Thermodynamic Study of 1,4-Bis(3-methylimidazolium-1-yl)butane Bis(trifluoromethylsulfonyl)imide ([C4(MIm)2][NTf2]2) from 6 to 350 K.

The molar heat capacity of 1,4-bis(3-methylimidazolium-1-yl)butane bis(trifluoromethylsulfonyl)imide dicationic ionic compound ([C4(MIm)2][NTf2]2) has been studied over the temperature range from 6 to 350 K by adiabatic calorimetry. In the above temperature interval, this compound has been found to form crystal, liquid, and supercooled liquid. For [C4(MIm)2][NTf2]2, the temperature of fusion T°fus = (337.88 ± 0.01) K has been determined by the fractional melting experiments, the enthalpy of fusion ΔfusH° = (52.79 ± 0.28) kJ mol-1 has been measured using the calorimetric method of continuous energy input, and the entropy of fusion ΔfusS° = (156.2 ± 1.7) J K-1 mol-1 has also been evaluated. The standard thermodynamic functions of the studied dicationic ionic compound, namely, the heat capacity Cp°(T), the enthalpy [H°(T) - H°(0)], the entropy S°(T) and the Gibbs free energy [G°(T) - H°(0)] have been calculated on the basis of the experimental data for the temperature range up to 350 K. The results have been discussed and compared with those available in the literature and in the NIST Ionic Liquids Database (ILThermo) for monocationic ionic compounds.

Cyclodextrin-assisted surface-enhanced Raman spectroscopy: a critical review.

Numerous approaches have been proposed to overcome the intrinsically low selectivity of surface-enhanced Raman spectroscopy (SERS), and the modification of SERS substrates with diverse recognition molecules is one of such approaches. In contrast to the use of antibodies, aptamers, and molecularly imprinted polymers, application of cyclodextrins (CDs) is still developing with less than 100 papers since 1993. Therefore, the main goal of this review is the critical analysis of all available papers on the use of CDs in SERS analysis, including physicochemical studies of CD complexation and the effect of CD presence on the Raman enhancement. The results of the review reveal that there is controversial information about CD efficiency and further experimental investigations have to be done in order to estimate the real potential of CDs in SERS-based analysis.

Thermodynamic Study of Formamidinium Lead Iodide (CH5N2PbI3) from 5 to 357 K.

In the present study, the molar heat capacity of solid formamidinium lead iodide (CH5N2PbI3) was measured over the temperature range from 5 to 357 K using a precise automated adiabatic calorimeter. In the above temperature interval, three distinct phase transitions were found in ranges from 49 to 56 K, from 110 to 178 K, and from 264 to 277 K. The standard thermodynamic functions of the studied perovskite, namely the heat capacity C°p(T), enthalpy [H0(T) - H0(0)], entropy S0(T), and [G°(T) - H°(0)]/T, were calculated for the temperature range from 0 to 345 K based on the experimental data. Herein, the results are discussed and compared with those available in the literature as measured by nonclassical methods.

Thermodynamic Properties of the First-Generation Hybrid Dendrimer with "Carbosilane Core/Phenylene Shell" Structure.

The molar heat capacity of the first-generation hybrid dendrimer with a "carbosilane core/phenylene shell" structure was measured for the first time in the temperature range T = 6-600 K using a precise adiabatic vacuum calorimeter and DSC. In the above temperature interval, the glass transition of the studied compound was observed, and its thermodynamic characteristics were determined. The standard thermodynamic functions (the enthalpy, the entropy, and the Gibbs energy) of the hybrid dendrimer were calculated over the range from T = 0 to 600 K using the experimentally determined heat capacity. The standard entropy of formation of the investigated dendrimer was evaluated at T = 298.15 K. The obtained thermodynamic properties of the studied hybrid dendrimer were compared and discussed with the literature data for some of the first-generation organosilicon and pyridylphenylene dendrimers.

Determination of methotrexate in spiked human urine using SERS-active sorbent.

