Fluorescence Emission Spectroscopy Research Articles

Classifying PDO Kalamata Olive Oil from Geographic Origins of the Messenia Region based on Statistical Machine Learning

Kalamata is a smart city located in southeastern Greece in the Mediterranean basin and it is the capital of the Messenia regional unit. It is known for the famous Protected Designation of Origin (PDO) Kalamata olive oil produced mainly from the Koroneiki olive variety. The PDO Kalamata olive oil, established by Council regulation (EC) No 510/2006, owes its quality and special characteristics to the geographical environment, olive tree variety, and human factor. The PDO Kalamata olive oil is produced exclusively in the regional unit of Messenia, being the main profit of local farmers. However, soil chemical composition, microclimates, and agronomic factors are changed within the Messenia spatial area leading to differentiation of PDO Kalamata olive oil characteristic. In this paper, we use statistical machine learning algorithms to determine the geographical origin of Kalamata olive oil at PDO level based on synchronous excitation−emission fluorescence spectroscopy of olive oils. Evaluations of the statistical models are promising for differentiating the origin of PDO Kalamata olive oil with high values of prediction accuracy thus enabling companies that process and bottle kalamata olive oil to choose olive oil from a specific region of Messenia that fulfills certain characteristics. Concretely, the current research effort focuses on a specific olive oil variety within a limited geographic region. Intuitively, future research should also focus on validation of the proposed methodology to other olive oil varieties and production areas.

Optimizing Green Synthesis of Hydrotalcite - Silver Nanoparticles using Syzygium Nervosum based Reducing Agent.

This work aimed to assess the effect of Syzygium nervosum leaf extract as a reducing agent for green synthesis of AgNPs on HT through an optimizing process using response surface methodology (RSM) and the Box-Benken model. The optimal conditions for synthesis of AgNPs on HT include reaction time of 6.15 hours, reaction temperature of 50 oC and the ratio of diluted Syzygium nervosum leaf extract to reduce AgNO3 of 50.37 mL/mg. Under the optimal conditions, the yield of reduction reaction reached 77.54 %, close to the theoretical value of 76.97 %.Besides, the morphology, density, and characteristics of AgNPs on the surface of HT layers have been determined by using Ultraviolet-visible spectroscopy, Field emission scanning electron microscopy, High resolution transmission electron microscopy, selected area diffraction, X-ray diffraction, Dynamic light scattering, Infraredspectroscopy, Fluorescence emission spectroscopy, Brunauer-Emmett-Teller methods. The spherical AgNPs were synthesized successfully on the surface of HT with the average particle size of 13.0 ± 1.1 nm. Interestingly, HT-Ag hybrid materials can inhibit strongly the growth of E. coli, S. aureus as well as two antibiotic resistance bacterial strains, P. stutzeri B27 and antibiotic resistance E. coli. Overall, the HT-Ag hybrid materials are very promising for application in practice.

Synthesis, characterization, biological potency, and molecular docking of Co2+, Ni2+ and Cu2+ complexes of a benzoyl isothiocyanate based ligand

The primary objective of the present study was to produce metal complexes of H4DAP ligand (N,N'-((pyridine-2,6-diylbis(azanediyl))bis(carbonothioyl))dibenzamide) derived from 2,6-diaminopyridine and benzoyl isothiocyanate with either ML or M2L stoichiometry. There are three distinct coordination complexes obtained with the formulas [Co(H2DAP)]·H2O, [Ni2(H2DAP)Cl2(H2O)2]·H2O, and [Cu(H4DAP)Cl2]·3H2O. The confirmation of the structures of all derivatives was achieved through the utilization of several analytical techniques, including FT-IR, UV–Vis, NMR, GC–MS, PXRD, SEM, TEM analysis, and QM calculations. Aiming to analyze various noncovalent interactions, topological methods such as QTAIM, NCI, ELF, and LOL were performed. Furthermore, the capacity of metal–ligand binding was examined by fluorescence emission spectroscopy. An in vitro investigation showed that the viability of MDA-MB-231 and HepG-2 cells was lower when exposed to the manufactured Cu2+ complex, in comparison to the normal cis-platin medication. The compounds were further evaluated for their in vitro antibacterial activity. The Ni2+ complex has shown promising activity against all tested pathogens, comparable to the reference drugs Gentamycin and Ketoconazole. Furthermore, a computational docking investigation was conducted to further examine the orientation, interaction, and conformation of the recently created compounds on the active site of the Bcl-2 protein.

