Abstract:
Proton NMR relaxation rates (R1 and R2) were measured in aqueous solutions of sucrose, d-glucose and d-fructose with increasing concentration. The measurements were carried out using Bruker PC 20 NMR Process Analyzer. Inversion recovery and CPMG pulse sequences are used for the measurement of relaxation rates. Results show that the values of relaxation rate increase as the concentration of the sugar is increased. The relaxation rate appears to be higher for sucrose solutions as compared to glucose or d-fructose solutions. These results were discussed on the basis of molecular association between sugar and water molecules through hydrogen bonding. The water self diffusion coefficient was measured in these sugar solutions by using pulse field gradient NMR method. As expected, the water self-diffusion coefficient was reduced with increased sugar concentrations. The results of translational mobility exhibited a higher mobility for fructose than glucose or sucrose in aqueous solutions.
The dependence of R2 on the inter-pulse delay of the CPMG sequence gives information on the proton exchange mechanism involved. The mechanism of exchange was studied using R2 with increasing inter pulse delay of 0.05–2.0 ms in aqueous solutions of 10%, 20% and 35% (w/v) of the above sugar solutions. From the plots of relaxation rates (R2) versus the 90°–180° pulse spacing it was possible to calculate the proton exchange rate (kb) of the different sugar solutions. Relaxation rates show characteristic variations with CPMG pulse spacing which can be interpreted on the basis of chemical exchange between solute and solvent molecules.
The experimental results namely relaxation rates and CPMG pulse spacing data show the importance of water interactions with sweet molecules and this can lead to a better understanding of the effect of hydration water in taste chemoreception.
Abstract: Irinotecan is an antitumor drug mostly used in the treatment of colorectal cancer. Its efficacy is influenced by the chemical state of the molecule undergoing chemical equilibria, metabolic changes and photodegradation. In this work, we describe the chemical equilibria of the drug in dimethyl sulfoxide (DMSO). The energetic barrier for hindered rotation around the bond connecting the piperidino—piperidino moiety with the camptothecin-like fragment was evaluated. Furthermore, we showed how the molecule aggregates in DMSO solution forming dimeric species able to prevent its degradation. The equilibrium constant for self-aggregation was determined by NMR based on the assumption of the isodesmic model. The formation of a dimer was highlighted by NMR diffusion ordered spectroscopy (NMR-DOSY) experiments at the concentrations used. Structural features of the complex were inferred by NOE and 13C chemical shift data. Molecular modelling of the complex driven by experimental data, lead to a structure implying the formation of two hydrogen bonds involving the lactone ring whose opening is one of the main causes of drug degradation. This species is probably responsible for the improved stability of the drug at concentrations higher than 1 mM.
Abstract: The Fourier Transform Infrared spectrum of (S)-4 ethyl-4-hydroxy-1H-pyrano [3',4':6,7]-indolizino-[1,2-b-quinoline-3,14-(4H,12H)-dione] [camptothecin] was recorded in the region 4000-400cm(-1). The Fourier Transform Raman spectrum of camptothecin (CPT) was also recorded in the region 3500-50cm(-1). Quantum chemical calculations of geometrical structural parameters and vibrational frequencies of CPT were carried out by MP2/6-31G(d,p) and density functional theory DFT/B3LYP/6-311++G(d,p) methods. The assignment of each normal mode has been made using the observed and calculated frequencies, their IR and Raman intensities. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR and FT-Raman spectra. Most of the computed frequencies were found to be in good agreement with the experimental observations. The isotropic chemical shifts computed by (13)C and (1)H NMR analysis also show good agreement with experimental observations. Comparison of calculated spectra with the experimental spectra provides important information about the ability of computational method to describe the vibrational modes of large sized organic molecule.