This report is dedicated to determination of anticancer drug methotrexate (MTX) in human urine using surface-enhanced Raman spectroscopy (SERS). Aluminum oxide loaded with silver nanoparticles (AO-Ag) was proposed as SERS-active sorbent and used for solid-phase extraction (SPE) of the analyte and its SERS-based determination (SPE-SERS protocol). MTX has strong SERS signal only in alkaline media that challenges its determination in urine due to strong background signal caused by creatinine. The application of SPE step enables to purify and concentrate the analyte making MTX determination possible. Also, the application of the same material for SPE pretreatment and SERS analysis enables to simplify and speed-up the protocol. The protocol was developed and tested using artificially spiked samples of human urine collected during different time of day to account deviating composition of the urine matrix. The use of dilution step of the analyte-containing urine was proposed prior SPE-SERS protocol to reduce the difference between morning-time- and daytime-collected urine achieving maximal reliability of the analysis. Additional physicochemical study was performed to estimate an influence of the primary intrinsic urine components (salts, urea, creatinine) and their mixtures on the analytical signal. Final protocol enables MTX determination in human urine within 20-300 µg mL-1 range of concentrations with satisfactory precision (11-19% RSD), accuracy (97-104% apparent recovery), and limit of detection (4.2 µg mL-1). Accounting that the analysis requires less than 15 min and portable Raman spectrometer, the protocol seems to be promising for therapeutic drug monitoring in hospitals to identify poor MTX clearance in a timely manner and minimize adverse effects of therapy. Graphical Abstract.

Optical sensors for determination of biogenic amines in food.

This review presents the state-of-the-art of optical sensors for determination of biogenic amines (BAs) in food by publications covering about the last 10 years. Interest in the development of rapid and preferably on-site methods for quantification of BAs is based on their important role in implementation and regulation of various physiological processes. At the same time, BAs can develop in different kinds of food by fermentation processes or microbial activity or arise due to contamination, which induces toxicological risks and food poisoning and causes serious health issues. Therefore, various optical chemosensor systems have been devised that are easy to assemble and fast responding and low-cost analytical tools. If amenable to on-site analysis, they are an attractive alternative to existing instrumental analytical methods used for BA determination in food. Hence, also portable sensor systems or dipstick sensors are described based on various probes that typically enable signal readouts such as photometry, reflectometry, luminescence, surface-enhanced Raman spectroscopy, or ellipsometry. The quantification of BAs in real food samples and the design of the sensors are highlighted and the analytical figures of merit are compared. Future instrumental trends for BA sensing point to the use of cell phone-based fully automated optical evaluation and devices that could even comprise microfluidic micro total analysis systems.

Sample pretreatment and SERS-based detection of ceftriaxone in urine.

The aim of the work is the development of the procedure for ceftriaxone (antibiotic drug of cephalosporin class) detection in urine using surface-enhanced Raman spectroscopy (SERS). Hydroxylamine stabilized silver nanoparticles were used as SERS-active material. Additional urine pretreatment steps were developed in order to eliminate the influence of creatinine on the ceftriaxone SERS signal. These steps include adjusting of the sample pH to alkaline value (pH 13) and purification of the sample using silica gel column chromatography. Alkali pH increases SERS signal of ceftriaxone, while silica gel separates the analyte from creatinine-the main admixture in urine which provides inappropriate SERS signal background. Additionally, it was found that total protein content up to 0.2 mg/mL (upper level for urine of healthy person) and pH deviation of initial urine do not influence on SERS signal of ceftriaxone. The proposed detection procedure enables fast (~ 10 min) determination of ceftriaxone in artificially spiked urine samples within 5 to 500 µg/mL range of concentrations which matches the range of the drug concentrations in urine after injection of therapeutically required dosages. Limits of detection (3σ) and quantification (10σ) were found to be 0.4 and 2.0 µg/mL, correspondingly. Graphical abstract Application of urine pretreatment enables the purification of target analyte from intrinsic urine components and improves SERS-based detection of ceftriaxone (antibiotic drug).

SERS detection of ceftriaxone and sulfadimethoxine using copper nanoparticles temporally protected by porous calcium carbonate.