Construction of Spin Crossover‐Fluorescent Bifunctional Cyclic Chain‐Like Fe(II) Compounds from Carbazole Ligands

The incorporation of fluorescent properties into spin‐crossover (SCO) materials, aiming at controlling fluorescence via spin‐state transitions for applications in magneto‐optical switching and information processing, represents an appealing research direction. In this study, we prepared two examples of one‐dimensional cyclic chain‐like Fe(II) coordination polymers, denoted as [Fe(DPPC)2(NCS)2]⋅CH3OH⋅o‐C6H4Cl2 (1, DPPC = 3,6‐di‐4‐pyridinyl‐9‐[4‐(4‐pyridinyl)phenyl]‐9H‐carbazole) and [Fe(PDPC)2(NCS)2] (2, PDPC = 3,6‐di(pyridin‐4‐yl)‐9‐phenyl‐9H‐carbazole). Analyses through single‐crystal X‐ray studies and magnetic measurements validate the two‐step SCO behavior of 1 within the temperature range of 50~200 K. Additionally, when combined with temperature‐dependent fluorescence emission spectroscopy, the results demonstrate the coexistence of SCO and fluorescence in 1.

Development of a high throughput oxidation profiling strategy for monoclonal antibody products

Oxidation is one of the most common degradation pathways of biopharmaceutics, potentially leading to altered product stability, pharmacokinetics, reduced biological activity and/or an increased immunogenicity. However, it is often insufficiently assessed in early development stages, leaving potential molecule liabilities undiscovered. Aim of the present work was the development of a high throughput oxidation profiling strategy, applicable throughout various stages of biopharmaceutical development. The study demonstrates that the combination of multiple stress assays, including peroxide-based, visible light, and metal-catalyzed oxidation (MCO), enables a comprehensive understanding of a mAb's oxidation susceptibility. The most effective parameters to evaluate oxidation in a high-throughput screening workflow are aggregation, tryptophan oxidation and changes in the hydrophobicity profile of the Fc and Fab subunit measured via Size Exclusion Chromatography, Intrinsic Tryptophan Fluorescence Emission spectroscopy and Reversed-Phase Chromatography subunit analysis, respectively. This oxidation profiling approach is valuable tool to systematically characterize the oxidation susceptibility under relevant conditions, time effective and with minimal sample consumption.

Poly(triphenylamine-thiazolo[5,4-d]thiazole) copolymer dyes with different anchoring end groups: Synthesis, dye-sensitized solar cell (DSSC) performance and femtosecond excited state absorption spectroscopy

In this study, the poly(triphenylaminethiazolo[5,4-d]thiazole) copolymer dyes having the different anchoring end groups of aldehyde (poly-TPATT-CHO; P5), sulfonic acid (poly-TPATT-SO3H; P5S) and cyanoacrylic acid (poly-TPATT-COOH; P5C) have been synthesized and used as sensitizers in dye-sensitized solar cells (DSSCs). The effects of the anchoring end groups of the P5, P5S and P5C copolymer dyes on the DSSC performance were examined. The synthesized copolymer dyes were characterized using 1H NMR, UV–vis. absorption and fluorescence (FL) emission spectroscopy, cyclic voltammetry (CV), MALDI-TOF-MS and FE-SEM-EDS methods. Among the studied polymers, the P5C polymer dye exhibited the best photovoltaic performance with a JSC of 6.46 mA cm−2, a VOC of 0.667 V, a FF of 0.70, and an overall power conversion efficiency (PCE) of 3.02 % under standard AM 1.5 G solar light conditions. These results are attributed to the strong binding ability of cyanoacrylic acid to the TiO2, leading to a greater photocurrent and hindered charge recombination. The effect of electron transfer mechanisms of the polymers on the DSSC performance have been investigated using the femtosecond transient absorption (fs TA) spectroscopy. The DSSC performance of the poly(triphenylaminethiazolo[5,4-d]thiazole) increased greatly by the presence of the cyanoacrylic acid anchoring end group in P5C polymer dye. The fs TA spectroscopy results revealed the presence of singlet–triplet transition for the P5C copolymer dye, while the P5 and P5S copolymers showed only singlet–singlet transitions. The observed triplet state transition in the P5C polymer increased the yield of the DSSC system.

