers, as evidenced by the structure of its potassium complex K 2 6 2 , which exhibits μ, κ-P, κ-P, and η 3 -PNP coordination modes. Protonation of [6] − leads to the formation of an amine 7, which features a trigonal planar geometry around nitrogen.