The authors describe a new composite based on SERS-active copper nanoparticles (CuNPs; 10 ± 2 nm) incorporated into calcium carbonate microspheres (CaCO3-CuNPs; 3.4 ± 0.3 µm). The CaCO3 coating acts as a temporal protector of CuNPs against oxidation. Incorporated CuNPs have significantly improved stability during storage and a month-long shelf lifetime. The composite was used for SERS detection of rhodamine 6G and two antibacterial drugs (ceftriaxone and sulfadimethoxine). Two analytical formats, one with and one without solid phase extraction, are introduced to demonstrate the flexibility of the method. Both formats imply the dissolution of CaCO3 matrix before SERS analysis to release CuNP used as SERS substrate. The study of the influence of pH value and acid nature on the SERS signal demonstrated that HCl is the most efficient candidate to release the CuNPs. Sensitivity (expressed as LOD) is shown to be improved by more than one order when solid phase extraction is used. The average SERS enhancement factor is 10^7 which makes the material efficiency comparable to the one of silver nanoparticles. The LOD (<5 µM), precision (RSDs between 20 and 24% at LOD levels), and trueness (apparent recoveries 84-113%) for the two antibiotics (ceftriaxone and sulfadimethoxine) make the method quite useful for quantitative analysis and therapeutic drug monitoring at physiologically relevant concentrations. Graphical abstract A composite with temporally stable copper nanoparticles was synthesized, studied, and used for SERS detection of two antibacterial drugs. The analytical efficiency of the composite was found appropriate for quantitative analysis due to Raman enhancement comparable with silver nanostructures.

Betulin-3,28-diphosphate. Physico-Chemical Properties and In Vitro Biological Activity Experiments.

Betulin-3,28-diphosphate (BDP) obtained by phosphorylation of betulin using POCl3 has two main structural forms-BDP-1 and BDP-2-which differ in ethanol solubility, melting point, FTIR spectra, thermoanalytical characteristics and biological activity. Betulin-3,28-diphosphate and its sodium salt (Na-BDP) were characterized using 13C and 31P-NMR spectra, powder XRD experiments, as well as differential scanning calorimetry (DSC) and thermogravimetric analysis (TG) methods. The exo-effects at 193 ± 8 °C for ethanol soluble BDP-1 samples (-19.7 ± 0.2 kJ∙mol-1) were about three times less than for ethanol insoluble BDP-2 samples f (-70.5 ± 0.7 kJ∙mol-1). The DSC curves of Na-BDP-1 and Na-BDP-2 characterized the endo-effects having a maximum at 95⁻112 °C. Water-soluble Na-BDP-1 was obtained as needle-like crystals, unlike poorly crystalline Na-BDP-2, whereas BDP-1 and BDP-2 aged with time and were isolated as amorphous substances. In vitro experiments on rats showed that compared to the control, Na-BDP-1 increased catalase and SOD activity and improved energy metabolism more effectively than Na-BDP-2.

Standard Thermodynamic Functions of Tripeptides N-Formyl-l-methionyl-l-leucyl-l-phenylalaninol and N-Formyl-l-methionyl-l-leucyl-l-phenylalanine Methyl Ester.

The heat capacities of tripeptides N-formyl-l-methionyl-l-leucyl-l-phenylalaninol (N-f-MLF-OH) and N-formyl-l-methionyl-l-leucyl-l-phenylalanine methyl ester (N-f-MLF-OMe) were measured by precision adiabatic vacuum calorimetry over the temperature range from T = (6 to 350) K. The tripeptides were stable over this temperature range, and no phase change, transformation, association, or thermal decomposition was observed. The standard thermodynamic functions: molar heat capacity Cp,m, enthalpy H(T) - H(0), entropy S(T), and Gibbs energy G(T) - H(0) of peptides were calculated over the range from T = (0 to 350) K. The low-temperature (T ≤ 50 K) heat capacities dependencies were analyzed using the Debye's and the multifractal theories. The standard entropies of formation of peptides at T = 298.15 K were calculated.

SERS as a tool for determination of structurally related compounds: The case of sulfanilamide class antibiotics.

