Intermolecular Interactions in Crystalline Hydroxychloroquine Sulfate in Comparison with Those in Selected Antimalarial Drugs

Abstract The crystal structure of hydroxychloroquine sulfate (OHClQ) was determined in order to compare its conformation and intermolecular interactions to those in the crystalline chloroquine phosphate (ClQP) and quinine salicylate (QSal) monohydrate. The crystals of OHClQ are monoclinic with the space group P2₁/c and unit-cell dimensions: a = 10.4966(1) ?, b = 8.8056(1) ?, c = 21.8603(3) ?, β = 101.074(1)°. The quinoline antimalarial drugs may interact with their putative receptors by formation of characteristic hydrogen-bonded rings. The protonated nitrogen atoms and/or hydroxyl groups of the drug cation are proton donors, while the oxygen atoms of anions are proton acceptors. Water molecules may intermediate in these interactions. Graphical Abstract Hydroxychloroquine sulfate is a drug used in the treatment of malaria and rheumatic diseases. The X-ray structure analysis shows an important role of intermolecular hydrogen bonds in the crystal architecture. Comparison with chloroquine phosphate and quinine salicylate indicates that the organization of the drug cations is determined by the anions.      

1,3-Dipolar cycloadditions with azomethine ylide species generated from aminocyclopropanes

Two types of bicyclic N-cyclopropyl glycine ester derivatives have been prepared and put under scrutiny as possible precursors of azomethine ylides. The results demonstrate that they can indeed participate in 1,3-dipolar cycloaddition reactions with dipolarophiles, as illustrated in the cases of phenyl vinyl sulfone, N-phenylmaleimide, diethyl fumarate and diethyl maleate. The relative configurations of the major diastereoisomers produced are consistent with the predicted generation of azomethine ylide species, reacting in concerted cycloaddition processes. This unprecedented way of generating such 1,3-dipoles provides access to functionalised pyrrolizidine and pyrrolidine derivatives, that would be difficult to make directly by more classic methods. It was also found that using phenyl vinyl sulfone or N-phenylmaleimide as the dipolarophile reactant, a domino nucleophilic conjugate addition/1,3-dipolar cycloaddition process may operate competitively.     

Photochemical stability of poly(vinyl pyrrolidone) in the presence of collagen

The photochemical stability of poly(vinyl pyrrolidone) (PVP) in the presence of 1%, 3% and 5% of collagen has been studied by UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), thermogravimetry analysis (TG) and derivative thermogravimetry (DTG). Surface properties have been studied by contact angle measurements. PVP samples and samples containing 1%, 3% and 5% of collagen were irradiated with UV light of wavelength λ = 254 nm in air for up to 24 h. The amount of gel created during UV irradiation was estimated.PVP in the presence of 1%, 3% and 5% of collagen is less stable both thermally and photochemically. Collagen enhances photochemical processes leading to crosslinking of PVP. The contact angle measurements and values of surface free energy showed that the wettability of PVP films was changed by the addition of collagen and by UV irradiation. The increase of polarity of samples indicates an efficient photooxidation on the surface upon UV irradiation.     

Colorimetric and fluorimetric pH sensing using polydiacetylene embedded within PVC-PCL nanofibers

The applicability of model polydiacetylenes (PDAs) in hydrogen ions sensitive optodes was tested. Nanofibers mats were electrospun using a mixture of polyvinyl chloride (PVC) and polycaprolactone (PCL) together with 10, 12-tricosadiynoic acid (TCDA) or 10,12-pentacosadiynoic acid (PCDA). After the polymerization the mats were applied in colorimetric and fluorimetric pH sensors. The PDAs were formed by photopolymerization with a UV lamp (254 nm), resulting in a change of mats color from white to dark blue. The morphology of both fiber mats is similar (SEM images), and the average diameters of fibers were estimated as equal to 228±73 and 248±61 nm for TCDA and PCDA, respectively. As the pH increases, the color of the fiber mat changes from blue to red and the process can be followed visually. The result obtained by computer image analysis showed a sigmoidal increase in the intensity of red and a decrease in the intensity of blue color with increasing pH. A similar sigmoidal response is observed for the dependence of the emission intensity on the pH. Changes in the recorded signal occur in the pH range from 7 to 8.5 or from 8 to 9.5 for mats with TCDA and PCDA, respectively. Both readout modes can be successfully used for pH sensing with proposed nanofibrous mats in the range of pH close to the physiological pH range.     