Synthesis and Application of Specific N2H4 Fluorescent Probes with AIE Effect Based on Pyrazole Structure.

Two fluorescent probes, Y1-2 were synthesized from 2-acetonaphthone, 4-acetylbiphenyl, and phenyl hydrazine by Vilsmeier-Haack reaction and Knoevenagel condensation. Their recognition efficacies for N2H4 were tested by UV-visible absorption spectroscopy and fluorescence emission spectroscopy. The recognition mechanism were studies by density-functional theory calculations, and the effect of pH on N2H4 recognition was also studied. The results showed that the probe Y1-2 has high selectivity and a low detection limit for N2H4, and the recognition of N2H4 can be accomplished at physiological pH. The probes have had obvious aggregation-induced luminescence effect, large Stokes shift, high sensitivity, and can be successfully applied to live cell imaging.

Monitoring of DNA structural changes after incorporation of the phenylpyrazole insecticide fipronil

The use of insecticides presents a risk to the environment because they can accumulate in the water, soil, air, and organisms, endangering human and animal health. It is therefore essential to investigate the effects of different groups of insecticides on individual biomacromolecules such as DNA. We studied fipronil, which belongs to the group of phenylpyrazole insecticides. The interaction of fipronil with calf thymus DNA was investigated using spectroscopic methods (absorption and fluorescence spectroscopy) complemented with infrared spectroscopy and viscosity measurement. Fluorescence emission spectroscopy showed the formation of a fipronil/DNA complex with a combined static and dynamic type of quenching. The binding constant was 4.15 × 103 L/mol. Viscosity changes were recorded to confirm/disconfirm the intercalation mode of interaction. A slight change in DNA viscosity in the presence of fipronil was observed. The phenylpyrazole insecticide does not cause significant conformational changes in DNA structure or increase of its chain length. We hypothesize that fipronil is incorporated into the minor groove of the DNA macromolecule via hydrogen interactions as indicated by FT-IR and CD measurements.

Inactivation of polyphenol oxidase by low intensity DC field: Experiment and mechanism analysis via molecular dynamics simulation and molecular docking

In this study, inactivation of mushroom polyphenol oxidase (PPO) by low intensity direct current (DC) electric field and its molecular mechanism were investigated. In the experiments under 3 V/cm, 5 V/cm, 7 V/cm and 9 V/cm electric fields, PPOs were all completely inactivated after different exposure times. Under 1 V/cm, a residual activity of 11.88 % remained. The inactivation kinetics confirms to Weibull model. Under 1 ∼ 7 V/cm, n value closes to a constant about 1.3. The structural analysis of PPO under 3 V/cm and 5 V/cm by fluorescence emission spectroscopy and molecular dynamics (MD) simulation showed that the tertiary structure was slightly changed with increased radius of gyration, higher potential energy and rate of C-alpha fluctuation. After exposure to the electric field, most of the hydrophobic tryptophan (TRP) residues turned to the hydrophilic surface, resulting the fluorescence red-shifted and quenched. Molecular docking indicated that the receptor binding domain of catechol in PPO was changed. PPO under electric field was MD simulated the first time, revealing the changing mechanism of the electric field itself on PPO, a binuclear copper enzyme, which has a metallic center. All these suggest that the low intensity DC electric field would be a promising option for enzymatic browning inhibition or even enzyme activity inactivation.

Insights into the binding of buspirone to human serum albumin using multi-spectroscopic and molecular docking techniques

Buspirone is an anxiolytic drug that plays a significant role in managing anxiety disorders and alleviating their symptoms as well. Several techniques were utilized to study the interaction between buspirone and human serum albumin under physiological conditions, including UV-vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism, Fourier transform infrared spectroscopy (FT-IR), equilibrium dialysis, and molecular docking. The results of this study demonstrated that buspirone quenched the intrinsic fluorescence of human serum albumin through a mixed mechanism. Moreover, the binding constants (Kb), the quenching constants (Ksv), and thermodynamic parameters were calculated at various temperatures. The binding process of buspirone to human serum albumin showed a cooperative binding pattern, confirmed by the Scatchard diagram and Hill coefficient. Molecular docking results showed that buspirone interacted with the IIA, IIIA, and IIB subdomains of human serum albumin and slightly changed its conformation. It was also found that hydrophobic forces played a major role in this interaction. This study consequently proves that BSH as a drug can be transported by blood albumin. Additionally, due to its ratiometric response in absorbance upon binding to a biological target, HSA can be used as a molecular probe to follow biomolecular interactions.

