Enantioselective separation and determination of ibuprofen: Stereoselective pharmacokinetics, pharmacodynamics and analytical methods.

Ibuprofen (IBP), the 29th most prescribed drug in the United States in 2019, is a widely used nonsteroidal anti-inflammatory drug (NSAID) comprising two enantiomers, (R)-IBP and (S)-IBP, collectively known as (RS)-IBP. This critical review examines analytical techniques for the enantioselective separation and determination of IBP enantiomers, crucial for pharmaceutical and clinical applications. The review focuses on state-of-the-art methods, including chromatographic techniques including high-performance liquid chromatography, gas chromatography, liquid chromatography-tandem mass spectrometry, and some other techniques. This review addresses pharmacokinetics, pharmacology, and side effects of each enantiomer, ensuring safe drug usage. By consolidating diverse analytical methods and their applicability in different matrices, this review serves as a valuable resource for researchers, analysts, and practitioners in pharmaceutical analysis, pharmacology, and clinical studies.

Stereoselective analysis of chiral pesticides: a review.

Chiral organic pollutants, including pesticides, herbicides, medicines, flame retardants, and polycyclic musk, represent a significant threat to both the environment and human health. The presence of asymmetric centers in the structure of chiral pesticides introduces stereoisomers with distinct distributions, fates, biomagnification capacities, and cytotoxicities. In aquatic environments, pesticides, as persistent/pseudo-persistent compounds, have been detected in substantial quantities, posing severe risks to non-target species and, ultimately, public health through water supply and food exposures. In response to this environmental challenge, stereoselective analytical methods have gained prominence for the identification of pesticide/drug enantiomers in recent years. This review examines the environmental impact of chiral pesticides, emphasizing the distinct biological activities and distribution patterns of their stereoisomers. By highlighting the advancements in liquid chromatography for enantiomeric analysis, the review aims to underscore the urgent need for a comprehensive understanding of these pollutants to facilitate informed remediation strategies and ensure the safer dispersal of chiral organic pollutants in the environment, thereby addressing the potential risks they pose to ecosystems and human health. Future research should focus on developing sustainable and efficient methodologies for the precise analysis of stereoisomers in complex matrices, particularly in sewage water, emphasizing the importance of sewage processing plants in ensuring water quality.

Effects of glucose and trehalose on tris-citric acid-egg yolk-fructose diluents for semen cryopreservation in goat.

Objectives: This study aimed to examine the impacts of the wide range of concentrations of glucose and trehalose on the tris-citric acid-egg yolk-fructose (TCEF) extenders for cryopreservation of goat semen. Materials and Methods: The sperm sample was pooled, washed, and diluted in control (TCEF without glucose and trehalose), TCEF + glucose (75, 150, 450, and 900 mm), and TCEF + trehalose (75, 150, 450, and 900 mm). After equilibrations, the semen straws were frozen under LN2 in the LN2 tank. After LN2 storage, the straws were thawed at 37°C for 30 seconds. The sperm parameters of all study groups were checked after equilibration and freezing. Results: After equilibration, the progressive motility (PM), total motility (TM), and viability of sperm in G-75, G-150, G-450, T-75, T-150, and T-450 were not significantly different (p < 0.05) from those in control. After cryopreservation and thawing, the PM, TM, and plasma membrane integrity (PMI) of T-150 were significantly higher (p < 0.05) than in control, G-75, G-900, T-75, and T-900. The viability of sperm in T-150 was substantially higher (p < 0.05) than in the control, whereas there was no significant difference among the control, G-75, G-900, T-75, and T-900. However, the acrosome integrity (AI) of sperm in G-900 was significantly decreased (p < 0.05) compared to the control, G-75, G-150, G-450, T-75, T-150, and T-450. Conclusion: According to the findings, the supplementation of 150 mm trehalose in the TCEF diluent was more efficient for sperm cryopreservation in the buck as reflected by PM, TM, viability, PMI, and AI.

Transition metal-based nanoparticles as potential antimicrobial agents: recent advancements, mechanistic, challenges, and future prospects.