Abstract: The purpose of the present study was to isolate and characterize ailanthone-rich materials from the bark of the deciduous tree Ailanthus altissima and to assess their herbicide activity on selected herbaceous species. Ailanthone- rich fractions were obtained from A. altissima bark by extraction with dichloromethane and ethyl acetate and subsequent purification of these crude extracts, and of the remaining water mixture after solvent extraction, by means of gel permeation chromatography. A number of fractions were isolated and characterized for ailanthone content. A dichloromethane fraction was shown to contain 92% w/w of ailanthone as demonstrated by HPLC and NMR analysis. A significant pre-emergence herbicide activity was found for most of the extracts which was directly correlated to ailanthone concentration. A remarkable combined pre-emergence and post-emergence herbicide activity was found for a specific fraction. These results indicate that the bark of A. altissima may represent an interesting source for the production of natural herbicides for use in agriculture.
Abstract: The geometries, electronic structures, polarizabilities, and hyperpolarizabilities of organic dye sensitizer 4-Aminophthalonitrile were studied based on Hartee-Fock (HF) and Density Functional Theory (DFT) using the hybrid functional B3LYP. Ultraviolet-visible (UV-Vis) spectrum was investigated by Time Dependent DFT (TD-DFT). Features of the electronic absorption spectrum in the visible and near-UV regions were assigned based on TD-DFT calculations. The absorption bands have been assigned to n → π* transitions. Calculated results suggest that the three excited states with the lowest excited energies in 4-Aminophthalonitrile is due to photoinduced electron transfer processes. The interfacial electron transfer between semiconductor TiO2 electrode and dye sensitizer is due to an electron injection process from excited dye to the semiconductor’s conduction band. The role of cyanide and amine group in 4-Aminophthalonitrile geometries, electronic structures, and vibrational spectra were compared with experimental values and in view of these results, it was concluded that 4-Aminophthalonitrile used in Dye Sensitized Solar Cells (DSSC) gives a good conversion efficiency.
Abstract: The geometries, electronic structures, polarizabilities, and hyperpolarizabilities of organic dye sensitizers 3,4-pyridine-di-carbo-nitrile, 3-amino-phthalo-nitrile, 4-amino-phthalo-nitrile and 4-methyl-phthalo-nitrile were studied based on density functional theory using the hybrid functional B3LYP. Ultraviolet-visible spectra were investigated by time dependent density functional theory. The features of electronic absorption spectra in the visible and near-UV regions were assigned based on time dependent density functional theory calculations. The absorption bands are assigned to π → π* transitions. Calculated results suggest that the three lowest energy excited states of 3,4-pyridine-di-carbo-nitrile, 3-amino-phthalo-nitrile, 4-amino-phthalo-nitrile and 4-methyl-phthalo-nitrile are due to photoinduced electron transfer processes. The interfacial electron transfer between semiconductor TiO2 electrode and dye sensitizers 3,4-pyridine-di-carbo-nitrile, 3-amino-phthalo-nitrile, 4-amino-phthalo-nitrile and 4-methyl-phthalo-nitrile is due to an electron injection process from excited dyes to the semiconductor's conduction band. The role of amide and methyl groups in phthalonitrile in geometries, electronic structures, and spectral properties were analyzed in a comparative study of 3,4-pyridine-di-carbo-nitrile, 3-amino-phthalo-nitrile, 4-amino-phthalo-nitrile and 4-methyl-phthalo-nitrile for the improvement of dye sensitized solar cells.
Abstract: Carbon nanotube (CNTs) derivatives are nowadays under thorough investigation as biomedically interesting materials. In this paper we describe a method for the preparation of water-soluble CNTs by condensation of the carboxylic groups introduced onto the carbon framework and the primary amine moieties inserted in the naturally occurring biopolymer hyaluronan (HA). The covalent conjugation between CNTs and HA should merge the biocompatibility and further processability of the HA chains with the well-known cellular penetration properties of the CNT derivatives to produce novel drug delivery platforms. In fact, thanks to the primary amino groups introduced in the HA chains, HA–CNT derivatives can be further covalently modified with model drugs like ibuprofen and methotrexate. We describe also the monitoring of all the CNT derivatization steps by diffusion-ordered NMR spectroscopy (DOSY), a technique that allows fast and reliable characterization of these novel derivatives.