Effects of ultraviolet radiation and reactive oxygen species on the structure and ligand-binding ability of human serum albumin for norfloxacin

To explore the influence of ultraviolet radiation (UV) and reactive oxygen species (ROS) on the structure and ligand-binding ability of human serum albumin (HSA) for norfloxacin (NFLX), HSA was treated with UV (HSAUV) and UV/H2O2 (HSAUV/H2O2), respectively. The structure difference of HSA, HSAUV and HSAUV/H2O2 were investigated by Fourier transform infrared, fluorescence (i.e., emission fluorescence, synchronous fluorescence and fluorescence lifetime) and circular dichroism spectroscopy. The intermolecular interactions of HSA, HSAUV and HSAUV/H2O2 with NFLX were studied at pH 7.4 and temperatures 291, 310, and 318 K, using fluorescence emission and synchronous fluorescence spectroscopy, and combined with molecular docking. The results suggested that UV and ROS could destroy the α-helix of HSA and induce the loose of HSA structure, and the average fluorescence lifetimes of HSA decreased from 6.12 ns to 3.76 ns (HSAUV) and 3.40 ns (HSAUV/H2O2). The conformational changes of HSA caused by UV and ROS allowed NFLX to get access to more potential binding sites and promoted the binding affinity of HSA for NFLX, while the temperature stability of the HSA-NFLX complex significantly decreased. The results are useful and valuable for evaluating the protein damage caused by UV and ROS in organisms.

Erbium(III) complexes with fluoroquinolones: Structure and biological properties

Four erbium(III) complexes with the fluoroquinolones enrofloxacin, levofloxacin, flumequine and sparfloxacin as ligands were synthesized and characterized by a wide range of physicochemical and spectroscopic techniques as well as single–crystal X–ray crystallography. The compounds were evaluated for their activity against the bacterial strains Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Xanthomonas campestris, which was higher than that of the corresponding free quinolones. The interaction mode of the complexes with calf–thymus DNA is via intercalation, as suggested by diverse studies such as UV–vis spectroscopy, DNA–viscosity measurements and competitive studies with ethidium bromide. Fluorescence emission spectroscopy revealed the high affinity of the complexes for bovine and human serum albumin and the determined binding constants suggested a tight and reversible binding of the compounds with both albumins.

Role of lignin in synergistic digestibility improvement of wheat straw by novel alkaline deep eutectic solvent and tetrahydrofuran pretreatment

A novel efficient pretreatment system containing alkaline deep eutectic solvent (DES) and tetrahydrofuran (THF) was developed in the present study. Under pretreatment conditions of 160 ℃ and 1 h, DES-THF pretreatment was more efficient (81.61%) in cellulose digestibility improvement than DES (choline chloride/monoethanolamine, 67.54%). To further explore lignin structural transformation and lignin-cellulase interaction after pretreatment, milled wood lignin (MWL) was extracted and characterized. Compared with DES-MWL, DES-THF-MWL showed an increased carboxyl group content (24.0%) and decreased condensed phenolic hydroxyl content (9.1%). In DES-MWL, β-O-4 content was 21.79%, while in DES-THF-MWL, β-O-4 accounted for 45.45%, indicating that the addition of THF alleviated cleavage of β-O-4 alkyl ether bonds. Fluorescence emission spectroscopy results showed that quenching mechanism of DES-THF-MWL and cellulase was dynamic, which was different from other lignin. Compared with DES-MWL, decreased Ka between DES-THF-MWL and cellulase indicated decreasing interaction between them. DES-THF pretreatment provides a novel pretreatment method for bioenergy.

Synthesis, Photophysical Properties and Self-Assembly of a Tetraphenylethylene-Naphthalene Diimide Donor-Acceptor Molecule.