Bacterial transmission is considered one of the potential risks for communicable diseases, requiring promising antibiotics. Traditional drugs possess a limited spectrum of effectiveness, and their frequent administration reduces effectiveness and develops resistivity. In such a situation, we are left with the option of developing novel antibiotics with higher efficiency. In this regard, nanoparticles (NPs) may play a pivotal role in managing such medical situations due to their distinct physiochemical characteristics and impressive biocompatibility. Metallic NPs are found to possess extraordinary antibacterial effects that are useful in vitro as well as in vivo as self-modified therapeutic agents. Due to their wide range of antibacterial efficacy, they have potential therapeutic applications via diverse antibacterial routes. NPs not only restrict the development of bacterial resistance, but they also broaden the scope of antibacterial action without binding the bacterial cell directly to a particular receptor with promising effectiveness against both Gram-positive and Gram-negative microbes. This review aimed at exploring the most relevant types of metal NPs employed as antimicrobial agents, particularly those based on Mn, Fe, Co, Cu, and Zn metals, and their antimicrobial mechanisms. Further, the challenges and future prospects of NPs in biological applications are also discussed.

Impact of Faradaic Interlayer Confinement and Carbon-Centered Macrostructure Designs for Ion Capture and the Recovery of Elements.

Environmental protection associated with renewable energy is among the most critical challenges for translational ion-capture based on capacitive storage of ions in electrical double layers at the interface of electrode and electrolyte. Electric double-layer capacitance with charge induction and faradaic pseudo-capacitance with charge transfer classifies the capacitance of the electrochemical interface. The electrochemical interface in most energy technologies involves porous and pseudocapacitive redox materials that offer varying degrees of electrolyte confinement. In this review, we discuss the factors affecting water desalination, such as the effect of nanopores for ion capture, the ion sieving effect, the effect of hydration energy, and hydration radius in the carbon sub-nanometer pore. Moreover, the surface phenomena of electrodes, including carbon corrosion, and the potential of zero charge to control the oxidation of carbon electrodes are explained along with protection mechanisms. The various capacitive deionization (CDI) operations and the corresponding electrochemical cell technologies are briefly introduced, including the significance of double-layer charging materials with faradaic intercalation, which suffer less from co-ion expulsion. Finally, we revisit the effects of various nanoarchitectures and the construction of capacitive deionization electrodes for clean water technology.

Free radical scavenging activity of gallic acid toward various reactive oxygen, nitrogen, and sulfur species: a DFT approach.

Gallic acid is a well-recognized naturally occurring compound possessing antioxidant activities. The free radical scavenging ability of gallic acid for fifty reactive species, such as oxygen, nitrogen, and sulfur-containing species, has been studied using the formal hydrogen atom transfer mechanism. The theoretical studies have been conducted in the gas phase and aqueous solution at M05-2X/6-311++G** level using the density functional theory (DFT) calculations. The relative damaging potential of all the reactive species has been compared by investigating their hydrogen atom and electron affinity. Furthermore, a comparison of their relative reactivity was made by evaluating several global chemical reactivity descriptors. Additionally, the feasibility of scavenging the species by gallic acid has been studied by computing the redox potentials and equilibrium constants for the overall process in the aqueous solution.

Recent advances in the antioxidant activity and mechanisms of chalcone derivatives: a computational review.

In this review, we have reported the antioxidant mechanisms and structure-antioxidant activity relationship of several chalcone derivatives, investigated in the recent past, based on the density functional theory (DFT) calculations, considering free radical scavenging and metal chelation ability. The antioxidant mechanisms include hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), single electron transfer followed by proton transfer (SET-PT), sequential proton loss hydrogen atom transfer (SPLHAT), sequential double proton loss electron transfer (SdPLET), sequential triple proton loss double electron transfer (StPLdET), sequential triple proton loss triple electron transfer (StPLtET), double HAT, double SPLET, double SET-PT, triple HAT, triple SET-PT, triple SPLET, proton-coupled electron transfer (PCET), single electron transfer (SET), radical adduct formation (RAF) and radical adduct formation followed by hydrogen atom abstraction (RAF-HAA). Furthermore, solvent effects have also been considered using different solvation models. The feasibility of scavenging different reactive oxygen and nitrogen species (ROS/RNS) has been discussed considering various factors such as the number and position of hydroxyl as well as methoxy groups present in the antioxidant molecule, stability of the species formed after scavenging reactive species, nature of substituent, steric effects, etc. This review opens new perspectives for designing new compounds with better antioxidant potential.

Molecular Insight into Dye-Surfactant Interaction at Premicellar Concentrations: A Combined Two-Photon Absorption and Molecular Dynamics Simulation Study.

