scholarly journals Gd3+ Complexes Conjugated to Cyclodextrins: Hydroxyl Functions Influence the Relaxation Properties

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 269
Author(s):  
Anais Biscotti ◽  
François Estour ◽  
Berthe-Sandra Sembo-Backonly ◽  
Sébastien Balieu ◽  
Michaël Bosco ◽  
...  
Keyword(s):  
Water Molecule ◽  
Bound Water ◽  
Relaxation Dispersion ◽  
Amide Bond ◽  
Hydroxyl Groups ◽  
Relaxation Rates ◽  
Transverse Relaxation ◽  
Relaxation Properties ◽  
Hydrogen Bound ◽  
The Impact

In the search for improvement in the properties of gadolinium-based contrast agents, cyclodextrins (CDs) are interesting hydrophilic scaffolds with high molecular weight. The impact of the hydrophilicity of these systems on the MRI efficacy has been studied using five β-CDs substituted with DOTA or TTHA ligands which, respectively, allow for one (q = 1) or no water molecule (q = 0) in the inner coordination sphere of the Gd3+ ion. Original synthetic pathways were developed to immobilize the ligands at C-6 position of various hydroxylated and permethylated β-CDs via an amide bond. To describe the influence of alcohol and ether oxide functions of the CD macrocycle on the relaxation properties of the Gd3+ complexes, 1H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles, and 17O transverse relaxation rates have been measured at various temperatures. The differences observed between the hydroxylated and permethylated β-CDs bearing non-hydrated GdTTHA complexes can be rationalized by a second sphere contribution to the relaxivity in the case of the hydroxylated derivatives, induced by hydrogen-bound water molecules around the hydroxyl groups. In contrast, for the DOTA analogs the exchange rate of the water molecule directly coordinated to the Gd3+ is clearly influenced by the number of hydroxyl groups present on the CD, which in turn influences the relaxivity and gives rise to a very complex behavior of these hydrophilic systems.

scholarly journals Expanding the Ligand Classes Used for Mn(II) Complexation: Oxa-aza Macrocycles Make the Difference

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1524
Author(s):  
Ferenc K. Kálmán ◽  
Viktória Nagy ◽  
Rocío Uzal-Varela ◽  
Paulo Pérez-Lourido ◽  
David Esteban-Gómez ◽  
...  
Keyword(s):  
Water Molecule ◽  
Metal Ion ◽  
Macrocyclic Ligand ◽  
Relaxation Dispersion ◽  
Metal Exchange ◽  
Relaxation Rates ◽  
Exchange Reactions ◽  
Biologically Relevant ◽  
The Difference ◽  
Nuclear Magnetic

We report two macrocyclic ligands based on a 1,7-diaza-12-crown-4 platform functionalized with acetate (tO2DO2A2−) or piperidineacetamide (tO2DO2AMPip) pendant arms and a detailed characterization of the corresponding Mn(II) complexes. The X−ray structure of [Mn(tO2DO2A)(H2O)]·2H2O shows that the metal ion is coordinated by six donor atoms of the macrocyclic ligand and one water molecule, to result in seven-coordination. The Cu(II) analogue presents a distorted octahedral coordination environment. The protonation constants of the ligands and the stability constants of the complexes formed with Mn(II) and other biologically relevant metal ions (Mg(II), Ca(II), Cu(II) and Zn(II)) were determined using potentiometric titrations (I = 0.15 M NaCl, T = 25 °C). The conditional stabilities of Mn(II) complexes at pH 7.4 are comparable to those reported for the cyclen-based tDO2A2− ligand. The dissociation of the Mn(II) chelates were investigated by evaluating the rate constants of metal exchange reactions with Cu(II) under acidic conditions (I = 0.15 M NaCl, T = 25 °C). Dissociation of the [Mn(tO2DO2A)(H2O)] complex occurs through both proton− and metal−assisted pathways, while the [Mn(tO2DO2AMPip)(H2O)] analogue dissociates through spontaneous and proton-assisted mechanisms. The Mn(II) complex of tO2DO2A2− is remarkably inert with respect to its dissociation, while the amide analogue is significantly more labile. The presence of a water molecule coordinated to Mn(II) imparts relatively high relaxivities to the complexes. The parameters determining this key property were investigated using 17O NMR (Nuclear Magnetic Resonance) transverse relaxation rates and 1H nuclear magnetic relaxation dispersion (NMRD) profiles.

