Tannins Can Have Direct Interactions with Anthelmintics: Investigations by Isothermal Titration Calorimetry.

Plant tannins are known for their anthelmintic and antiparasitic activities and have been increasingly studied to battle the ever-growing problem of anthelmintic resistance. While tannins have been shown to exhibit these activities on their own, one approach would be to use them as complementary nutrients alongside commercial anthelmintics. So far, research on the interactions between tannins and anthelmintics is limited, and few studies have reported both synergistic and antagonistic effects depending on the type of tannin and the method used. These interactions could either strengthen or weaken the efficacy of commercial anthelmintics, especially if tannin-rich diets are combined with anthelmintics used as oral drenches. To study these interactions, a series of hydrolysable tannins (HTs) was selected, and their direct interactions with thiabendazole (TBZ) were evaluated by isothermal titration calorimetry (ITC), which allowed the detection of the exothermic interaction but also the roles and significances of different structural features of HTs in these interactions. Our results show that HTs can have a direct interaction with the benzimidazole anthelmintic TBZ and that the interaction is strengthened by increasing the number of free galloyl groups and the overall molecular flexibility of HTs.

Complementary Experimental Methods to Obtain Thermodynamic Parameters of Protein Ligand Systems.

In recent years, thermophoresis has emerged as a promising tool for quantifying biomolecular interactions. The underlying microscopic physical effect is still not understood, but often attributed to changes in the hydration layer once the binding occurs. To gain deeper insight, we investigate whether non-equilibrium coefficients can be related to equilibrium properties. Therefore, we compare thermophoretic data measured by thermal diffusion forced Rayleigh scattering (TDFRS) (which is a non-equilibrium process) with thermodynamic data obtained by isothermal titration calorimetry (ITC) (which is an equilibrium process). As a reference system, we studied the chelation reaction between ethylenediaminetetraacetic acid (EDTA) and calcium chloride (CaCl2) to relate the thermophoretic behavior quantified by the Soret coefficient ST to the Gibb's free energy ΔG determined in the ITC experiment using an expression proposed by Eastman. Finally, we have studied the binding of the protein Bovine Carbonic Anhydrase I (BCA I) to two different benzenesulfonamide derivatives: 4-fluorobenzenesulfonamide (4FBS) and pentafluorobenzenesulfonamide (PFBS). For all three systems, we find that the Gibb's free energies calculated from ST agree with ΔG from the ITC experiment. In addition, we also investigate the influence of fluorescent labeling, which allows measurements in a thermophoretic microfluidic cell. Re-examination of the fluorescently labeled system using ITC showed a strong influence of the dye on the binding behavior.

A spectrum-effect based method for screening antibacterial constituents in Niuhuang Shangqing Pill using comprehensive two-dimensional liquid chromatography.

To investigate and screen the active antibacterial constituents of Niuhuang Shangqing Pill (NSP), the current study developed a two-dimensional liquid chromatography (2DLC) method combining microcalorimetry technique. 60% ethanol extracts from 10 batches of different commercial NSP samples were analyzed and their chemical fingerprint were developed by the comprehensive 2DLC system of Shimadzu Nexera X2. Anti-streptococcus pneumoniae (SP) constituents were determined by microcalorimetry. Thermal kinetic parameters of the SP thermogram affected by 60% ethanol extracts from 10 NSP samples were analyzed by principal component analysis. Spectrum-effect correlation between comprehensive 2DLC fingerprint and the antibacterial activity were analyzed by orthogonal partial least squares (OPLS) and orthogonal partial least squares discriminant analysis (OPLS-DA). Findings showed that peak X1 (unknown), X9 (aloe-emodin), X10 (baicalein), X11 (unknown), X14 (wogonin), X15 (glycyrrhizic acid) and X17 (unknown) are the relevant components that are in positive correlation with inhibitory rate. Regarding inhibitory rate, X17 is the most powerful one, followed by X14, X15, X10, X11, X1 and X9, suggesting that compound X17, wogonin, glycyrrhizic acid and baicalein are the major active antibacterial components of NSP. The current method employing 2DLC with microcalorimetry technique proposes a new insight for screening and identifying antibacterial components in complex herbal formula.