Both electrostatic and hydrophobic interactions play pivotal roles in ligand-surfactant binding interaction, especially for ionic surfactants. While much studies have been reported in the micellar region, less attention has been paid on such interactions at a low (premicellar) surfactant concentration. We here study the interaction between the cationic dye rhodamine 6G (R6G) with surfactants of different charge types: anionic SDS, cationic CTAB, and nonionic Tx 100 using absorption and emission spectroscopy. We identify that R6G forms dimeric aggregates at a premicellar concentration of SDS. Formation of aggregates is also confirmed from classical simulation measurements. CTAB and Tx 100 do not form any such aggregate, presumably owing to unfavorable electrostatic interactions. For a molecular-level understanding, we perform two-photon absorption (TPA) spectroscopy for the same systems. TPA allows us to calculate the two-photon absorption cross section and subsequently the change in the dipole moment (Δµ) between ground and excited states of the dye. We calculate the Δµ and observe that it passes through a maximum at a surfactant concentration half of the critical micelle concentration of SDS. This observation imparts support to earlier quantum mechanical calculation, which infers deviation from the parallel orientation of the dye during surfactant-induced aggregation. We extended our measurements and varied the carbon chain length of the anionic surfactant, and we found that all of them exhibit a maximum in Δµ, while their relative magnitude is dependent on the surfactant carbon chain length.

Chirality of antidepressive drugs: an overview of stereoselectivity.

Stereochemistry plays an important role in drug design because the enantiomers of a drug frequently vary in their biological action and pharmacokinetic profiles. Racemates of a drug with either an inactive or an unsafe enantiomer can lead to detrimental effects. The manufacturing industry may still produce racemates, but such decisions must pass through rigorous analyses of the pharmacological and pharmacokinetic characteristics of the particular enantiomer related to the racemates. The pharmacokinetics of antidepressants or antidepressive agents is stereoselective and predominantly favors one enantiomer. The use of pure enantiomers offers (i) better specificity than the racemates in terms of certain pharmacological actions, (ii) enhanced clinical indications, and (iii) optimized pharmacokinetics. Therefore, controlling the stereoselectivity in the pharmacokinetics of antidepressive drugs is of critical importance in dealing with depression and psychiatric conditions. The objective of this review is to highlight the importance of the stereochemistry of antidepressants in the context of the design and development of new chirally pure pharmaceuticals, the potential complications caused by using racemates, and the benefits of using pure enantiomers.

Electrochemical detection of paracetamol and dopamine molecules using nano-particles of cobalt ferrite and manganese ferrite modified with graphite.

Some electrodes for efficient detection of paracetamol and dopamine were developed from nano sized material of cobalt ferrite (np-CoFe2O4) and manganese ferrite (np-MnFe2O4). These oxides were synthesized by combustion method using cobalt nitrate, manganese acetate and ferric nitrate as precursors in the presence of sugar and ethanolamine. The crystallite size, shape and morphology of nano material were characterized by X-ray diffraction pattern (XRD), field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDS) techniques. The crystallite sizes of synthesized nano-particles (nps) were in the range from 10 to 12 nm (calculated using Debye-Scherrer equation) with cubic crystal system. These particles were utilized as electrode modified with graphite for simultaneous detection of paracetamol and dopamine through cyclic voltammetry and Differential pulse voltammetry techniques and was found to be superior to reported literatures. The minimum detection limit of paracetamol and dopamine at CoFe2O4/GP electrode were 250 nM and 350 nM while at MnFe2O4/GP electrode it was 300 nM and 400 nM, respectively. Both the electrodes exhibited the linearity range from3 µM to 200 µM & 3 µM-160 µM for paracetamol and 3 µM-180 µM & 5 µM to 200 for dopamine, respectively. Two oxidation peaks of paracetamol and dopamine were well separated in phosphate buffer (pH = 6) in mixture with 100 mVs-1 and 50 mVs-1 scan rate for cyclic voltammetry and Differential pulse voltammetry, respectively. Both the electrodes demonstrated satisfactory results in real samples of paracetamol and dopamine.

Correction: Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial ischemic reperfusion injury.

Correction for 'Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial ischemic reperfusion injury' by Hannah Rachel Vasanthi et al., Food Funct., 2010, 1, 278-283.

Two Photon Spectroscopy Can Serve as a Marker of Protein Denaturation Pathway.

Rhodamine group of molecules are widely used dyes for imaging of biological molecules. Application of these dyes however includes a limitation that these molecules absorb in the visible range of the spectrum, which does not fall in the 'biologically transparent window' (BTW). Two photon absorption (TPA) process could come up with an alternate solution to this as these dyes could be excited in the near infrared (NIR) window to extract similar information. To validate this we have investigated TPA cross section (TPACS, σ2) of two rhodamine dyes, namely Rhodamine 6G (R6G), Rhodamine B (RhB), site selectively bound with a model protein, bovine serum albumin (BSA), by exciting at 800 nm. Two photon spectroscopy and imaging confirms the binding of the dye to the protein. The decreases in TPACS with increasing temperature at a fixed BSA concentration excellently follows the temperature induced structural transition of BSA as the protein transforms from a molten globule to unfolded conformation beyond 60 °C, which has previously been established through circular dichroism (CD) measurements. The thus established resemblance in TPACS and CD measurement trends thus strongly affirms the suitability of TPA process in protein imaging and as an alternative marker to tracking its conformational transformations using NIR radiation.