Analysis of real objects based on surface-enhanced Raman spectroscopy (SERS) often utilizes new SERS substrates and/or complex analysis procedures, and they are optimized for only the determination of a single analyte. Moreover, analysis simplicity and selectivity are often sacrificed for maximum (sometimes unnecessary) sensitivity. Consequently, this trend limits the versatility of SERS analysis and complicates its practical implementation. Thus, we have developed a universal, but simple SERS assay suitable for the determination of structurally related antibiotics (five representatives of the sulfanilamide class) in complex objects (human urine and saliva). The assay involves only mixing of acidified analyzed solution with co-activating agent (polydiallyldimethylammonium chloride - PDDA) and SERS substrate (standard colloidal silver nanoparticles). Acidification promotes the generation of SERS spectra with maximum similarity and intensity, which is explained by the favorable enhancement of the protonated sulfanilamide moiety (a structurally similar part of the studied antibiotics) as a result of its strong electrostatic interaction with the SERS-active surface. Meanwhile, the addition of PDDA improves analysis selectivity by reducing background signal from body fluids, enabling to simplify sample pretreatment (dilution for urine; mucin removal and dilution for saliva). Therefore, the assay allows for rapid (≤10 min), precise, and accurate class-specific determination of sulfanilamides within concentration ranges suitable for non-invasive therapeutic drug monitoring in urine (40-600 µM) and saliva (10-30 µM). We also believe that thorough investigation of structurally related analytes and accompanying effects (e.g., high spectral similarity) is a promising direction to improve the understanding of SERS in general and expand its capabilities as an analytical tool.

New surface-enhanced Raman scattering platforms: composite calcium carbonate microspheres coated with astralen and silver nanoparticles.

Surface-enhanced Raman scattering (SERS) microspectroscopy is a very promising label-free, noncontact, and nondestructive method for real-time monitoring of extracellular matrix (ECM) development and cell integration in scaffolds for tissue engineering. Here, we prepare a new type of micrometer-sized SERS substrate, core-shell microparticles composed of solid carbonate core coated with silver nanoparticles and polyhedral multishell fullerene-like structure, astralen. Astralen has been assembled with polyallylamine hydrochloride (PAH) by the layer-by-layer manner followed by Ag nanoparticle formation by means of a silver mirror reaction, giving the final structure of composite particles CaCO3(PAH/astralen)x/Ag, where x = 1-3. The components of the microparticle carry multiple functionalities: (i) an easy identification by Raman imaging (photostable astralen) and (ii) SERS due to a rough surface of Ag nanoparticles. A combination of Ag and astralen nanoparticles provides an enhancement of astralen Raman signal by more than 1 order of magnitude. Raman signals of commonly used scaffold components such as polylactide and polyvinyl alcohol as well as ECM component (hyaluronic acid) are significantly enhanced. Thus, we demonstrate that new mechanically robust and easily detectable (by astralen signal or optically) core-shell microspheres based on biocompatible CaCO3 can be used as SERS platform. Particle design opens many future perspectives for fabrication of SERS platforms with multiple functions for biomedical applications, for example, for theranostic.

Cyclodextrin-assisted SERS determination of fluoroquinolone antibiotics in urine and blood plasma.

This paper describes the use of cyclodextrins (CDs) to improve the determination of fluoroquinolone antibiotics in human body fluids using surface-enhanced Raman spectroscopy (SERS). CDs were used to (i) prepare the CD-SERS substrate (synthesis and stabilization of silver nanoparticles), (ii) increase the sensitivity of the assay by enhancing the interaction between analyte molecules and the substrate, and (iii) improve the analysis accuracy by reducing the interaction between the substrate and endogenous components of body fluids. Two native CDs (α-CD and ß-CD) and two of their derivatives with hydroxypropyl groups were tested, and the best results were obtained with CD-SERS substrate prepared using native ß-CD. The CD-SERS assay has been developed and optimized for the determination of commonly used and structurally related fluoroquinolones (ciprofloxacin, norfloxacin, pefloxacin, and levofloxacin) in urine and blood plasma samples. Importantly, the non-significant difference in the interaction of the CD-modified SERS substrate with various fluoroquinolones has been successfully used to develop a versatile assay suitable for the analyte-class-specific analysis. Calibration plots were obtained for concentration ranges suitable for the determination of the antibiotics in urine (50-500 µg mL-1) and blood plasma (1-6 µg mL-1). The following figures of merit were obtained (for urine and blood plasma, respectively): RSD values are ≤15% and ≤23%, LOD values are 2.9-5.8 and 0.05-0.34 µg mL-1, recovery ranges are 96-105% and 91-111%. In addition, the influence of excessive concentrations of some main endogenous components of the body fluids on the analytical signal was studied. This step was used to evaluate possible limitations of the assay associated with the deviation of the composition of the body fluid matrix. Therefore, accounting for the short analysis time (≤15 min) and the use of a portable Raman spectrometer, the proposed assay can be suggested for therapeutic drug monitoring in hospitals.