Avaliação do desempenho de oleogéis estruturados com ceras vegetais como base lipídica reduzida em ácidos graxos saturados aplicados em cream cheeses / Performance evaluation of structured oleogels with vegetable waxes as a reduced lipid base in saturated fatty acids applied in cream cheeses

Diante das exigências crescentes das agências regulatórias do mundo todo quanto à redução/eliminação de ácidos graxos trans nos alimentos industrializados, bem como da conscientização do consumidor sobre a relação entre alimentação e saúde, o desenvolvimento de alternativas mais saudáveis aos óleos parcialmente hidrogenados e a outras fontes lipídicas com alto grau de saturaçã o se faz necessário. O oleogel, um sistema composto por um óleo preso em uma rede tridimensional formada por um agente estruturante, se apresenta como uma solução promissora. Dentre os diversos agentes estruturantes, as ceras vegetais se destacam por sua excelente capacidade de gelificação de óleos. Contudo, apresentam uma desvantagem sob o aspecto sensorial, pois podem conferir cerosidade e sabor residual desagradável aos alimentos. Com o objetivo de viabilizar o uso das ceras como agentes estruturantes em oleogéis face ao seu excelente desempenho tecnológico, este projeto propõe o estudo e a aplicação de oleogéis à base de óleo de soja (SBO) estruturado com ceras de farelo de arroz (RBW) a 2 e 4 % (m/m) ou carnaúba (CBW) a 3 e 6% (m/m), isoladamente. As matérias-primas foram caracterizadas e o comportamento de gelificação de cada cera foi avaliado por análises de textura por penetração de cone, estabilidade à perda de óleo por centrifugação, energia coesiva por parâmetro de solubilidade de Hansen (HSP) e comportamento de cristalização e fusão por calorimetria exploratória diferencial (DSC). Os resultados mostraram que ambas as ceras são capazes de formar oleogéis estruturalmente estáveis, contudo, o oleogel com 2% de RBW apresentou maior firmeza a 20 °C (190,4 gf/cm2) do que o oleogel com 6% de CBW a 5 °C (186,1 gf/cm2). Ao final de 5 dias, a capacidade de retenção de óleo do oleogel preparado com RBW foi de 100% às concentrações de 2 e 4% (m/m), contra 61 e 99,3% do oleogel elaborado com CBW às concentrações de 3 e 6% (m/m), respectivamente. Esses resultados podem ser explicados pela diferença entre as energias coesivas, ou seja, do grau de interação molecular entre o solvente e o soluto de cada oleogel. De acordo com os resultados de distância, que prevê se o gel formado será forte, fraco ou se não haverá formação de gel, o soluto CBW apresentou menor interação com o óleo (3,3 MPa1/2) do que o soluto RBW (3,7 MPa1/2). Os oleogéis foram aplicados como ingredientes em diferentes formulações de cream cheese, que foram analisados quanto a diferentes parâmetros de textura e esses resultados foram comparados a uma referência comercial. Nenhuma das amostras produzidas obteve resultados de textura estatisticamente iguais aos do cream cheese comercial (CC), o que pode ser explicado pelas diferenças de formulação e processamento dos produtos. Face aos resultados para textura e estabilidade à perda de óleo dos oleogéis de RBW, este agente estruturante apresenta ria maior potencial de aplicação, porém o oleogel CBW6 obteve alta capacidade de retenção de óleo (99,3%) e quando aplicado na formulação de cream cheese (CCBW6) apresentou resultados de firmeza e espalhabilidade mais próximos da amostra de referência, feita com gordura do leite (CMF)

Given the growing demands of regulatory agencies around the world regarding the reduction/elimination of trans fatty acids in processed foods, as well as consumer awareness about the relationship between food and health, the development of healthier alternatives to partially hydrogenated oils and others lipid sources with a high degree of saturation are necessary. Oleogel, a system composed of an oil trapped in a three-dimensional network formed by a structuring agent, presents itself as a promising solution. Among the various structuring agents, vegetable waxes stand out for their excellent oil gelling capacity. However, they have a sensory disadvantage, as they can give waxy and unpleasant aftertaste to foods. Aiming at enabling the use of waxes as structuring agents in oleogels in view of their excellent technological performance, this study proposes the evaluation and application of oleogels based on soybean oil (SBO) structured with rice bran wax (RBW) at 2 and 4% (m/m) or carnauba (CBW) at 3 and 6% (m/m). The raw materials were characterized and the gelling behavior of each wax was evaluated by analysis of texture by cone penetration, stability to oil loss by centrifugation, cohesive energy by Hansen solubility parameter (HSP) and crystallization and melting behavior. by differential scanning calorimetry (DSC). The results showed that both waxes are able to form structurally stable oleogels, however, oleogel with 2% RBW showed greater firmness at 20 °C (190.4 gf/cm2) than oleogel with 6% CBW at 5° C (186.1 gf/cm2). At the end of 5 days, the oil retention capacity of oleogel prepared with RBW was 100% at concentrations of 2 and 4% (m/m), against 61 and 99.3% of oleogel prepared with CBW at concentrations of 3 and 6% (m/m), respectively. These results can be explained by the difference between the cohesive energies, that is, the degree of molecular interaction between the solvent and the solute of each oleogel. According to the distance results, which predicts if the formed gel will be strong, weak or if there will be no gel formation, the CBW solute showed less interaction with the oil (3.3 MPa1/2) than the RBW solute (3 ,7 MPa1/2). Oleogels were applied as ingredients in different cream cheese formulations, which were analyzed for different texture parameters and these results were compared to a commercial reference. None of the samples produced had texture results statistically equal to those of commercial cream cheese (CC), which can be explained by the differences in formulation and processing of the products. Given the results for texture and oil binding capacity of RBW oleogels, this structuring agent would present greater application potential, but CBW6 oleogel obtained high oil biding capacity (99.3%) and when applied in cream cheese formulation (CCBW6) showed firmness and spreadability results closer to the reference sample, made with milk fat (CMF)