Abstract: The FT-IR and FT-Raman spectral studies of the Methotrexate (MTX) were carried out. The equilibrium geometry, various bonding features and harmonic vibrational frequencies of MTX have been investigated with the help of B3LYP density functional theory (DFT) using 6-31G(d) as basis set. Detailed analysis of the vibrational spectra has been made with the aid of theoretically predicted vibrational frequencies. The vibrational analysis confirms the differently acting ring modes, steric repulsion, conjugation and back-donation. The energy and oscillator strength calculated by Time-Dependent Density Functional Theory (TD-DFT) results complement with the experimental findings. The calculated HOMO and LUMO energies show that charge transfer occur within the molecule. Good correlations between the experimental (1)H and (13)C NMR chemical shifts in DMSO solution and calculated GIAO shielding tensors were found.
Abstract: Functionalized carbon nanotube (CNT) derivatives are currently under thorough investigation in different biomedical investigations. In this field of research, the composition of sample either in terms of covalently attached or physisorbed moieties can greatly affect the observed results and hamper the comparison between different studies. Therefore, the availability of a fast and reliable analytical technique to assess both the type of interaction (covalent vs noncovalent) and the composition of CNT conjugates is of great importance. Here we describe that the two-dimensional diffusion-ordered (DOSY) NMR spectroscopy is extremely useful to discriminate between conjugated and unconjugated polyethylene glycol groups in samples obtained by condensation with oxidized single-walled carbon nanotubes (SWNTs). This fast and nondestructive technique allows us to follow the removal of unconjugated polyethylene glycol chains during the purification. In particular, DOSY analysis reveal that about 1/3 (wt %) of the polyethylene glycol used for the condensation remained physisorbed to functionalized SWNTs after dialysis. Complete elimination of physisorbed polyethylene glycol was achieved using diafiltration.
Abstract: The UV-spectra of pure caffeine were measured and two quite differentiated hyper- or hypo-chromic effects were observed as concentration was increased. The first one was explained as due to caffeine-water molecule interaction and the second as originating from dimer formation and staking of caffeine molecules. The effects of sucrose and beta-cyclodextrin on the hydration and the self-association of caffeine were also examined by UV spectroscopy. Sucrose was found to enhance the self-association of caffeine molecules by attracting and structuring water molecules around itself. The caffeine-caffeine hydrophobic interactions were promoted in such hydrophilic environment and so was the stacking. The molecular aggregation leads to reducing the electronic mobility and so is the case for the mesomeric effect in the heterogeneous cycle. This could explain the hypo-chromic phenomenon observed when sucrose concentration was increased. beta-Cyclodextrin shows a distinct behaviour because of its ability to form inclusion complexes with various hydrophobic guest molecules. This ability enhances the solubility of caffeine molecules throughout the inclusion interactions and prevents the caffeine self-association.
Abstract: Selective halogenation of hyaluronan and partial halogen substitution by methotrexate led to 6-chloro-6-deoxy-6-O-methotrexylhyaluronan, a potential antitumor drug. The remaining halogen could be further substituted by a second organic carboxylate, leading to mixed esters. 6-O-Acetyl-6-O-methotrexylhyaluronan and 6-O-butyryl-6-O-methotrexylhyaluronan were thus synthesized and characterized by NMR spectroscopy.
Abstract: Benzoxazines are a class of phenolic compounds extensively studied in polymer science because of their properties as fiber reinforcements, fire-retardants and curing agents. In this article is described a solvent-less process, based on a Mannich reaction involving a primary amine and an aldehyde, for the preparation of new benzoxazines deriving from cardanol (a well known phenol obtained as a renewable organic resource and harmful by-product of the cashew industry). Particular attention is given to the synthesis and chemical characterization (both by 1H NMR spectroscopy and HPLC), while the thermal polymerization process has been monitored by differential scanning calorimetry.
Abstract: A novel methodology for making drug conjugates using hyaluronan as a carrier was developed. This strategy involves a completely regioselective two-step synthesis of 6-amino-6-deoxyhyaluronan, which is then easily functionalized with drugs through a suitable linker. The case of hyaluronan-camptothecin conjugates is described, making use of a simple succinate linker. The antitumor activity of new hyaluronan derivatives prepared is at present under evaluation.