The development of new π-conjugated molecular structures with controlled self-assembly and distinct photophysical properties is crucial for advancing applications in optoelectronics and biomaterials. This study introduces the synthesis and detailed self-assembly analysis of tetraphenylethylene (TPE) functionalized naphthalene diimide (NDI), a novel donor-acceptor molecular structure referred to as TPE-NDI. The investigation specifically focuses on elucidating the self-assembly behavior of TPE-NDI in mixed solvents of varying polarities, namely chloroform: methylcyclohexane (CHCl3 : MCH) and chloroform: methanol (CHCl3 : MeOH). Employing a several analytical methodologies, including UV-Vis absorption and fluorescence emission spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic light scattering (DLS), these self-assembled systems have been comprehensively examined. The results reveal that TPE-NDI manifests as distinct particles in CHCl3 : MCH (fMCH =90 %), while transitioning to flower-like assemblies in CHCl3 : MeOH (fMeOH =90 %). This finding underscores the critical role of solvent polarity in dictating the morphological characteristics of TPE-NDI self-assembled aggregates. Furthermore, the study proposes a molecular packing mechanism, based on SEM data, offering significant insights into the design and development of functional supramolecular systems. Such advancements in understanding the molecular self-assembly new π-conjugated molecular structures are anticipated to pave the way for novel applications in material science and nanotechnology.

Organofunctionalization of silica from rice husk ash with ESIPT dyes

Excited-state intramolecular proton transfer (ESIPT) dyes were immobilized on amorphous silica obtained from rice husk ash through surface modification methodology. The silanol groups present on the surface of silica were first functionalized with isocyanate groups to be reacted with ESIPT dyes. Scanning electron microscopy, infrared spectroscopy, thermogravimetric, nitrogen adsorption/desorption, powder X-ray diffraction, and solid-state fluorescence emission spectroscopy analysis have been carried out to characterize the materials. The synthesized silica-based fluorescent materials were used as latent fingerprint developer powders present on glass surfaces. The results showed that latent fingerprints were revealed with high contrast under ultraviolet light illumination.

Photocatalytic and antimicrobial studies of green synthesized Dy3+doped ZnO nanoparticles prepared from Rhododendron arboreum petal extract

In this study, the primary focus revolves around the synthesis of zinc oxide (ZnO) and dysprosium-doped zinc oxide (Dy-doped ZnO) nanoparticles utilizing a green chemistry approach, employing Rhododendron arboreum petal extract as a key component. A thorough characterization of nanoparticles has been carried out, involving a range of analytical techniques including UV–visible spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HRTEM), selected-area electron diffraction (SAED), and fluorescence emission spectroscopy. The structural examination confirmed the persistent hexagonal wurtzite structure of ZnO nanoparticles, which remained unaltered even with Dy doping. The XPS analysis corroborated the presence of lattice oxygen in addition to confirming the presence of Dy3+ and Zn2+. The results indicated that the incorporation of Dy3+ ions replaces Zn2+ ions in host ZnO leading to an increase in the defects inside ZnO. Based on HRTEM images, the particle size was determined to be 31 nm for ZnO nanoparticles and 39 nm for Dy-doped ZnO nanoparticles. FESEM imaging unveils a morphology reminiscent of pebbles, and EDX spectra provide additional evidence of the presence of Zn, Dy, and O elements within the nanoparticles, which aligns with the findings from XPS. Subsequently, these synthesized nanoparticles were harnessed for the remediation of novacron brown, a textile dye. Additionally, nanoparticles were explored for their antibacterial and antifungal properties which highlight the considerable potential of these nanoparticles in these specific domains.

Biodegradable Nanocomposite of ZnS(Mn) Quantum Dots Immobilized Graphene Oxide for Bioimaging Applications.

