Sevgi Sarigul Ozbek

Photodynamic therapy has been considered a suitable alternative to chemotherapy in recent years. In this method, a photosensitizing agent is activated by light, converting triplet oxygen molecules into singlet oxygen, which is required for the elimination of cancerous tissues. This study reports the synthesis of a new phthalonitrile derivative (1), namely 4-chloro-5-(4-(trifluoromethoxy)phenoxy)phthalonitrile. Its structural characterization was performed using 1H nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy. Zinc (II) phthalocyanine (ZnPc) was synthesized by cyclotetramerization of compound (1) in the presence of the zinc ion. Its characterization was performed using ¹H NMR, FT-IR, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), and ultraviolet-visible (UV-vis) spectroscopy. The electronic absorption spectra of the macromolecule (ZnPc) were recorded at different concentrations in various solvents to study the effects of concentration and solvent nature on its aggregation behavior. The efficiency of zinc (II) phthalocyanine in photodynamic therapy was evaluated by measuring its singlet-oxygen quantum yield. The macromolecule exhibited high solubility at the studied concentration in ethanol, dichloromethane, and dimethyl sulfoxide. Additionally, its singlet-oxygen quantum yield was calculated to be 0.81, higher than that of the unsubstituted zinc (II) phthalocyanine.

Objective: Recently, phthalocyanines have been of interest in therapeutic applications owing to the discovery of their outstanding biological activities (especially efficient DNA interactions). Therefore, this study reports the preparation of a new hexadeca-substituted manganese (III) phthalocyanine (MnPc) and its water-soluble derivative (QMnPc).Materials and Methods: MnPc, bearing hexyloxy, aminated, and fluorinated groups, was synthesized via a one-step metal template mechanism and then converted into its water-soluble form by treating it with iodomethane. The phthalocyanines were characterized using Fourier-transform infrared (FT-IR) and ultraviolet visible (UV-vis) spectroscopies. Additionally, the interaction between the macromolecule QMnPc and the DNA molecule was studied using a UV-vis spectrophotometer at 310 and 338 Kelvin.Results: As DNA concentration increased, the absorbance decreased, accompanied by a bathochromic shift. This observation confirmed that the studied phthalocyanine interacted with the DNA molecule via non-bonding mechanisms (intercalation and electrostatic attraction). Moreover, the binding mode was examined by obtaining the thermodynamic parameters (entropy change (∆S)>0, enthalpy change (∆H)<0, and Gibbs free energy change (∆G)<0).Conclusion: The computed positive ΔS, as well as the negative values of ΔG and ΔH, confirmed that the DNA-QMnPc interaction was spontaneous and thermodynamically favored. Therefore, macromolecule QMnPc can be considered a promising agent for medical applications.

Cisplatin is a widely used chemotherapeutic agent, and its precise & accurate quantification in solutions is crucial because these methods could be further used for its determination in pharmaceutical formulations and biological matrices. Here, a novel, rapid, and reliable reversed-phase isocratic HPLC method was developed and validated for the determination of cisplatin in solution. The resolution was achieved using a C18 column as the stationary phase and a mixture of methanol:sodium dodecyl sulphate (MeOH:SDS, 0.5 mM, 30:70) with a flow rate of 0.5 mL/min as the mobile phase. The detection was carried out at 204 nm, and the analysis was completed within seven minutes. The validation of the proposed method, which is easy, fast, and does not require the use of any acid or base, was performed in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals (ICH Q2(R2)). Depending on the findings, the developed method showed high linearity over the concentration range of 20-150 μg/mL. The limit of detection (LOD) and limit of quantitation (LOQ) were determined to be 7.37 and 22.33 μg/mL, respectively. Compared with previously reported methods, the proposed method demonstrated superior performance, with a wider linear range and acceptable LOD and LOQ. The system suitability parameters, including retention time, number of plates, height equivalent of a theoretical plate (HETP), area, tailing, and resolution, were evaluated. According to the obtained results, the developed method showed excellent chromatographic performance, characterized by high resolution, acceptable tailing, and a short analysis time.

2‐Thiohydantoin derivatives, including different substitutions at N‐1 and C‐5 (5‐methyl‐, 5‐isopropyl‐, 1‐acetyl‐5‐methyl‐, and 1‐acetyl‐5‐isopropyl‐) (1–4, respectively), were synthesized by the known literature methods. In these synthetic pathways, it was reported that enantiomerically pure 2‐thiohydantions were obtained in the absence of any solvent via the reaction of L‐amino acids with thiourea (1&2) and via the reaction of L‐amino acids with NH₄SCN and acetic anhydride (3&4). However, in this study, in contrary to the previous literature studies, racemic mixtures of 2‐thiohydantoins were obtained although the same synthetic methods were used. The racemic nature of 2‐thiohydantoin derivatives (1–4) was proved by using ¹H NMR analysis in the presence of (1R,2S)‐(−)‐ephedrine as a chiral auxiliary. In addition, the enantiomers of 3&4 were also resolved on chiral stationary phases by HPLC analyses. Furthermore, newly synthesized unsymmetrical chiral thioureas (S‐1&S‐2) and previously synthesized symmetrical ones (SS‐3&SS‐4) were used as chiral solvating agent (CSA) for the enantiodiscrimination of the thiohydantoins (5&6), previously reported. Optimal CSA/substrate ratios were determined for the best enantiodiscrimination.

