Search

Anna Stasiłowicz,1 Ewa Tykarska,2 Natalia Rosiak,1 Kinga Sałat,3 Anna Furgała-Wojas,3 Tomasz Plech,4 Kornelia Lewandowska,5 Katarzyna Pikosz,1 Kamil Pawłowicz,1 Judyta Cielecka-Piontek1 1Department of Pharmacognosy, Poznan University of Medical Sciences, Poznan, Poland; 2Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznan, Poland; 3Department of Pharmacodynamics, Jagiellonian University Medical College, Krakow, Poland; 4Department of Pharmacology, Medical University of Lublin, Lublin, Poland; 5Institute of Molecular Physics, Polish Academy of Sciences, Poznan, PolandCorrespondence: Judyta Cielecka-PiontekDepartment of Pharmacognosy, Poznan University of Medical Sciences, Swiecickiego 4, 61– 781, Poznan, PolandTel +48 61 854 67 09Fax +48 61 854 67 01Email jpiontek@ump.edu.plPurpose: The poorly soluble nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA), was studied to maximize its solubility, permeability through biological membranes, and pharmacological activity.Methods: A mixture with magnesium stearate (MS) – microenvironment pH-modifier was prepared, as well as systems additionally containing incorporating substances methyl-β-cyclodextrin (M-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The identification of TA-MS-CD systems was confirmed using experimental methods: X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR) with the theoretical support. Apparent solubility study was performed using the paddle apparatus, while in vitro gastrointestinal tract (GIT) and blood-brain barrier (BBB) permeability were conducted by using PAMPA (Parallel Artificial Membrane Permeability Assay). The in vivo part of the study used the mouse nitroglycerin (NTG)-induced migraine pain model.Results: From practically insoluble substance, TA in TA-MS-M-β-CD system dissolved up to 80.13% ± 2.77%, and in TA-MS-HP-β-CD up to 92.39% ± 3.25% in 180 minutes. An increase in TA permeability was also obtained in the TA-MS-M-β-CD and TA-MS-HP-β-CD systems through GIT membranes (Papp values 2.057 x 10− 5 cm s− 1 and 2.091 x 10− 5 cm s− 1, respectively) and through BBB (Papp values 3.658 x 10− 5 cm s− 1 and 3.629 x 10− 5 cm s− 1, respectively). The enlargement of the solubility and permeability impacted analgesia. The dose 25 mg/kg of both TA-MS-HP-β-CD and TA-MS-M-β-CD was almost equally effective and only slightly less effective than the dose 50 mg/kg of pure TA. Both TA-MS-HP-β-CD and TA-MS-M-β-CD used at 50 mg/kg more effectively attenuated tactile allodynia in NTG-treated mice than the same dose of pure TA. None of TA forms influenced heat hyperalgesia.Conclusion: Increasing solubility of TA caused an increase of its analgesic effect in an animal model of migraine pain.Keywords: tolfenamic acid, migraine pain, cyclodextrins, permeability, gastrointestinal tract, blood-brain barrier

Apigenin (APG), a bioactive flavonoid with promising therapeutic potential, suffers from poor water solubility, which limits its bioavailability. To address this, solid dispersions of APG were prepared using ball milling with sodium alginate (SA), Pluronic ® F-68 (PLU68), Pluronic ® F-127 (PLU127), PVP K30, and PVP VA64 as polymeric excipients. These dispersions were screened for apparent solubility in water and buffers with pH 1.2, 5.5, and 6.8. Based on improved solubility after 60 min, APG-PLU68 and APG-PLU127 dispersions were selected for further study. DSC and FT-IR analysis confirmed molecular interactions between APG and the polymer matrices, contributing to enhanced solubility and dissolution rates. Dissolution rate studies showed that APG-PLU127 achieved 100% solubility at pH 6.8, suggesting its potential use in environments such as the small intestine. Additionally, APG-PLU127 exhibited 84.3% solubility at pH 1.2, indicating potential for solid oral dosage forms, where APG could be absorbed in the acidic conditions of the stomach. The stability study confirmed that storage for one year under ambient conditions does not cause chemical degradation but affects the physical state and solubility of the dispersion. Antioxidant activity was assessed using the ABTS assay. Freshly obtained APG-PLU127 showed 68.1% ± 1.94% activity, whereas APG-PLU127 stored for one year under ambient conditions exhibited 66.2% ± 1.62% (significant difference, p < 0.05). The difference was related to a slight decrease in the solubility of APG in the solid dispersion (T0 = 252 ± 1 μg∙mL -1 , T1 = 246 ± 1 μg∙mL -1 ). The findings demonstrate the superior performance of PLU127 as a carrier for enhancing the solubility, release, and antioxidant activity of APG.