In Vitro Drug Efficacy Testing Against Trypanosoma brucei.

The recent endorsement of fexinidazole by the European Medicines Agency for the treatment of human African trypanosomiasis has demonstrated the high predictive value of cell-based assays for parasite chemotherapy. Here we describe three in vitro drug susceptibility tests with Trypanosoma brucei that have served as the basis for the identification of fexinidazole as a promising lead: (1) a standard assay with end-point measurement to determine drug efficacy; (2) a wash-out assay to test for reversibility and speed of drug action; (3) isothermal microcalorimetry for real-time measurement of onset of drug action and time to kill. Together, these assays allow to estimate pharmacodynamic parameters in vitro and to devise appropriate treatment regimens for subsequent in vivo experiments.

Aqueous solubility of beryllium(II) at physiological pH: effects of buffer composition and counterions.

Beryllium ion elicits p53-mediated cell cycle arrest in some types of human cancer cells, and it is a potent inhibitor of GSK3 kinase activity. Paradoxically, Be2+ is regarded to have almost negligible aqueous solubility at physiological pH, due to precipitation as Be(OH)2. This study demonstrates that the interaction of Be2+ with serum proteins greatly increases its effective solubility. In typical serum-supplemented mammalian cell culture medium, Be2+ was soluble up to about 0.5 mM, which greatly exceeds the concentration needed for biological activity. Some biochemical studies require protein-free Be2+ solutions. In such cases, the inclusion of a specific inorganic counterion, sulfate, increased solubility considerably. The role of sulfate as a solubility-enhancing factor became evident during preparation of buffered solutions, as the apparent solubility of Be2+ depended on whether H2SO4 or a different strong acid was used for pH adjustment. The binding behavior of Be2+ observed via isothermal titration calorimetry was affected by the inclusion of sodium sulfate. The data reflect a "Diverse Ion Effect" consistent with ion pair formation between solvated Be2+ and sulfate. These insights into the solubility behavior of Be2+ at physiological and near-physiological pH will provide guidance to assist sample preparation for biochemical studies.

A robust bacterial assay for high-throughput screening of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.

Hereditary tyrosinemia type 1 (HT1) and alkaptonuria (AKU) are inherited metabolic disorders caused by defective enzymes involved in tyrosine catabolism. Nitisinone, an ex-herbicide and member of the ß-triketone family, is therapeutically applied to prevent accumulation of toxic metabolites in patients by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD). Here, we developed a colorimetric bacterial whole-cell screening system that allows quantifying the inhibitory effects of human HPD inhibitors in a high-throughput and a robust fashion. The principle of our screening system is based on the degradation of tyrosine through 4-hydroxyphenylpyruvate into homogentisate by human HPD expressed in E. coli and subsequent production of a soluble melanin-like pigment. With the aim to optimise the assay, we tested different E. coli strains, expression and reaction temperatures, and time-points for supplementing the substrate. We found that in our assay the addition of prototypical ß-triketone HPD inhibitors decreases pigment production in a dose-dependent manner with increasing inhibitor concentrations. In addition, plate uniformity, signal variability and spatial uniformity assessment showed that we have developed a robust high-throughput screening assay that is simple to use, cost-effective and enables identification and evaluation of novel therapeutic human HPD inhibitors for the treatment of tyrosine-related metabolic disorders.