Abstract: The emerging applications of functionalized carbon nanotubes (CNTs) in various research domains necessitate the use of many different analytical techniques to confirm their structural modifications in a fast and reliable manner. Thus far, NMR spectroscopy has not been among the main tools for characterization of organically modified carbon nanostructures. (1)H analysis is limited because the signals in these derivatives are typically weak and broad, resulting in uncertainties of a few parts per million, and because of the strong interference of residual solvent signals. To overcome these limitations, we investigated the applicability of proton NMR spectroscopy based on gradient-edited diffusion pulse sequences (1D diffusion-ordered spectroscopy, DOSY) in the characterization of CNT derivatives. In general, diffusion NMR experiments allow the separation of NMR signals of different species present in a mixture, according to their own diffusion coefficients, merging spectroscopy information with size analysis. In the present study, a selected set of CNT derivatives was synthesized and analyzed using 1D DOSY experiments by applying strong magnetic field gradients (up to 42.6 G cm(-1)). Colorimetric tests (i.e., Kaiser test) and TGA analysis support the NMR findings, which are related to isolated and/or bundled short SWNTs, on the basis of TEM and AFM characterization. The overall results show that the diffusion-based NMR spectroscopy is a fast and promising approach for the characterization of covalently modified CNT derivatives.
Abstract: Sweet and bitter tastes are known to be mediated by G-protein-coupled receptors. The relationship between the chemical structure of gustable molecules and their molecular organization in saliva (aqueous solution) near the surface of the tongue provides a useful tool for elucidating the mechanism of chemoreception. The interactions between stimulus and membrane receptors occur in an anisotropic system. They might be influenced by the molecular packing of gustable molecules within an aqueous solvent (saliva) close to the receptor protein. To investigate the molecular organization of a sweet molecule (sucrose), a bitter molecule (caffeine), and their mixture in an aqueous phase near a "wall", a hydrophobic phase, we modeled this using an air/liquid interface as an anisotropic system. The experimental (tensiometry and ellipsometry) data unambiguously show that caffeine molecules form an adsorption layer, whereas sucrose induces a desorption layer at the air/water interface. The adsorption of caffeine molecules at the air/water interface gradually increases with the volume concentration and is delayed when sucrose is added to the solution. Spectroscopic ellipsometry data show that caffeine in the adsorption layer has optical properties practically identical to those of the molecule in solution. The results are interpreted in terms of molecular association of caffeine with itself at the interface with and without sucrose in the subphase, using the theory of ideal gases.
Abstract: Solution properties of sapid molecules are informative on their type of hydration (hydrophobic or hydrophilic) and on the extent of the hydration layer. Physicochemical properties (intrinsic viscosity and apparent specific volume) and nuclear magnetic resonance (NMR) relaxation rates R(1) and R(2) for pure sucrose, bitter molecule caffeine, and their mixture were found to be relevant in the interpretation of the effects of these solutes on water mobility. Likewise, surface tension, contact angles with a hydrophobic surface, and the adhesion forces to this type of surface of the aqueous solutions of sapid molecules were found to discriminate between their effects on water cohesion and also between their taste qualities. The interpretation of the two sets of independent experimental results, namely physicochemical and spectroscopic data, helps in the elucidation of the role of water in sweet and bitter taste chemoreception.
Abstract: The Proton magnetic Resonance (PMR) spin-lattice and spin-spin relaxation times (T1 and T2) were measured in highly viscous (glycerine - water) and less viscous (dioxan-water) systems at different temperatures. The values of relaxation times increase with increasing the temperature. This result is interpreted as due to the combined effect of viscosity and temperature in these solutions. The relaxation times were also measured in these solutions containing paramagnetic ions(PMI). The results indicate that the possibility of an anti-parallel bonding of the paramagnetic ions is higher in highly viscous solutions as compared to low viscous systems and the association in the above mixtures appears to be weak.