In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit ® ) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit ® -HP-β-cyclodextrin) of fisetin (FIS) were prepared by the mechanochemical method without solvent. The amorphous nature of FIS in ASDs and ASIs was confirmed using XRPD (X-ray powder diffraction). DSC (Differential scanning calorimetry) confirmed full miscibility of multicomponent delivery systems. FT-IR (Fourier-transform infrared analysis) confirmed interactions that stabilize FIS's amorphous state and identified the functional groups involved. The study culminated in evaluating the impact of amorphization on water solubility and conducting in vitro antioxidant assays: 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-ABTS, 2,2-diphenyl-1-picrylhydrazyl-DPPH, Cupric Reducing Antioxidant Capacity-CUPRAC, and Ferric Reducing Antioxidant Power-FRAP and in vitro neuroprotective assays: inhibition of acetylcholinesterase-AChE and butyrylcholinesterase-BChE. In addition, molecular docking allowed for the determination of possible bonds and interactions between FIS and the mentioned above enzymes. The best preparation turned out to be ASI&#95;30&#95;EPO (ASD fisetin-Eudragit ® containing 30% FIS in combination with HP-β-cyclodextrin), which showed an improvement in apparent solubility (126.5 ± 0.1 µg∙mL -1 ) and antioxidant properties (ABTS: IC 50 = 10.25 µg∙mL -1 , DPPH: IC 50 = 27.69 µg∙mL -1 , CUPRAC: IC 0.5 = 9.52 µg∙mL -1 , FRAP: IC 0.5 = 8.56 µg∙mL -1 ) and neuroprotective properties (inhibition AChE: 39.91%, and BChE: 42.62%).

Our research aimed to develop an amorphous solid dispersion (ASD) of myricetin (MYR) with Polyvinylpyrrolidone K30 (PVP30) to enhance its solubility, dissolution rate, antioxidant, and neuroprotective properties. Employing a combination of solvent evaporation and freeze drying, we successfully formed MYR ASDs. XRPD analysis confirmed complete amorphization in 1:8 and 1:9 MYR-PVP weight ratios. DSC thermograms exhibited a single glass transition (Tg), indicating full miscibility. FT-IR results and molecular modeling confirmed hydrogen bonds stabilizing MYR's amorphous state. HPLC analysis indicated the absence of degradation products, ensuring safe MYR delivery systems. Solubility, dissolution rate (pH 1.2 and 6.8), antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays), and in vitro neuroprotective activities (inhibition of cholinesterases: AChE and BChE) were significantly improved compared to the pure compound. Molecular docking studies revealed that MYR had made several hydrogen, hydrophobic, and π-π stacking interactions, which could explain the compound's potency to inhibit AChE and BChE. MYR-PVP 1:9 w / w ASD has the best solubility, antioxidant, and neuroprotective activity. Stability studies confirmed the physical stability of MYR-PVP 1:9 w / w ASD immediately after dissolution and for two months under ambient conditions. Our study showed that the obtained ASDs are promising systems for the delivery of MYR with the potential for use in alleviating the symptoms of neurodegenerative diseases.