In materials science, chiral perovskites stand out due to their exceptional optoelectronic properties and the versatility in their structure and composition, positioning them as crucial in the advances of technologies in spintronics and chiroptical systems. This review underlines the critical role of synthesizing and growing these materials, a process integral to leveraging their complex interplay between structural chirality and distinctive optoelectronic properties, including chiral-induced spin selectivity and chiroptical activity. The paper offers a comprehensive summary and discussion of the methods used in the synthesis and growth of chiral perovskites, delving into extensive growth techniques, fundamental mechanisms, and strategic approaches for the engineering of low-dimensional perovskites, alongside the creation of novel chiral ligands. The necessity of developing new synthetic approaches and maintaining precise control during the growth of chiral perovskites is emphasized, aiming to enhance their structural chirality and boost their efficiency in spin and chiroptical selectivity.

Stable, nonracemic axially chiral hemiaminals (O,N‐hemiacetals) have been synthesized stereoselectively from lithium aluminum hydride (LiAlH₄) reductions of nonracemic 5‐methyl‐ and 5‐isopropyl‐3‐(o‐aryl)‐2‐thioydantoins in tetrahydrofuran (THF) at room temperature in 10 min. PredominantlyS‐configured hemiaminals at C‐4 of the heterocyclic ring were produced from the S‐configured thiohydantoins at C‐5 (by 80% when the C5 substituent is methyl and by 97% when it is isopropyl). The configuration at C‐5 was retained during the reduction reaction. The stereochemical outcome of the axially chiral hemiaminals resulted from their conformational preferences.

Recently, Sarigul and Dogan have synthesized a number of enantiomerically enriched axially chiral atropoisomeric 2-thiohydantoins by the reaction of L-amino acid ester salts and o-aryl isothiocyanates in the presence of triethyl amine (TEA) in dichloromethane. The non-axially chiral derivative 5-methyl-3-phenyl-2-thiohydantoin gave a racemic product whereas the axially chiral 5-methyl-3-o-bromophenyl-2-thiohydantoin was less prone to racemize at C₅ of the heterocyclic ring. In this study, we present a computational study (M06-2X/6-311+G(d,p) for C, H, O, N and S; M06-2X/6-311++G(3df,3pd) for Br) in order to propose plausible mechanisms for the racemization and cyclization steps for 2-thiohydantoin derivatives. The study includes rationalization based on steric as well as the electrostatic effects to elucidate the epimerization differences at C₅.

A new racemic pyrazoline derivative was synthesized and resolved to its enantiomers using analytic and semipreparative high‐pressure liquid chromatography. The absolute configuration of both fractions was established using vibrational circular dichroism. The in vitro monoamine oxidase (MAO) inhibitory profiles were evaluated for the racemate and both enantiomers separately for the two isoforms of the enzyme. The racemic compound and both enantiomers were found to inhibit hMAO‐A selectively and competitively. In particular, the R enantiomer was detected as an exceptionally potent and a selective MAO‐A inhibitor ( K _i = 0.85 × 10 ⁻³ ± 0.05 × 10 ⁻³ μM and SI: 2.35 × 10 ⁻⁵ ), whereas S was determined as poorer compound than R in terms of K _i and SI (0.184 ± 0.007 and 0.001). The selectivity of the enantiomers was explained by molecular modeling docking studies based on the PDB enzymatic models of MAO isoforms.

Nonracemic axially chiral thiohydantoins were synthesized atroposelectively by the reaction of ortho-arylisothiocyanates with amino acid ester salts in the presence of triethylamine (TEA). The synthesis of the nonaxially chiral derivatives however gave thiohydantoins racemized at C-5 of the heterocyclic ring. The micropreparatively resolved enantiomers of the nonaxially chiral derivatives from the racemic products were found to be optically stable under neutral conditions. On formation of the 5-methyl-3-aryl-thiohydantoin ring, bulky ortho-aryl substituents at N3 were found to suppress the C-5 racemization and in this way enabled the transfer of chirality from the alpha-amino acid to the products. The corresponding 5-isopropyl thiohydantoins turned out to be more prone to racemization at C-5 during the ring formation. The isomer compositions of the synthesized axially chiral thiohydantoins have been determined through HPLC analyses with chiral stationary phases. In most cases a high prevalence of the P isomers over the M isomers has been obtained. The barriers to rotation determined around the N(sp2)-C(aryl) chiral axis were found to be dependent upon the size of the ortho-halo aryl substituents.