α‐Amino Acid‐Isosteric α‐Amino Tetrazoles

The synthesis of all 20 common natural proteinogenic and 4 otherα‐amino acid‐isosteric α‐amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5‐tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α‐amino acid‐isosteric α‐amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non‐natural derivatives is of high interest to advance the field.     

In-situ AFM studies of the phase-transition behavior of single thermoresponsive hydrogel particles

The volume phase transition (VPT) behavior of individual thermally responsive poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) hydrogel microparticles was studied by in-situ dynamic mode atomic force microscopy (AFM) and force spectroscopy during heating and cooling cycles. Hydrogel samples were prepared by electrostatic immobilization of microparticles to amine-modified gold surfaces. The AFM studies of particle deswelling were performed by varying the force applied on the particles during imaging as a function of the geometry and material of the AFM probe. Aluminum-coated silicon cantilevers were found to influence substantially the behavior of the particles during the VPT, leading to a significant shape change. Low force impact magnetic excitation of the AFM probe (MAC mode) during dynamic mode measurements resulted in an undisturbed deswelling behavior enabling observation of the expected volume changes of the particles without significant tip-sample interaction. Hence, MAC-mode AFM was determined to be the most suitable technique for in-situ AFM studies on volume and shape changes at single hydrogel particles during VPT. Elasticity measurements performed at single particles at temperatures below and above the VPT revealed a 15-fold increase in the Young's modulus after passing the VPT, indicating the transition from a soft, swollen network to a stiffer, deswollen state.     

Anharmonicity and Spectra–Structure Correlations in MIR and NIR Spectra of Crystalline Menadione (Vitamin K3)

Mid-infrared (MIR) and near-infrared (NIR) spectra of crystalline menadione (vitamin K₃) were measured and analyzed with aid of quantum chemical calculations. The calculations were carried out using the harmonic approach for the periodic model of crystal lattice and the anharmonic DVPT2 calculations applied for the single molecule model. The theoretical spectra accurately reconstructed the experimental ones permitting for reliable assignment of the MIR and NIR bands. For the first time, a detailed analysis of the NIR spectrum of a molecular system based on a naphthoquinone moiety was performed to elucidate the relationship between the chemical structure of menadione and the origin of the overtones and combination bands. In addition, the importance of these bands during interpretation of the MIR spectrum was demonstrated. The overtones and combination bands contribute to 46.4% of the total intensity of menadione in the range of 3600–2600 cm⁻¹. Evidently, these bands play a key role in shaping of the C-H stretching region of MIR spectrum. We have shown also that the spectral regions without fundamentals may provide valuable structural information. For example, the theoretical calculations reliably reconstructed numerous overtones and combination bands in the 4000–3600 and 2800–1800 cm⁻¹ ranges. These results, provide a comprehensive origin of the fundamentals, overtones and combination bands in the NIR and MIR spectra of menadione, and the relationship of these spectral features with the molecular structure.     

High-Pressure Mechanistic Insight into Bioinorganic NO Chemistry

Pressure is one of the most important parameters controlling the kinetics of chemical reactions. The ability to combine high-pressure techniques with time-resolved spectroscopy has provided a powerful tool in the study of reaction mechanisms. This review is focused on the supporting role of high-pressure kinetic and spectroscopic methods in the exploration of nitric oxide bioinorganic chemistry. Nitric oxide and other reactive nitrogen species (RNS) are important biological mediators involved in both physiological and pathological processes. Understanding molecular mechanisms of their interactions with redox-active metal/non-metal centers in biological targets, such as cofactors, prosthetic groups, and proteins, is crucial for the improved therapy of various diseases. The present review is an attempt to demonstrate how the application of high-pressure kinetic and spectroscopic methods can add additional information, thus enabling the mechanistic interpretation of various NO bioinorganic reactions.     

Isosteric heats of adsorption of carbon dioxide on zeolite MCM-22 modified by alkali metal cations

Adsorption isotherms of carbon dioxide were measured on cation-exchanged (Li⁺, Na⁺, K⁺, Cs⁺) MCM-22 zeolite with the molar ratio of Si/Al=15 and series of Na-MCM-22 of Si/Al molar ratios varying in the range from 15 to 40 at 273, 293, 313 and 333 K. Based on the known temperature dependence of CO₂ adsorption, isosteric heats of adsorption were calculated. The obtained dependences of isosteric heats related to the amount of CO₂ adsorbed have provided detailed insight into the interaction of carbon dioxide molecule with alkali metal cations.