In this study, amorphous solid dispersions (ASDs) of pterostilbene (PTR) with polyvinylpyrrolidone polymers (PVP K30 and VA64) were prepared through milling, affirming the amorphous dispersion of PTR via X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Subsequent analysis of DSC thermograms, augmented using mathematical equations such as the Gordon-Taylor and Couchman-Karasz equations, facilitated the determination of predicted values for glass transition (T g ), PTR's miscibility with PVP, and the strength of PTR's interaction with the polymers. Fourier-transform infrared (FTIR) analysis validated interactions maintaining PTR's amorphous state and identified involved functional groups, namely, the 4'-OH and/or -CH groups of PTR and the C=O group of PVP. The study culminated in evaluating the impact of amorphization on water solubility, the release profile in pH 6.8, and in vitro permeability (PAMPA-GIT and BBB methods). In addition, it was determined how improving water solubility affects the increase in antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays) and neuroprotective (inhibition of cholinesterases: AChE and BChE) properties. The apparent solubility of the pure PTR was ~4.0 µg·mL -1 and showed no activity in the considered assays. For obtained ASDs (PTR-PVP30/PTR-PVPVA64, respectively) improvements in apparent solubility (410.8 and 383.2 µg·mL -1 ), release profile, permeability, antioxidant properties (ABTS: IC 50 = 52.37/52.99 μg·mL -1 , DPPH: IC 50 = 163.43/173.96 μg·mL -1 , CUPRAC: IC 0.5 = 122.27/129.59 μg·mL -1 , FRAP: IC 0.5 = 95.69/98.57 μg·mL -1 ), and neuroprotective effects (AChE: 39.1%/36.2%, BChE: 76.9%/73.2%) were confirmed.

Attenuated total reflection-Mid-Fourier transform-infrared (ATR-Mid-FT-IR) spectroscopy combined with principal component analysis (PCA) has been applied for the discrimination of amorphous solid dispersion (ASD) of kaempferol with different types of Eudragit (L100, L100-55, EPO). The ASD samples were prepared by ball milling. Training and test sets for PCA consisted of a pure compound, physical mixture, and incomplete/complete amorphous solid dispersion. The obtained results confirmed that the range 400-1700 cm -1 was the major contributor to the variance described by PC1 and PC2, which are the fingerprint region. The obtained PCA model selected fully amorphous samples as follows: five for KMP-EL100, two for KMP-EL100-55, and six for KMP-EPO (which was confirmed by the XRPD analysis). DSC analysis confirmed full miscibility of all ASDs (one glass transition temperature). FT-IR analysis confirmed the formation of hydrogen bonds between the -OH and/or -CH groups of KMP and the C=O group of Eudragits. Amorphization improved the solubility of kaempferol in pH 6.8, pH 5.5, and HCl 0.1 N.

Poor bioavailability hampers the use of curcumin and piperine as biologically active agents. It can be improved by enhancing the solubility as well as by using bioenhancers to inhibit metabolic transformation processes. Obtaining an amorphous system of curcumin and piperine can lead to the overcoming of these limitations. Hot-melt extrusion successfully produced their amorphous systems, as shown by XRPD and DSC analyses. Additionally, the presence of intermolecular interactions between the components of the systems was investigated using the FT-IR/ATR technique. The systems were able to produce a supersaturation state as well as improve the apparent solubilities of curcumin and piperine by 9496- and 161-fold, respectively. The permeabilities of curcumin in the GIT and BBB PAMPA models increased by 12578- and 3069-fold, respectively, whereas piperine's were raised by 343- and 164-fold, respectively. Improved solubility had a positive effect on both antioxidant and anti-butyrylcholinesterase activities. The best system suppressed 96.97 ± 1.32% of DPPH radicals, and butyrylcholinesterase activity was inhibited by 98.52 ± 0.87%. In conclusion, amorphization remarkably increased the dissolution rate, apparent solubility, permeability, and biological activities of curcumin and piperine.

The aim of our research was to improve the solubility and antioxidant activity of pterostilbene (PTR) by developing a novel amorphous solid dispersion (ASD) with Soluplus ® (SOL). DSC analysis and mathematical models were used to select the three appropriate PTR and SOL weight ratios. The amorphization process was carried out by a low-cost and green approach involving dry milling. An XRPD analysis confirmed the full amorphization of systems in 1:2 and 1:5 weight ratios. One glass transition (T g ) observed in DSC thermograms confirmed the complete miscibility of the systems. The mathematical models indicated strong heteronuclear interactions. SEM micrographs suggest dispersed PTR within the SOL matrix and a lack of PTR crystallinity, and showed that after the amorphization process, PTR-SOL systems had a smaller particle size and larger surface area compared with PTR and SOL. An FT-IR analysis confirmed that hydrogen bonds were responsible for stabilizing the amorphous dispersion. HPLC studies showed no decomposition of PTR after the milling process. PTR's apparent solubility and antioxidant activity after introduction into ASD increased compared to the pure compound. The amorphization process improved the apparent solubility by ~37-fold and ~28-fold for PTR-SOL, 1:2 and 1:5 w / w , respectively. The PTR-SOL 1:2 w / w system was preferred due to it having the best solubility and antioxidant activity (ABTS: IC 50 of 56.389 ± 0.151 µg·mL -1 and CUPRAC: IC 0.5 of 82.52 ± 0.88 µg·mL -1 ).

