High-Z′ Crystal Structure of Tricyclic Imidazonaphthyridine Derivatives and the Thermal Profiles of Their Polymorphs

Abstract

The crystal structures and thermal profiles of three crystal polymorphs of tricyclic imidazonaphthyridine derivatives (INA) were investigated. The aniline derivative INA−AN, in which a 4-anilino moiety was introduced at position 9 of the imidazonaphthyridine framework, yielded a nonplanar curved structure between imidazonaphthyridine and aniline. Three crystals (INA−AN-α (I4 1 /a with Z′ = 1) as an emissive polymorph, as well as INA−AN-β1 and INA−AN-β2 (Pc with Z′ = 4) as nonemissive polymorphs) were obtained. The polymorphs comprised multiple-hydrogen-bond networks. INA−AN-β1 and -β2 crystallized into different polymorphs via recrystallization: INA−AN-β1 and -β2 were obtained from the solvent, as well as via melting and recrystallization processes. Notably, the crystal structures and parameters of INA−AN-β1 and -β2 largely corresponded, although their thermal behaviors were significantly different: INA−AN-β1 underwent a thermal crystal transformation, yielding INA−AN-α at ∼185 °C, while INA−AN-β2 readily melted at ∼190 °C. These distinct profiles indicated that the subtle distinct molecular arrangements, as well as crystal packings, might account for the different thermal profiles of INA−INA-β polymorphs. Interestingly, in addition to INA−AN-β polymorphs, an imidazonaphthyridine framework bearing an N,N-dimethylamine moiety, INA−DMA, crystallized in the P1̅ space group with Z′ = 4, indicating that the INA framework containing an aromatic ring afforded high-Z′ crystal structures.

Basic Fluorescent Protonation-Type pH Probe Sensitive to Small ΔpKa of Methanol and Ethanol

“… , It is expected that the introduction of a guanidine moiety as an electron-donating group increases the basicity of the fluorophores because guanidines are known as strong organobases (organosuperbases) due to the resonance stabilization of their conjugated acids. − Subsequently, to determine the p K BH+ values of the synthesized compounds, the pH-dependent absorption spectra of guanidine fluorophores were recorded in a Britton–Robinson buffer solution with a molecular concentration of 25 μM (Figures S1–S3). As shown in Figure , the p K BH+ values of guanidine fluorophores 1–3 increased to 9.0, 9.6, and 9.9, respectively. These p K BH+ values were much higher than those of the parent molecules TFMAQ, BQL, and BQA (0.9, 1.8, and 2.2, respectively).…”

“…pH-dependent absorption spectral changes of 1–5 are shown in Figures S1–S5. The p K BH+ values were determined via UV–vis spectroscopy, as described in our previous work . The 25 μM solutions 1–5 containing 30% (v/v) 1,4-dioxane/buffer were used as the working solutions.…”

Acid responsiveness of emissive morpholinyl aminoquinolines and their use for cell fluorescence imaging

“…The p K a values were determined via UV-Vis spectroscopy, as described in our previous work. 34 Solutions containing 20 μM of compounds 1–5 in 1% or 10% (v/v) DMSO/buffer were used as the working solutions. Buffer solutions with different pH values were prepared using the Britton–Robinson buffer (pH = 2–12 and HCl solution (pH = 1).…”

Order–Disorder Phase Transition between High- and Low-Z′ Crystal Structures of the P1 Space Group

“…Polymorphic phase transition, defined as a transition of a crystalline phase at a certain temperature and pressure to another crystalline phase of the same composition with different crystal structures, is a critical phenomenon in the field of pharmaceutical chemistry because the different physical properties of polymorphs such as bioavailability and solubility also have intellectual property rights. , Crystal structures with a large number of molecules in the asymmetric unit ( Z ′), i.e., high- Z ′, are not only a scientific curiosity but also attract many scientists as an informative subset of crystal structures to understand crystallization and polymorphism. − Indeed, the new crystal structure of a simple compound, the hydrochloride salt of fampridine, where Z ′ = 30, was recently reported as a Frank–Kasper (FK) phase, and this class of materials is expected to open new perspectives in the field of supramolecular chemistry and material science . Peptide compounds, which have recently attracted attention as building blocks of porous materials , and are being developed for use as a promising class of molecular pharmaceutics, − have been reported to exhibit many polymorphs due to the conformational flexibility derived from the side chain structure of amino acids.…”