Copper nanoparticles for SERS-based determination of some cephalosporin antibiotics in spiked human urine.

Copper nanoparticles (CuNPs) were prepared through a wet chemistry method to be used as substituents for noble-metal-based materials in the determination of cephalosporin antibiotics in urine using surface-enhanced Raman spectroscopy (SERS). The synthesis of the CuNPs was optimized to maximize the analytical signal, and microwave heating was used to increase the reaction rate and improve the homogeneity of the CuNPs. Ceftriaxone (CTR), cefazolin (CZL), and cefoperazone (CPR) were used as the analytes of interest. The determination tests were performed on artificially spiked samples of real human urine with concentrations corresponding to therapeutic drug monitoring (TDM) (50-500 µg mL-1). Urine samples collected in the morning and during the day were used to account for deviations in the urine composition, and the universality of the proposed protocol was ensured by performing sample dilution as a pretreatment. The use of calibration plots in the form of Freundlich adsorption isotherms yielded linear calibration plots. All limits of detection were lower than the minimal concentrations required for TDM, equaling 7.5 (CTR), 8.8 (CZL), and 36 (CPR) µg mL-1. Comparison of CuNPs with Ag and Au nanoparticles (AgNPs and AuNPs, respectively) confirmed that CuNPs offered a competitively high Raman enhancement efficiency (for excitation at 638 nm). Further, although the CuNPs demonstrated poorer temporal stability as compared with the AgNPs and AuNPs, the use of freshly prepared CuNPs resulted in satisfactory accuracy (recovery = 93-107%). Given the short analysis time (<20 min, including the time for the synthesis of the CuNPs and the SERS measurements using a portable Raman spectrometer), low sensitivity to the presence of the primary intrinsic urine components and satisfactory figures of merit of the proposed protocol for the determination of cephalosporin antibiotics in urine, it should be suitable for use in TDM.

Liquid-liquid extraction-assisted SERS-based determination of sulfamethoxazole in spiked human urine.

The determination of antibiotic levels in body fluids is of great importance in the field of personalized medicine and therapeutic drug monitoring. We report on the determination of sulfamethoxazole (SMX), an antibacterial drug of the sulfanilamide class, in spiked human urine. The protocol is based on the combination of surface-enhanced Raman spectroscopy (SERS) and liquid-liquid extraction (LLE-SERS analysis). First, the urine was diluted to reduce its buffer properties and the influence of the intrinsic urine components on the background SERS signal. Second, the acidification of the diluted urine and SMX extracts was performed to facilitate SMX extraction by chloroform and suppress the background signal, respectively. Finally, the SMX determination process was performed using hydroxylamine-stabilized silver nanoparticles as the SERS substrate. The efficiency and reliability of the LLE-SERS analysis were studied using spiked urine samples obtained from healthy volunteers with an SMX content within the therapeutically relevant concentration range (10-200 µg mL-1). Additionally, the verification of the analysis protocol was done using spiked urine samples obtained from oncology patients. The results of the verification demonstrate the applicability of the analysis for quantitative therapeutic drug monitoring due to the (i) strong suppression of the background SERS signal, which occurs as the result of LLE, dilution, and pH adjusting, (ii) satisfactory limit of detection of 1.7 µg mL-1, and (iii) simple, relatively fast (∼30 min), and cost-effective sample pretreatment.

Application of Aluminum Hydroxide for Improvement of Label-Free SERS Detection of Some Cephalosporin Antibiotics in Urine.