Oleanolic (OA) and glycyrrhetinic acids (GE), as well as their derivatives, show a variety of pharmacological properties. Their crystal structures provide valuable information related to the assembly modes of these biologically active compounds. In the known-to-date crystals of OA esters, their 11-oxo derivatives, and GE ester crystals, triterpenes associate, forming different types of ribbons and layers whose construction is based mainly on van der Waals forces and weak C-H···O interactions. New crystal structures of 11-oxo OA methyl ester and the polymorph of OA butyl ester reveal an alternative aggregation mode. Supramolecular architectures consist of helical chains which are stabilized by hydrogen bonds of O-H···O type. It was found that two polymorphic forms of butyl OA ester (layered and helical) are related monotropically. In a structure of metastable form, O-H···O hydrogen bonds occur, while the thermodynamically preferred phase is governed mainly by van der Waals interactions. The intermolecular interaction energies calculated using CrystalExplorer, PIXEL, and Psi4 programs showed that even in motifs formed through O-H···O hydrogen bonds, the dispersive forces have a significant impact.

The objective of this study was to obtain co-amorphous systems of poorly soluble sinapic acid using amino acids as co-formers. In order to assess the probability of the interaction of amino acids, namely, arginine, histidine, lysine, tryptophan, and proline, selected as co-formers in the amorphization of sinapic acid, in silico studies were carried out. Sinapic acid systems with amino acids in a molar ratio of 1:1 and 1:2 were obtained using ball milling, solvent evaporation, and freeze drying techniques. X-ray powder diffraction results confirmed the loss of crystallinity of sinapic acid and lysine, regardless of the amorphization technique used, while remaining co-formers produced mixed results. Fourier-transform infrared spectroscopy analyses revealed that the co-amorphous sinapic acid systems were stabilized through the creation of intermolecular interactions, particularly hydrogen bonds, and the potential formation of salt. Lysine was selected as the most appropriate co-former to obtain co-amorphous systems of sinapic acid, which inhibited the recrystallization of sinapic acid for a period of six weeks in 30 °C and 50 °C. Obtained co-amorphous systems demonstrated an enhancement in dissolution rate over pure sinapic acid. A solubility study revealed a 12.9-fold improvement in sinapic acid solubility after introducing it into the co-amorphous systems. Moreover, a 2.2-fold and 1.3-fold improvement in antioxidant activity of sinapic acid was observed with respect to the ability to neutralize the 2,2-diphenyl-1-picrylhydrazyl radical and to reduce copper ions, respectively.

Despite the recent dynamic development of medicine, influenza is still a significant epidemiological problem for people around the world. The growing resistance of influenza viruses to currently available antiviral drugs makes it necessary to search for new compounds or drug forms with potential high efficacy against human influenza A and B viruses. One of the methods of obtaining new active compounds is to chemically modify privileged structures occurring in the natural environment. The second solution, that is gaining more and more interest, is the use of modern drug carriers, which significantly improve physicochemical and pharmacokinetic parameters of the transported substances. Molecules known from the earliest times for their numerous therapeutic properties are glycyrrhizinic acid (GA) and glycyrrhetinic acid (GE). Both compounds constitute the main active agents of the licorice (Glycyrrhiza glabra, Leguminosae) root and, according to a number of scientific reports, show antiviral properties against both DNA and RNA viruses. The above information prompted many scientific teams around the world to obtain and test in vitro and/or in vivo new synthetic GA and GE derivatives against influenza A and B viruses. Similarly, in recent years, a significant amount of GA and GE-based drug delivery systems (DDS) such as nanoparticles, micelles, liposomes, nanocrystals, and carbon dots has been prepared and tested for antiviral activity, including those against influenza A and B viruses. This work systematizes the attempts undertaken to study the antiviral activity of new GA and GE analogs and modern DDS against clinically significant human influenza viruses, at the same time indicating the directions of their further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The present study reports amorphous solid dispersions (ASDs) of hesperidin (Hes) prepared by ball milling to improve its solubility and apparent solubility over the unmodified compound. The carriers were Soluplus ® (Sol), alginate sodium (SA), and hydroxypropylmethylcellulose (HPMC). XRPD analysis confirmed full amorphization of all binary systems in 1:5 w/w ratio. One glass transition (T g ) observed in DSC thermograms of hesperidin:Soluplus ® (Hes:Sol) and hesperidin:HPMC (Hes:HPMC) 1:5 w/w systems confirmed complete miscibility. The mathematical model (Gordon-Taylor equation) indicates that the obtained amorphous systems are characterized by weak interactions. The FT-IR results confirmed that hydrogen bonds are responsible for stabilizing the amorphous state of Hes. Stability studies indicate that the strength of these bonds is insufficient to maintain the amorphous state of Hes under stress conditions (25 °C and 60 °C 76.4% RH). HPLC analysis suggested that the absence of degradation products indicates safe hesperidin delivery systems. The solubility and apparent solubility were increased in all media (water, phosphate buffer pH 6.8 and HCl (0.1 N)) compared to the pure compound. Our study showed that all obtained ASDs are promising systems for Hes delivery, wherein Hes:Sol 1:5 w/w has the best solubility (about 300-fold in each media) and apparent solubility (about 70% in phosphate buffer pH 6.8 and 63% in HCl).