Hit-to-Lead: Hit Validation and Assessment.

High-throughput screening assays have become nearly ubiquitous in the search for small compounds or peptides that can modulate biological processes for therapeutic purposes. While many assays have become quite robust, with well-established protocols, the subsequent steps of validating the hits and choosing the best ones to take forward into leads for further chemical development are less established. In this chapter, we describe a variety of approaches, including chemical assessment, the use of various computational approaches, a variety of counter-screens, and "orthogonal" biophysical assays using nuclear magnetic resonance, surface plasmon resonance, isothermal titration calorimetry or thermal shift assays as methods for validating and assessing the quality of hits.

Sulfonamido-2-arylbenzoxazole GroEL/ES Inhibitors as Potent Antibacterials against Methicillin-Resistant Staphylococcus aureus (MRSA).

Extending from a study we recently published examining the antitrypanosomal effects of a series of GroEL/ES inhibitors based on a pseudosymmetrical bis-sulfonamido-2-phenylbenzoxazole scaffold, here, we report the antibiotic effects of asymmetric analogs of this scaffold against a panel of bacteria known as the ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). While GroEL/ES inhibitors were largely ineffective against K. pneumoniae, A. baumannii, P. aeruginosa, and E. cloacae (Gram-negative bacteria), many analogs were potent inhibitors of E. faecium and S. aureus proliferation (Gram-positive bacteria, EC50 values of the most potent analogs were in the 1-2 µM range). Furthermore, even though some compounds inhibit human HSP60/10 biochemical functions in vitro (IC50 values in the 1-10 µM range), many of these exhibited moderate to low cytotoxicity to human liver and kidney cells (CC50 values > 20 µM).

Complete Kinetic Characterization of Enzyme Inhibition in a Single Isothermal Titration Calorimetric Experiment.

Techniques for rapidly measuring both the strength and mode of enzyme inhibitors are crucial to lead generation and optimization in drug development. Isothermal titration calorimetry (ITC) is emerging as a powerful tool for measuring enzyme kinetics with distinct advantages over traditional techniques. ITC measures heat flow, a feature of nearly all chemical reactions, and gives an instantaneous readout of enzyme velocity, eliminating the need for artificial substrates or postreaction processing. In principle, ITC is an ideal method for characterizing enzyme inhibition. However, existing ITC experiments are not well-suited to rapid throughput and few studies to date have employed this approach. We have developed a new ITC experiment, in which substrate and inhibitor are premixed in the injection syringe, that yields complete kinetic characterization of an enzyme inhibitor in an hour or less. This corresponds to savings in time and material of 5-fold or greater compared to previous ITC methods. We validated the approach using the trypsin inhibitor benzamidine as a model system, recapitulating both its competitive inhibition mode and binding constant. Our approach combines the rapid throughput of optimized spectroscopic assays with the universality and precision of ITC-based methods, providing substantially improved inhibitor characterization for biochemistry and drug development applications.

Cashew gum and maltrodextrin particles for green tea (Camellia sinensis var Assamica) extract encapsulation.

Cashew gum and maltodextrin microcapsules containing green tea leaf extracts were made using a spray-dryer. Green tea extracts were submitted to cytotoxicity analysis and characterization of bioactive compounds. Three formulations of microcapsules were performed, which were then submitted to characterization through morphological study, particle diameter and distribution, zeta potential, Exploratory Differential Calorimetry, entrapment efficiency, dissolution test and X-ray diffraction. The extract had a high bioactive compound content and no cytotoxicity was observed. The amorphous microcapsules presented irregular shapes with a circular predominance and dentate surface, mean diameters varying from 2.50 to 3.64 µm, solubility ranging from 63% to 72.66%. Low values of microencapsulation efficiency, zeta potencial and dissolution profile were observed. The microparticles based on the dry extract of green tea present potential as a food ingredient and as a promoter of health benefits.

Evaluation of butyrylcholinesterase inhibitory activity by chlorogenic acids and coffee extracts assed in ITC and docking simulation models.

