Characterization of the interaction between a platinum(II) complex and human serum albumin: spectroscopic analysis and molecular docking

In this study, the interaction between (2,2?-bipyridine)(pyrrolidinedithiocarbamato) platinum(II) nitrate, [Pt(bpy)(pyr-dtc]NO₃, and human serum albumin (HSA) was investigated by various spectroscopic methods (UV–vis, fluorescence, CD and FT-IR) and molecular docking technique at three temperatures. UV–vis absorption spectroscopy showed that Pt(II) complex can denature the protein at moderate concentrations. The results of emission quenching at two temperatures has revealed that the quenching mechanism of Pt(II) complex with HSA was static quenching mechanism. Binding constants (K), binding site number (n) and corresponding thermodynamic parameters ?G?, ?H? and ?S? were calculated and revealed that hydrophobic forces played a major role when Pt(II) complex interacted with HSA. The binding distance (r) between above complex and HSA based on Förster?s theory of non-radiation energy transfer was calculated as 3.22 nm. Alterations of HSA secondary structure induced by complex were confirmed by FT-IR and CD measurements. Also, a molecular docking study was performed for identification of key structural features of binding of the Pt complex into the receptor and predicting bioactive conformers. Our results may provide valuable information to understand the mechanistic pathway of drug delivery and to pharmacological behavior of drug.     

Chlorofluorofullerenes (CFFs)

We have applied density functional theory calculations to devise stable arrangements of chlorofluorofullerenes (CFFs). In the case of C₆₀ClF and C₆₀Cl₂F₂, an extensive isomer search shows that the most stable configurations are those with two halogens located on the corannulene-like structure. In general, 1,2-adduct is more stable than 1,4-adduct and 1,2 addition across 6–6 bonds is more stable than 1,2 addition across 5–6 bonds. The formation of a CFF from chlorofullerene is exothermic while chlorination of a fluorofullerene is endothermic. For C₆₀Cl_18-3nF_3n (n = 0, 1, 2, 3, 4, 5, and 6), the binding energies decrease as the number of Cl atoms increases and the energy differences between isomers with the same formula are small. The ¹³C NMR patterns of C₆₀Cl_18-3nF_3n (n = 0, 1, 2, 3, 4, 5, and 6) are divided into two parts: δ_iso values of chlorinated and fluorinated carbons shift to low field and appear in the range of 65.1–100.2 and 84.5–97.4 ppm; two peaks related to C sites on the cyclohexatriene pole and the flattened equatorial belt separating the two hemispheres appear at 120.2–123.4 and 125.8–129.1 ppm, respectively. Negative nucleus independent chemical shift (NICS) in interior positions of rings or cages indicates the presence of induced diatropic ring currents which suggests that cyclohexatriene poles can be considered as benzenoid fragments. NICS yields minor value (?2.7 ppm) at the ring center of polar pentagons of C₆₀Cl₁₀F₁₀, and significantly negative values in the cage center.     

Straightforward synthesis of thiazoline-incorporated chalconoids from phenacyl halides

A series of thiazoline-incorporated chalconoids, designed based on natural product scaffold, were efficiently synthesized via the reaction of 3-methyl-4-arylthiazole-2(3 $H$ )-thiones and appropriate phenacyl halides, and subsequent desulfurization. The starting 3-methyl-4- arylthiazole-2(3 $H$ )-thiones were also prepared from phenacyl halides. The structural aspects and ( $Z$ )-geometry of compounds were confirmed by IR and $^{1}$ H NMR spectral data. This chemistry provides a new library of compounds basically originated from phenacyl halides as building blocks, with potential activity for biomedical screening.     

Highly cis‐Diastereoselective Synthesis of Coumarin‐Based 2,3‐Disubstituted Dihydrobenzothiazines by Organocatalysis

An efficient and organocatalyzed asymmetric reaction of phenacyl halides with coumarin‐based dihydrobenzothiazoles was developed to afford cis‐2,3‐disubstituted 3,4‐dihydro‐2H‐benzothiazines. This method provides a one‐step and highly diastereoselective route to a wide variety of coumarin‐based 3,4‐dihydro‐2H‐benzothiazines using the cheap and commercially available Cinchona alkaloid quinine hydrochloride.     