Iron(III) porphyrazines containing peripheral 2,5-dimethyl-, 2-methyl-5-phenyl-, and 2,3,5-triphenyl-1 H -pyrrol-1-yl substituents were synthesized and subjected to physicochemical characterization. This was accomplished by high-resolution mass spectrometry, nuclear magnetic resonance (as diamagnetic Fe(II) derivatives), HPLC purity analysis, and UV-Vis spectroscopy, accompanied by the solvation study in dichloromethane and pyridine. X-ray structure analysis was performed for a single crystal of the previously obtained 2,5-diphenyl-substituted derivative of porphyrazine complex ( 5d ). The octahedral geometries of iron cation, present in the porphyrazine core, influenced the packing mode of molecules in the crystals. Mössbauer studies, performed for solid samples of iron porphyrazines, indicated that low-spin reduced iron states might occupy low- or high-symmetry binding sites. It was found that the hyperfine parameters and the subsequent contribution of the iron cations depend on the number of phenyl groups surrounding the pyrrolyl moiety. For iron(II) porphyrazine 2,3,5-triphenylpyrrol-1-yl substituents ( 5b ), a high-spin ferrous state fraction was observed. Temperature-dependent measurements showed that the freed rotation of the peripheral porphyrazine ligands and the increased flexibility of the macrocycle ring result in the Fe 2+ ion being stabilized in a diamagnetic state at a binding site of high symmetry at room temperature in the solid state. This process is most probably stimulated by the range of collective motions of the polymeric ribbons consisting of iron(II) porphyrazines observed in the X-ray.

Magnesium(II) sulfanyl porphyrazine with peripheral morpholinethoxy substituents was embedded on the surface of titanium(IV) dioxide nanoparticles. The obtained nanocomposites were characterized with the use of particle size and distribution (NTA analysis), electron microscopy (SEM), thermal analysis (TGA), FTIR-ATR spectroscopy, and X-ray powder diffraction (XRD). The measured particle size of the obtained material was 327.4 ± 15.5 nm. Analysis with XRD showed no visible changes in the crystallinity of the material after deposition of porphyrazine on the TiO 2 surface. However, SEM images revealed noticeable changes in the morphology of the obtained hybrid material: higher aggregation and less ordered structure of the aggregates. The TGA analysis revealed the lost 3.6% (0.4 mg) of the mass of obtained material in the range 250-550 °C. In the FTIR-ATR analysis, C-H stretching vibratins in the range of 3000-2800 cm -1 , originating from porphyrazine moieties, were detected. The photocatalytic applicability of the nanomaterial was assessed in photodegradation studies of methylene blue and bisphenol A as reference environmental pollutants. In addition, the photocatalytic degradation of carbamazepine with porphyrazine/TiO 2 hybrids as photocatalysts was studied, accompanied by an HPLC chromatography assessment of photodegradation. In total, 43% of the initial concentration was achieved in the case of bisphenol A, after 4 h of irradiation, whereas 57% was achieved in the case of carbamazepine. In each photodegradation reaction, the activity of the obtained photocatalytic nanomaterial was proved with almost linear degradation. The photodegradation reaction rate constants were calculated, and revealed 5.75 × 10 -5 s -1 for bisphenol A and 5.66 × 10 -5 s -1 for carbamazepine.