In patients with Alzheimer's disease (AD), elevated levels of butyrylcholinesterase (BChE) are observed. The enzyme hydrolyses acetylcholine, which shows deficiency in these patients. Therefore, BChE inhibitors are used in the treatment of Alzheimer's disease, especially synthetic ones, showing side effects with long-term intake. The sources of natural BChE inhibitors are constantly being sought. Coffee brews have been shown to reduce the symptoms of AD in epidemiological studies. However, the ability to inhibit BChE activity has not been investigated, depending on the degree of coffee roasting. The study was aimed at determining the interactions between BChE and the bioactive compounds of coffee and their ability to inhibit the activity of BChE. A comparison of individual bioactive compounds of coffee as well as extracts obtained from two main species, Arabica and Robusta, and additionally from different degrees of roasting was made. Two models were used: isothermal titration calorimetry (ITC) and molecular docking simulation. ITC analysis showed strong interactions of ferulic and dihydrocaffeic acids with BChE. These compounds are the metabolites of the chlorogenic acids, including both mono- and diesters of caffeic acid with quinic acid. Docking simulation showed their strong hydrophobic interaction with BChE, stabilized by hydrogen bonds and pi-pi interactions. After introducing acetylcholine into the model system, the strongest ability to inhibit hydrolytic activity of BChE was again observed for ferulic acid and additionally for 3-caffeoylquinic acid, and among coffee brews the most active were light roasted Arabica and green Robusta. The study was based on the physiological concentrations of coffee components, so the potential therapeutic effect of coffee infusions was proved.

Zinc Bioavailability from Phytate-Rich Foods and Zinc Supplements. Modeling the Effects of Food Components with Oxygen, Nitrogen, and Sulfur Donor Ligands.

Aqueous solubility of zinc phytate (Ksp = (2.6 ± 0.2) × 10-47 mol7/L7), essential for zinc bioavailability from plant foods, was found to decrease with increasing temperature corresponding to ΔHdis of -301 ± 22 kJ/mol and ΔSdis of -1901 ± 72 J/(mol K). Binding of zinc to phytate was found to be exothermic for the stronger binding site and endothermic for the weaker binding site. The solubility of the slightly soluble zinc citrate and insoluble zinc phytate was found to be considerably enhanced by the food components with oxygen donor, nitrogen donor, and sulfur donor ligands. The driving force for the enhanced solubility is mainly due to the complex formation between zinc and the investigated food components rather than ligand exchange and ternary complex formation as revealed by quantum mechanical calculations and isothermal titration calorimetry. Histidine and citrate are promising ligands for improving zinc absorption from phytate-rich foods.

Origin and Formation Mechanism Investigation of Compound Precipitation from the Traditional Chinese Prescription Huang-Lian-Jie-Du-Tang by Isothermal Titration Calorimetry.

Previous studies have shown that compounds in the form of precipitate (CFP) from Huang-Lian-Jie-Du-Tang (HLJDT) were stable, and the CFP content reached 2.63% of the whole decoction and had good neuroprotective effects. However, there has been no research on their specific source. In this study, it was found that HLJDT CFP mainly came from the reaction of Scutellaria baicalensis and Coptis chinensis by studying the separated prescription components (accounting for 81.33% of HLJDT CFP). Unlike previous studies on HLJDT CFP, in this research the chemical composition of Scutellaria baicalensis-Coptis chinensis (SB-CC) CFP was identified by high performance liquid chromatography coupled with mass spectrometry (HPLC-MSn), which further proved that the main source of HLJDT CFP was Scutellaria baicalensis-Coptis chinensis CFP compared with previous HLJDT CFP studies. To explain the reaction mechanism between the decoctions of Scutellaria baicalensis and Coptis chinensis, isothermal titration calorimetry (ITC) was used to analyze their binding heat and the thermodynamic parameters (ΔH, ΔS, ΔG, n, Ka) of the reaction between baicalin and berberine, which are the main components of Scutellaria baicalensis and Coptis chinensis, respectively. The results showed that the reaction between decoctions of Scutellaria baicalensis and Coptis chinensis was exothermic and the reaction between baicalin and berberine was a spontaneous and enthalpy-driven chemical reaction, the binding ratio being 1:1. In addition, HLJDT CFP (EC50 = 14.71 ± 0.91 µg/mL) and SB-CC CFP (EC50 = 6.11 ± 0.12 µg/mL) showed similar protective activities on PC12 cells injured by cobalt chloride (CoCl2). This study provided a new angle to research on the main chemical components and therapeutic values of CFP in Traditional Chinese Medicine compounds.

Direct technique for monitoring lipid oxidation in water-in-oil emulsions based on micro-calorimetry.