Developing a biocompatible and biodegradable graphene-based fluorescent nanoprobe with the ability to visualize live cells could be interesting for intracellular imaging and monitoring the efficiency of chemotherapy. Herein, we report a biodegradable and biocompatible hybrid fluorescent graphene oxide (GO)-ZnS(Mn) composite synthesized via in situ growth of ZnS(Mn) quantum dots (QDs) on the surface of GO in the aqueous medium. The prepared 'GO-ZnS(Mn)' composite was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and high-resolution transmission electron microscopy (HR-TEM) along with selected area electron diffraction (SAED). Further, the fluorescence properties of the GO-ZnS(Mn) composite were studied using fluorescence emission spectroscopy. The composite material exhibited a strong and broad visible light fluorescence from 500 to 600 nm by excitation with 365 nm (UV) light. The cytotoxic experiments of folic acid (FA) conjugated GO-ZnS(Mn) using MTT [(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)] assay revealed that the composite had excellent biocompatibility even at higher concentrations up to 200 µg/mL in HeLa cell lines. Next, the bioimaging experiments carried out using confocal fluorescence laser scanning microscopy (CLSM) revealed that GO-ZnS(Mn) composite was taken up by the HeLa cells effectively within 12 h of incubation via receptor (folate) mediated endocytosis with strong fluorescence throughout the cell surface. Finally, the biodegradability of GO-ZnS(Mn) composite was studied by treating it with human myeloperoxidase enzyme (hMPO) isolated from the primary immune cells, neutrophils, which is important to understand the in vivo fate of GO-Zns(Mn). The HR-TEM and Raman analyses confirmed the biodegradation of GO-ZnS(Mn) within 15 h of hMPO treatment. Thus, the biodegradable GO-ZnS (Mn) composite could be helpful for chemotherapy and bioimaging applications.

Effect of π-extension and halogenation on the optical limiting properties of meso-pyrenylBODIPYdyes

The lack of suitable optical limiters that cover the entire UV-visible-NIR region has motivated research to identify novel efficient and stable optical limiting materials. There has been a strong focus on attenuating the second harmonic of Nd:YAG pulsed lasers at 532 nm on the nanosecond timescale. The photophysicochemical processes of a series of mono- and di-(4-dimethylamino)styryl-meso-pyrenylBODIPY and mono- and di-(4-dimethylamino)buta-1,3-dienyl-meso-pyrenylBODIPY dyes were studied by UV-visible absorption and fluorescence emission spectroscopy, and by determining the fluorescence and triplet state lifetimes. Z-scan measurements were carried out at a fixed concentration of 10 [Formula: see text]M so that the effective nonlinear coefficients, third-order susceptibilities, second-order hyperpolarizabilities and limiting fluences of the dyes can be compared and trends in the structure-property relationships for these optical limiting parameters can be identified.

Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand.

Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(μ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(μ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(μ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(μ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1-C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV-Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1-C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo.

Mechanistic Insights into S-Depalmitolyse Activity of Cln5 Protein Linked to Neurodegeneration and Batten Disease: A QM/MM Study.

Ceroid lipofuscinosis neuronal protein 5 (Cln5) is encoded by the CLN5 gene. The genetic variants of this gene are associated with the CLN5 form of Batten disease. Recently, the first crystal structure of Cln5 was reported. Cln5 shows cysteine palmitoyl thioesterase S-depalmitoylation activity, which was explored via fluorescent emission spectroscopy utilizing the fluorescent probe DDP-5. In this work, the mechanism of the reaction between Cln5 and DDP-5 was studied computationally by applying a QM/MM methodology at the ωB97X-D/6-31G(d,p):AMBER level. The results of our study clearly demonstrate the critical role of the catalytic triad Cys280-His166-Glu183 in S-depalmitoylation activity. This is evidenced through a comparison of the pathways catalyzed by the Cys280-His166-Glu183 triad and those with only Cys280 involved. The computed reaction barriers are in agreement with the catalytic efficiency. The calculated Gibb's free-energy profile suggests that S-depalmitoylation is a rate-limiting step compared to the preceding S-palmitoylation, with barriers of 26.1 and 25.3 kcal/mol, respectively. The energetics were complemented by monitoring the fluctuations in the electron density distribution through NBO charges and bond strength alterations via local mode stretching force constants during the catalytic pathways. This comprehensive protocol led to a more holistic picture of the reaction mechanism at the atomic level. It forms the foundation for future studies on the effects of gene mutations on both the S-palmitoylation and S-depalmitoylation steps, providing valuable data for the further development of enzyme replacement therapy, which is currently the only FDA-approved therapy for childhood neurodegenerative diseases, including Batten disease.