Rosmarinic acid (RA) is a natural antioxidant with neuroprotective properties; however, its preventive and therapeutic use is limited due to its slight solubility and poor permeability. This study aimed to improve RA physicochemical properties by systems formation with cyclodextrins (CDs): hydroxypropyl-α-CD (HP-α-CD), HP-β-CD, and HP-γ-CD, which were prepared by the solvent evaporation (s.e.) method. The interactions between components were determined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier Transform infrared spectroscopy (FTIR). The sites of interaction between RA and CDs were suggested as a result of in silico studies focused on assessing the interaction between molecules. The impact of amorphous systems formation on water solubility, dissolution rate, gastrointestinal (GIT) permeability, and biological activity was studied. RA solubility was increased from 5.869 mg/mL to 113.027 mg/mL, 179.840 mg/mL, and 194.354 mg/mL by systems formation with HP-α-CD, HP-β-CD, and HP-γ-CD, respectively. During apparent solubility studies, the systems provided an acceleration of RA dissolution. Poor RA GIT permeability at pH 4.5 and 5.8, determined by parallel artificial membrane permeability assay (PAMPA system), was increased; RA-HP-γ-CD s.e. indicated the greatest improvement (at pH 4.5 from P app 6.901 × 10 -7 cm/s to 1.085 × 10 -6 cm/s and at pH 5.8 from 5.019 × 10 -7 cm/s to 9.680 × 10 -7 cm/s). Antioxidant activity, which was determined by DPPH, ABTS, CUPRAC, and FRAP methods, was ameliorated by systems; the greatest results were obtained for RA-HP-γ-CD s.e. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was increased from 36.876% for AChE and 13.68% for BChE to a maximum inhibition of the enzyme (plateau), and enabled reaching IC 50 values for both enzymes by all systems. CDs are efficient excipients for improving RA physicochemical and biological properties. HP-γ-CD was the greatest one with potential for future food or dietary supplement applications.

Synthesis and structural characterization of new esters of oleanolic acid and its 11-oxo derivatives are reported. Compounds crystallize in four isostructural groups, each containing one to four structures. Single-crystal X-ray analysis revealed that molecules belonging to non-isostructural groups self-associate according to two schemes that describe also supramolecular architectures in crystals of glycyrrhetinic acid derivatives. Structural motifs arise as a result of van der Waals forces. Parameters introduced for the analysis of one- and two-dimensional assemblies allow the comparison of motifs in isostructural and non-isostructural crystals, including polymorphs, and a qualitative assessment of differences in molecular self-assembly. One-, two- or three-dimensional similarity has been confirmed by XPac calculations.

Due to the destruction of the integrity of the parent crystal, single-crystal-to-single-crystal phase transition in organic compounds is still a relatively rare phenomenon. The phase transition in glycyrrhetinic acid isopropyl ester is triggered by temperature change. The increasing volume of the isopropyl substituent as a result of increasing temperature forces a remodelling of the structural motifs. These changes cause a single-crystal-to-single-crystal phase transition. The low-temperature form is isostructural with glycyrrhetinic acid methanol solvate, while the high-temperature phase is isostructural with the ethyl ester of this acid.

Newly developed tetra- and octasubstituted methimazole-phthalocyanine conjugates as potential photosensitizers have been obtained. Synthesized intermediates and final products were characterized by the MALD-TOF technique and various NMR techniques, including 2D methods. Single-crystal X-ray diffraction was used to determine the crystal structures of dinitriles. The studied phthalocyanines revealed two typical absorption bands-the Soret band and the Q band. The most intense fluorescence was observed for octasubstituted magnesium(II) phthalocyanine in DMF (Φ FL = 0.022). The best singlet oxygen generators were octasubstituted magnesium(II) and zinc(II) phthalocyanines (Φ ∆ 0.56 and 0.81, respectively). The studied compounds presented quantum yields of photodegradation at the level between 10 -5 and 10 -6 . Due to their low solubility in a water environment, the liposomal formulations were prepared. Within the studied group, octasubstituted zinc(II) phthalocyanine at the concentration of 100 µM activated with red light showed the highest antibacterial activity against S. aureus equal to a 5.68 log reduction of bacterial growth.