Abstract: Density and ultrasonic velocity were measured in aqueous solutions of sodium, potassium and magnesium gluconate as a function of increasing concentration. Apparent molar volume (AMV), apparent specific volume (ASV), isentropic apparent molar (IAMC) compressibility and hydration numbers were calculated from the experimental data. The results show that AMV and ASV increase as the concentration of gluconates is increased. This is interpreted on the basis of molecular interaction between solute and solvent molecules. These measurements were repeated by adding Na, K and Mg gluconates to 10 and 20% sucrose solution with the aim of understanding the influence of gluconates on water association in sucrose solutions. The results show that the values of IAMC decrease as the concentration is increased. Moreover, Mg gluconate shows more negative IAMC than Na and K gluconates. The observed results are explained on the basis of the hydration of gluconates in the sucrose-water system. NMR relaxation rates (R1 and R2) show an increase as the concentration of the gluconate is increased. On the other hand, the results of Na, K and Mg gluconate in 10 and 20% sucrose solutions demonstrated that the effect of Mg gluconate enhances the hydration properties of sucrose water mixtures more than Na and K gluconate. The overall results show the importance of water interactions with sapid molecules and this can lead to a better understanding of their tastes.
Abstract: The 2-methylglutamic acid (2M) analogue was generally inactive in electrophysiological experiments and had generally worse functional activity. The low functional activity obtained with 2M would not be determined by only α substitution or C methylation, since the extensive biological studies of α,α‘-dialkyl cyclic analogues of glutamic acid containing a cyclohexane and a cyclopentane ring or β- or γ-methylated glutamic acid analogues with linear flexible systems have indicated interesting properties. A conformational analysis by 1H and 13C NMR spectroscopy and molecular modeling of 2M was undertaken in aqueous solution to identify the preferred solution conformations and to understand whether its different biological activities would be due to structural differences. The preferred conformation of the 2M molecule is the sterically favored one Ca, corresponding to a large “W†between the methyl and the carboxylate groups mixed with Aa showing a large zig−zag alkylamine chain ending in a carboxylate group, or Ba, corresponding to a large “W†between the amino and the carboxylate groups.
Abstract: In the present study, the conformational behaviour of methyl substituted N-BOC glutamic acid methyl esters (2M, 3T, 3E, 4T, 4E) has been completely characterized through combined NMR and molecular modeling studies. Hetero- and homonuclear coupling constants were measured in order to assign the remaining diastereotopic methylene protons at C(3) and/or C(4), and used for comparison with theoretical data. In parallel, the complete conformational analysis of these analogues has been achieved using molecular mechanics and molecular dynamics (MD) methods. The conformation of the glutamyl residue is established by the excellent agreement between the experimental and calculated side chain scalar coupling constants. The theoretical NMR data were calculated taking into account all the accessible conformations and using the averaging methods appropriate for internal motions. There is a significant influence of the methyl group on the conformational behaviour and on the biological relevance of these structures. Steric effect or electrostatic interaction may also have a considerable influence in stabilizing a conformational population in D2O solution. The conformational preferences of those different analogues in aqueous and methanol solution are discussed in the light of biological results obtained on the vitamin K-dependent carboxylase system.
Abstract: Liver cell necrosis was induced in rats by a galactosamine injection. Cell death was due to an increase of Ca++ intracellular levels and was also under the control of genes. Rats were then either exposed or not to a 6 mT 100 HZ pulsed magnetic field (PMF) and they either received or not methylsilane-triol injections. Animals were sacrificed twenty-seven hours after a galactosamine injection. On the one hand it appeared from transaminase levels that the PMF increased the number of animals which were sensitized to galactosamine but decreased transaminase levels. On the other hand PMF decreased the protective effect of MST against galactosamine. We may suggest that PMF should be considered as an additional cellular signal received through genes which would determine the evolution towards or against apoptosis according to the age of the cell itself but also the Ca++ intracellular level.