Preparation and Characterization of Agarose-Gelatin Blend Hydrogels as a Cell Encapsulation Matrix: An In-Vitro Study

Cell encapsulation represents an alternative nonviral technique to treat multiple diseases, leading to a reduction or even absence of administration of immunosuppressants. Hydrogels have been introduced as novel materials suitable for cell encapsulation. This study involves agarose–gelatin blend hydrogels with four different weight percentage ratios (100:0, 75:25, 50:50, 25:75) of agarose to gelatin. Prepared blend hydrogels were assessed in terms of rheological behavior (gel point by using complex viscosity), cell attachment (hemocytometer), cell viability and cytotoxicity (3-(3,4-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliium bromide, MTT assay), and mechanical and integral stability (Bradford test and shear force rupture assay, respectively). Based on the obtained rheological experimental results, the sol-gel transition point for 50:50 was in the physiological condition range (35°C–37°C). The percent of nonattached cells on the surface of the hydrogel decreased from 92% for the 100:0 sample to 46.3% for the 50:50 sample, and the cell viability was more than 95%. A good structural integrity was achieved for samples with weight ratio of 50:50; 20.195% gelatin was released during the 24 h in phosphate buffer solution at 25°C and the mechanical stability of agarose–gelatin microcapsules under shear force were improved about 14% rather than pure agarose microcapsule.     

Chemistry of aqueous silica nanoparticle surfaces and the mechanism of selective peptide adsorption

Control over selective recognition of biomolecules on inorganic nanoparticles is a major challenge for the synthesis of new catalysts, functional carriers for therapeutics, and assembly of renewable biobased materials. We found low sequence similarity among sequences of peptides strongly attracted to amorphous silica nanoparticles of various size (15-450 nm) using combinatorial phage display methods. Characterization of the surface by acid base titrations and zeta potential measurements revealed that the acidity of the silica particles increased with larger particle size, corresponding to between 5% and 20% ionization of silanol groups at pH 7. The wide range of surface ionization results in the attraction of increasingly basic peptides to increasingly acidic nanoparticles, along with major changes in the aqueous interfacial layer as seen in molecular dynamics simulation. We identified the mechanism of peptide adsorption using binding assays, zeta potential measurements, IR spectra, and molecular simulations of the purified peptides (without phage) in contact with uniformly sized silica particles. Positively charged peptides are strongly attracted to anionic silica surfaces by ion pairing of protonated N-termini, Lys side chains, and Arg side chains with negatively charged siloxide groups. Further, attraction of the peptides to the surface involves hydrogen bonds between polar groups in the peptide with silanol and siloxide groups on the silica surface, as well as ion-dipole, dipole-dipole, and van-der-Waals interactions. Electrostatic attraction between peptides and particle surfaces is supported by neutralization of zeta potentials, an inverse correlation between the required peptide concentration for measurable adsorption and the peptide pI, and proximity of cationic groups to the surface in the computation. The importance of hydrogen bonds and polar interactions is supported by adsorption of noncationic peptides containing Ser, His, and Asp residues, including the formation of multilayers. We also demonstrate tuning of interfacial interactions using mutant peptides with an excellent correlation between adsorption measurements, zeta potentials, computed adsorption energies, and the proposed binding mechanism. Follow-on questions about the relation between peptide adsorption on silica nanoparticles and mineralization of silica from peptide-stabilized precursors are raised.     

Synthesis and antibacterial activity of N-[2-(2-naphthyl)ethyl]piperazinyl quinolones

A series of N-[2-(2-naphthyl)ethyl]piperazinyl quinolones containing a carbonyl related functional groups (oxo- or oxyimino-) on the ethyl spacer was synthesized and evaluated for antibacterial activity. The synthesis of N-[2-(2-naphthyl)ethyl]piperazinyl quinolones was achieved through the versatile and efficient synthetic route that involved reaction of piperazinyl quinolones with appropriate α-bromoketone or α-bromooxime derivatives. The structures of new compounds were confirmed by elemental analysis, IR and NMR spectra. Antibacterial data indicated that some of the new N-[2-(2-naphthyl)ethyl]piperazinyl quinolones showed good antibacterial activity and modification of the position 8 and N-1 substituent on quinolone ring, and ethyl spacer functionality produced significant changes in activity against Gram-positive and Gram-negative bacteria.     

Sesquiterpene lactones from Centaurea rhizantha C.A. Meyer

Two new sesquiterpene lactones, rhizantholide A (1) and rhizantholide B (2), together with five known compounds (3-7) have been isolated from the aerial parts of Centaurea rhizantha (Asteraceae). Sesquiterpene lactones belong to guaianolide class, and rhizantholide B is a rare guaianolide characterized by a free primary alcoholic function at C-10 along with a 3β,10β-epoxy function. Their structures have been established on the basis of 1D and 2D NMR experiments, as well as HR-ESIMS. The antimicrobial activity of compounds 1-7 has been evaluated against Gram-positive and Gram-negative strains. Only deacylcynaropicrin 8-O-[3′-hydroxy-2′-methylpropionate] (5) showed moderate antibacterial activity against Staphylococcus aureus with a MIC/MBC value of 500 μg/mL. All isolated compounds have been also evaluated for their cytotoxic activities against cancer cells. Among them, compound 5 showed the highest cytotoxic activity with IC₅₀ values in the range 5.02–16.76 μg/mL.