Modulation of the Excited-State Proton Transfer Rate of d-luciferin in Mixed Reverse Micellar Systems.

The excited-state proton transfer (ESPT) rate of photo-acids in a confined medium depends on several physical parameters of the immediate environment. We introduce a new parameter in the form of charge type at the interface of reverse micellar (RM) systems to modulate the ESPT rate. We investigate the ESPT reaction of d-luciferin in mixed RM systems composed of nonionic polyoxyethylene(5)nonylphenylether (Igepal CO-520) with cationic didodecyldimethylammonium bromide (DDAB) and anionic sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in cyclohexane (Cy) at different mole fractions of Ig (X Ig) and fixed hydration. ESPT is feeble in AOT RM, whereas it is favorable in the other two RMs. Addition of Ig is observed to facilitate ESPT in AOT RM linearly, whereas in DDAB, it shows a synergistic effect. The various physical parameters of water in the mixed RM water pool have been investigated using dynamic light scattering, Fourier transform infrared, and time-resolved fluorescence spectroscopy measurements to underline the ESPT mechanism in these mixed RMs.

Nonmonotonic Hydration Behavior of Bovine Serum Albumin in Alcohol/Water Binary Mixtures: A Terahertz Spectroscopic Investigation.

We report the experimental observation of nonmonotonic changes in the collective hydration of bovine serum albumin (BSA) in the presence of alcohols of varying carbon-chain lengths, that is, ethanol, 2-propanol, and tert-butyl alcohol (TBA), by using terahertz (THz) time domain spectroscopy. We measured the THz absorption coefficient (α) of the protein solutions, and it was observed that α fluctuated periodically as a function of alcohol concentration at a fixed protein concentration. For a fixed alcohol concentration, an increase in the protein concentration resulted in nonmonotonic changes in α; thus, it first decreased rapidly and then increased, which was followed by a shallow decrease. An alcohol-induced α helix to random coil transition of the protein secondary structure was revealed by circular dichroism spectroscopy measurements, and the effect was most prominent in TBA. The anomalous change in the hydration was found to be a delicate balance between the various interactions present in the three-component system.

Enhanced Catalytic Activity of α-Chymotrypsin in Cationic Surfactant Solutions: The Component Specificity Revisited.

Enhanced catalytic activity (super activity) of enzymes in the presence of surfactants is of key importance in "micellar enzymology"; such super activity is not very trivial, it is highly system specific, and the mechanism behind the activity enhancement is not always well apprehended. We report the catalytic activity of α-chymotrypsin (CHT) on ala-ala-phe-7-amido-4-methylcoumarin (AMC) in the presence of cationic surfactants of different hydrophobic chain lengths: dodecyltrimethylammonium bromide (DTAB), cetyltrimethylammonium bromide (CTAB) and octadecyltrimethylammonium bromide (OTAB). It is observed that in comparison to buffer the catalytic activity of CHT is enhanced 5-fold in premicellar DTAB solutions, while negligible changes are observed in CTAB and OTAB. Activity decreases considerably in the post micellar concentration, specifically for the latter two surfactants. A similar trend is also obtained in another substrate 2-napthyal acetate hydrolysis. Such surfactant specific superactivity is intriguing. The protein's secondary and tertiary structures in the presence of these surfactants are determined using circular dichroism (CD) spectroscopy and it is found that both CTAB and OTAB perturb the protein structure significantly, especially in the post micellar concentrations. DTAB, on the other hand, does not produce noticeable changes in the protein structure. The various pairwise interactions present in the system have been underlined using both steady-state and time-resolved fluorescence spectroscopy. Assuming a three-step kinetics model, we determine the free energy changes of the reaction, and the observations have been discussed in the light of the various interactions among the components.

An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles.