Abstract: The proton magnetic resonance (PMR) spin-lattice and spin-spin relaxation times (T1 and T2) were measured in aqueous solutions of glycine and L-proline as a function of solute concentrations and at a temperature of 32°C. The relaxation times were measured using Bruker PC 120 NMR process analyser. The relaxation times were found to decrease with increase of solute concentrations. The results are interpreted on the basis of flickering cluster model and hydrogen bond formation between solute and solvent molecules.
Abstract: Proton Magnetic Resonance (PMR) spin-lattice relaxation times (T1) were measured in aqueous solutions of maltose and galactose in the concentration range 0-2 molar and at a temperature of 37° C. The spin-lattice relaxation time (T1) is found to decrease with the increase of sugar concentration. On the otherhand, the relaxation time is found to be lower for maltose solutions as compared to galactose solutions. These results were discussed on the basis of molecular association between sugar and water molecules through hydrogen bonding and the two-state fast exchange model of water molecules.
Abstract: The proton magnetic resonance (PMR) spin-lattice relaxation times (T1) were measured in aqueous solutions of glucose and sucrose. T1 was found to decrease with increase of sugar concentration. This result is interpreted as due to molecular association between sugar and water molecules. The relaxation times were also measured in aqueous solutions of alkali halides containing glucose and sucrose to study the influence of sugar on the relaxation times. The results are interpreted in terms of structure making and breaking properties of alkali ions.
Abstract: Proton Magnetic Resonance (PMR) relaxation time measurements were performed in aqueous solutions of maltose and galactose as a function of sugar and alkali halide concentration. The experimental data unambiguously show that the presence of alkali halides highly influences the PMR relaxation process. The nature of molecular interaction in this ternary system is explained on the basis of two state fast exchange model and structure ordering/disordering of alkali halides.
Abstract: Proton NMR relaxation times T1 and T2 were measured in methonal, ethanol, propanol and butanol at a temperature of 37°C and at an RF frequency of 20 MHz. The hydrogen bond energies of the above alcohols are in the range 2.33-4.56 Kcal/mole. The relaxation time T1 is found to decrease with increase of hydrogen bond energy in these alcohols and this is explained by postulating mutal interactions between adjacent hydrogen bonds.
Abstract: Proton magnetic relexation times(T1 & T2) were measured for over 80 malignant and normal tissue samples of various organs of human body such as uterus, stomach, thyroid, thigh and cervix. The measurements were carried out at an RF frequency of 20 MHz using Brucker PC 120 NMR process analyser. The percentageof water content was also measured for all the tissue samples. In general the spin-lattice relaxation time(T1) values were found to be longer for malignant tissue as compared to normal tissue whereas the spin-spin relaxation time(T2) values do not exhibit the above trend. The molecular interactions that are likely to be responsible for the increased values of T1 in cancerous tissues (as compared to normal ones) will be discussed in the paper.
Abstract: The proton magnetic resonance (PMR) spin-lattice relaxation times (T1) were measured in aqueous solution of fructose. T1 was found to decrease with increase of fructose concentration. This result is interpreted as due to molecular association between the fructose and water molecules. The relaxation times T1 were also measured in aqueous solutions of alkali halides containing the sugar fructose to study the influence of this sugar on the relaxation times. The results are interpreted in terms of structure making and breaking properties of alkali ions.
Abstract: Proton magnetic resonance (PMR) relaxation times were measured for dissected malignant and normal tissue derived from breast cancer patients. Relaxation time measurements (T1, T2) were carried out at a RF frequency of 20 MHz and at a temperature of 27 degrees C with a Brucker PC 120 NMR Process analyser. The tissue types were confirmed by histopathological examination. In general T1 values were found to be longer for malignant tissues as compared to normal tissues which is in agreement with the earlier observations. The measured T2 values do not exhibit the malignant tissues above. The percentage of water content was also measured in both normal and malignant tissue and was found to be considerably larger in tumour tissue as compared to normal tissue. These results are discussed on the basis of two fraction fast exchange models of water molecules and confirm that PMR relaxation time measurement plays an important role in the differentiation of cancerous tissues from that of normal.