An experimental device based on the measurement of the heat flux dissipated during chemical reactions, previously validated for monitoring lipid oxidation in plant oils, was extended to follow lipid oxidation in water-in-oil emulsions. Firstly, validation of the approach was performed by correlating conjugated diene concentrations measured by spectrophotometry and the heat flux dissipated by oxidation reactions and measured directly in water-in-oil emulsions, in isothermal conditions at 60°C. Secondly, several emulsions based on plant oils differing in their n-3 fatty acid content were compared. The oxidability parameter derived from the enthalpy curves reflected the α-linolenic acid proportion in the oils. On the whole, the micro-calorimetry technique provides a sensitive method to assess lipid oxidation in water-in-oil emulsions without requiring any phase extraction.

Interval Walking Training Can Increase Physical Fitness in Middle-Aged and Older People.

No long-term exercise training regimen with high adherence and effectiveness for middle-aged and older individuals is currently broadly available in the field. To address this problem, we developed an exercise training system comprising interval walking training and an information technology network that requires only minimal staff support. We hypothesized that our training system could increase physical fitness in older people.

Biophysics in drug discovery: impact, challenges and opportunities.

Over the past 25 years, biophysical technologies such as X-ray crystallography, nuclear magnetic resonance spectroscopy, surface plasmon resonance spectroscopy and isothermal titration calorimetry have become key components of drug discovery platforms in many pharmaceutical companies and academic laboratories. There have been great improvements in the speed, sensitivity and range of possible measurements, providing high-resolution mechanistic, kinetic, thermodynamic and structural information on compound-target interactions. This Review provides a framework to understand this evolution by describing the key biophysical methods, the information they can provide and the ways in which they can be applied at different stages of the drug discovery process. We also discuss the challenges for current technologies and future opportunities to use biophysical methods to solve drug discovery problems.

Solid-state characterization of optically pure (+)Dihydromyricetin extracted from Ampelopsis grossedentata leaves.

Dihydromyricetin (DMY) is a natural flavanol compound isolated from a traditional Chinese medicine, Ampelopsis grossedentata. Despite that optically pure (+)DMY is desired for treating chronic pharyngitis and alcohol use disorders, only DMY racemate is commercially available due to prolonged exposure time to high temperature and the presence of metal ions during industrial extraction, which cause racemization of the homochiral (+)DMY. We have developed an extraction method for successfully obtain optically pure (+)DMY. We have further assessed the physicochemical properties of the two phases using PXRD, DSC, TGA, FTIR, and moisture sorption. Among them, PXRD and FT-IR are suitable for quickly distinguishing homochiral (+)DMY from racemic (±)DMY. Lastly, with the aid of cocrystallization with theophylline, the absolute configuration of homochiral (+)DMY was identified to be (2R, 3R).

Structure-activity relationship study between baicalein and wogonin by spectrometry, molecular docking and microcalorimetry.

Flavones (e.g. baicalein and wogonin) extensively used worldwide in food preparation and traditional medicine. In this study, a systematically comparative study of their structure-activity relationships (SAR) on their interaction with BSA, antioxidant activity and antibacterial activity has been carried out by spectrometry, molecular docking and microcalorimetry. Our results show that the skeleton structure of flavones, the number of hydroxyl groups, the type of functional group, conjugated system and the steric hindrance may be responsible for their different biological activity. These findings not only would lay a scientific foundation for discovering and designing flavones-based food and drug, may also help us to understanding the structure-activity relationship between flavones at the molecular level.

Evaluation of radiofrequency safety by high temperature resolution MR thermometry using a paramagnetic lanthanide complex.

PURPOSE: The current practice of calculating the specific absorption rate (SAR) relies on local temperature measurements made using temperature probes. For an accurate SAR measurement, a temperature imaging method that provides high temperature sensitivity is desirable, because acceptable levels of SAR produce small temperature changes. MR thermometry using paramagnetic lanthanide complexes can be used to obtain absolute temperature measurements with sub-degree temperature and sub-millimeter spatial resolution. The aim of this study was to develop and evaluate a high temperature resolution MR technique to determine SAR. METHODS: MR thermometry using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene phosphonate) (TmDOTP(5-)), which has an almost 10(2) times stronger chemical shift temperature dependence than water, was used to develop a novel method for SAR measurement. Three-dimensional temperature and SAR images were calculated using MR images acquired with a conventional gradient recalled echo sequence and SAR-intensive T1ρ sequence. Effects of the presence of conducting wire and increasing T1ρ spin-lock pulse duration were also examined. RESULTS: SAR distribution could be visualized clearly and surges associated with conducting wires and increasing pulse duration were identified clearly in the computed high spatial resolution SAR images. CONCLUSION: A novel method with high temperature sensitivity is proposed as a tool to evaluate radiofrequency safety in MRI.