We have developed a strategy for targeted delivery of metal-diketo complex, "bis(2,4-pentanedionato) copper(II)" to breast cancer cells both in-vitro and in-vivo. This metal-organic complex induced ROS and subsequently DNA damage as well as mitochondrial membrane depolarization was observed. The mitochondria rupture further triggered apoptosis. For in-vitro targeting strategies, two different approaches were employed, folic acid or her-2 specific peptide (KCCYSL) was attached to stearic acid-modified polymeric Chitosan nanoparticles loaded with metal-organic complex "bis(2,4-pentanedionato)copper(II)". This was tested on two pairs of isogenic cells (FR+/FR- MCf-7 and her2+ /her2- MCF-7) and it was observed that cells expressing the receptor were susceptible to the drug whereas non-expressing isogenic cells were almost un-affected. During in-vivo studies, mice receiving targeted delivery of bis(2,4-pentanedionato) copper (II) had increased survivability and reduced tumor volume compared to non-targeted drug delivery. During toxicity studies for liver enzymes it was also found that the mice receiving targeted drug did not show any sign of liver damage as well as other histology changes.

Preferential solvation of lysozyme in dimethyl sulfoxide/water binary mixture probed by terahertz spectroscopy.

We report the changes in the hydration dynamics around a model protein hen egg white lysozyme (HEWL) in water-dimethyl sulfoxide (DMSO) binary mixture using THz time domain spectroscopy (TTDS) technique. DMSO molecules get preferentially solvated at the protein surface, as indicated by circular dichroism (CD) and Fourier transform infrared (FTIR) study in the mid-infrared region, resulting in a conformational change in the protein, which consequently modifies the associated hydration dynamics. As a control we also study the collective hydration dynamics of water-DMSO binary mixture and it is found that it follows a non-ideal behavior owing to the formation of DMSO-water clusters. It is observed that the cooperative dynamics of water at the protein surface does follow the DMSO-mediated conformational modulation of the protein.

Direct observation of coherent oscillations in solution due to microheterogeneous environment.

We report, for the first time, direct observation of coherent oscillations in the ground-state of IR775 dye due to microheterogeneous environment. Using ultrafast near-infrared degenerate pump-probe technique centered at 800 nm, we present the dynamics of IR775 in a binary mixture of methanol and chloroform at ultra-short time resolution of 30 fs. The dynamics of the dye in binary mixtures, in a time-scale of a few fs to ~740 ps, strongly varies as a function of solvent composition (volume fraction). Multi-oscillation behavior of the coherent vibration was observed, which increased with decreasing percentage of methanol in the dye mixture. Maximum number of damped oscillations were observed in 20% methanol. The observed vibrational wavepacket motion in the ground-state is periodic in nature. We needed two cosine functions to fit the coherent oscillation data as two different solvents were used. Dynamics of the dye molecule in binary mixtures can be explained by wavepacket motion in the ground potential energy surface. More is the confinement of the dye molecule in binary mixtures, more is the number of damped oscillations. The vibrational cooling time, τ2, increases with increase in the confinement of the system. The observed wavepacket oscillations in ground-state dynamics continued until 1.6 ps.

Control of femtosecond laser driven retro-Diels-Alder-like reaction of dicyclopentadiene.

Using femtosecond time resolved degenerate pump-probe mass spectrometry coupled with simple linearly chirped frequency modulated pulse, we elucidate that the dynamics of retro-Diels-Alder-like reaction of diclopentadiene (DCPD) to cyclopentadiene (CPD) in supersonic molecular beam occurs in ultrafast time scale. Negatively chirped pulse enhances the ion yield of CPD, as compared to positively chirped pulse. This indicates that by changing the frequency (chirp) of the laser pulse we can control the ion yield of a chemical reaction.

Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial ischemic reperfusion injury.

Hydroalcoholic extract of Dioscorea bulbifera (DB), a yam variety called air potato, was tested for its protective effect on myocardial ischemic/reperfusion (I/R) injury in rats due to apoptosis and necrosis. Myocardial I/R injury was induced by 30 min ischemia followed by 2 h reperfusion by perfusing isolated rat hearts with Krebs Henseilet bicarbonate (KHB) buffer in a Langendorff set up. Pretreatment of DB (150 mg kg(-1) body weight) for 30 days significantly reduced myocardial infarct size and improved the ventricular function (aortic flow and coronary flow, LVDP, LVmax dp/dt). Role of DB on apoptosis was also evaluated by determining caspase 3 as well as by examining pro-apoptotic and anti-apoptotic proteins Bax and Bcl2 by Western blot analysis followed by TUNEL assay. DB also prevented I/R-mediated down regulation of survival protein Akt and HO-1. Our results indicated that Dioscorea bulbifera could ameliorate myocardial ischemia and reperfusion injury by improving ventricular function and inhibition of cardiomyocyte necrosis and apoptosis.