This report is dedicated to development of surface-enhanced Raman spectroscopy (SERS) based analysis protocol for detection of antibiotics in urine. The key step of the protocol is the pretreatment of urine before the detection to minimize background signal. The pretreatment includes extraction of intrinsic urine components using aluminum hydroxide gel (AHG) and further pH adjusting of the purified sample. The protocol was tested by detection of a single antibiotic in artificially spiked samples of real urine. Five antibiotics of cephalosporin class (cefazolin, cefoperazone, cefotaxime, ceftriaxone, and cefuroxime) were used for testing. SERS measurements were performed using a portable Raman spectrometer with 638 nm excitation wavelength and silver nanoparticles as SERS substrate. The calibration curves of four antibiotics (cefuroxime is the exception) cover the concentrations required for detection in patient's urine during therapy (25/100‒500 µg/mL). Random error of the analysis (RSD < 20%) and limits of quantification (20‒90 µg/mL) for these antibiotics demonstrate the applicability of the protocol for reliable quantitative detection during therapeutic drug monitoring. The detection of cefuroxime using the protocol is not sensitive enough, allowing only for qualitative detection. Additionally, time stability and batch-to-batch reproducibility of AHG were studied and negative influence of the pretreatment protocol and its limitations were estimated and discussed.

Low-temperature polymorphic phase transition in a crystalline tripeptide L-Ala-L-Pro-Gly·H2O revealed by adiabatic calorimetry.

We demonstrate application of precise adiabatic vacuum calorimetry to observation of phase transition in the tripeptide L-alanyl-L-prolyl-glycine monohydrate (APG) from 6 to 320 K and report the standard thermodynamic properties of the tripeptide in the entire range. Thus, the heat capacity of APG was measured by adiabatic vacuum calorimetry in the above temperature range. The tripeptide exhibits a reversible first-order solid-to-solid phase transition characterized by strong thermal hysteresis. We report the standard thermodynamic characteristics of this transition and show that differential scanning calorimetry can reliably characterize the observed phase transition with <5 mg of the sample. Additionally, the standard entropy of formation from the elemental substances and the standard entropy of hypothetical reaction of synthesis from the amino acids at 298.15 K were calculated for the studied tripeptide.

Thermodynamic Properties of Carbosilane Dendrimers of the Sixth Generation with Ethylene Oxide Terminal Groups.

The temperature dependences of heat capacities of carbosilane dendrimers of the sixth generation with ethyleneoxide terminal groups, denoted as G6[(OCH2CH2)1OCH3]256 and G6[(OCH2CH2)3OCH3]256, were measured in the temperature range from T = (6 to 520) K by precision adiabatic calorimetry and differential scanning calorimetry (DSC). In the above temperature range the physical transformations, such as glass transition and high-temperature relaxation transition, were detected. The standard thermodynamic characteristics of the revealed transformations were determined and analyzed. The standard thermodynamic functions, namely, heat capacity Cp°(T), enthalpy H°(T) - H°(0), entropy S°(T) - S°(0), and Gibbs energy G°(T) - H°(0) for the range from T → 0 to 520 K, and the standard entropies of formation ΔfS° of the investigated dendrimers in the devitrified state at T = 298.15 K, were calculated per corresponding moles of the notional structural units. The standard thermodynamic properties of dendrimers under study were discussed and compared with literature data for carbosilane dendrimers with different functional terminal groups.

Nanoencapsulated and microencapsulated SERS platforms for biomedical analysis.

The problems of layer-by-layer-based surface enhancement Raman scattering (SERS)-sensor application for pharmaceutical analysis were discussed. Layer-by-layer (LbL) method allows fabrication of encapsulated SERS platforms with high reproducibility of enhancement factor and increased signal/noise ratio of Raman scattering. LbL encapsulation approach opens an avenue to implement a novel type of theranostic systems combining SERS based sensing and drug delivery in one entity. The area of encapsulation development toward smart multifunctional theranostic systems could bring benefits for personalized medicine and should minimize costs and resources at preclinical and clinical study in pharmacology while testing new bioactive compounds.