Depth profiles of hydrogen bound water molecule types and their relation to lipid and protein interaction in the human stratum corneum in vivo

The Analyst ◽  
2016 ◽  
Vol 141 (22) ◽  
pp. 6329-6337 ◽  
Author(s):  
ChunSik Choe ◽  
Jürgen Lademann ◽  
Maxim E. Darvin
Keyword(s):  
Hydrogen Bonding ◽  
Water Molecule ◽  
Gaussian Function ◽  
Bound Water ◽  
Confocal Raman Microscopy ◽  
Depth Profiles ◽  
Confocal Raman ◽  
Hydrogen Bound ◽  
Water Profile

Confocal Raman microscopy has been used to measure the depth-dependent profiles of hydrogen bound water molecule types in human SCin vivousing the Gaussian function-based deconvolution procedure of the HWN region. The hydrogen bonding state of the water profile in the SC has been determined.

Measurement, analysis and prediction of amoxicillin oral dose stability from integrated molecular description approach and accelerated predictive stability (APS)

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Camille Merienne ◽  
Chloe Marchand ◽  
Samira Filali ◽  
Damien Salmon ◽  
Christine Pivot ◽  
...  
Keyword(s):  
Oral Dose ◽  
Shelf Life ◽  
Chromatographic Analysis ◽  
Water Adsorption ◽  
Degradation Mechanism ◽  
Oral Dosage ◽  
Hydroxyl Groups ◽  
Humid Atmosphere ◽  
Intramolecular Hydrogen ◽  
The Impact

AbstractBackgroundStability of low amoxicillin oral dosage form (5 mg) used in reintroduction drug test was not fully documented. Furthermore, the impact of (1) salt moiety of amoxicillin and (2) amoxicillin – excipient interactions upon the antibiotic formulation stability during the storage was not characterized so that the estimation of the pharmaceutical expiration date from shelf-life was uncertain. Thus, the main goal of this study was to estimate the shelf-life of two formulations of amoxicillin, using a semi-predictive methodology.MethodsAmoxicillin sodium (AS) and amoxicillin trihydrate (ATH), corresponding to 5-mg amoxicillin, were compounded with microcrystalline cellulose (MCC) in oral hard capsules which were, then, submitted to four environmental conditions (25 °C / 60% or 80% relative humidity (RH); 40 °C / 75% RH; 60 °C / 5% RH) in climatic chambers for 45 and 84 days. Therefore, the characterization of amoxicillin-MCC mixture was assessed by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) The profiles of amoxicillin content (determined by stability indicating chromatographic method) as a function of storage time, temperature and RH were fitted to pre-defined kinetic models performed by accelerated predictive stability (APS).ResultsATR-FTIR analysis of AS, ATH, MCC and bulk specimens stored in heated and humid atmosphere confirmed water sorption to cellulose described by a broad and unresolved 3600 to 3000 cm−1 band associated with (1) general intramolecular and intermolecular hydrogen bonding between water and hydroxyl groups of the cellulose, and with (2) free hydroxyl in cellulose. Moreover, a dramatic decrease of absorption at 1776 and 1687 cm−1 respectively characteristic of the β-lactam ring (νC=O) and amide group (νC=O), was revealed as a consequence of AS and ATH degradation caused by moisturization of bulk. Amoxicillin degradation was established by chromatographic analysis showing faster AS degradation than ATH throughout time exposure. The combined effects of temperature – RH were successfully modeled by APS, where AS and ATH showed accelerated (auto-catalysis degradation mechanism) and linear degradation, respectively. The faster AS degradation was assumed to be linked to lower hydrogen donor to hydrogen acceptor count ratio and polar surface than ATH, increasing the probability of AS hydrolysis by water adsorption to AS-MCC solid dispersion (e.g., by reduction of protective intramolecular hydrogen bonds between AS molecules). Furthermore, the compounding which involved a drastic homogenization of solids may have affected the crystalline degree of MCC with an increase of amorphous phase more sensitive to water adsorption.ConclusionsThe improvement of amoxicillin compounding for oral dose forms might be rationalized by taking into account the molecular descriptors of salt moiety and excipients, improved by the choice of an appropriate process of production, characterized from infrared vibrational spectroscopy and chromatographic analysis and finally predicted from accelerated stability assays.

Crystal structure of atropine sulfate monohydrate, (C17H24NO3)2(SO4)·(H2O)

2019 ◽  
Vol 34 (4) ◽  
pp. 389-395 ◽  
Author(s):  
James A. Kaduk ◽  
Amy M. Gindhart ◽  
Thomas N. Blanton
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
Water Molecule ◽  
Powder Diffraction ◽  
Density Functional ◽  
Atropine Sulfate ◽  
Strong Hydrogen Bond ◽  
Hydroxyl Groups ◽  
Hydrogen Atoms ◽  
Sulfate Anion

The crystal structure of atropine sulfate monohydrate has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Atropine sulfate monohydrate crystallizes in space group P21/n (#14) with a = 19.2948(5), b = 6.9749(2), c = 26.9036(5) Å, β = 94.215(2)°, V = 3610.86(9) Å3, and Z = 4. Each of the two independent protonated nitrogen atoms participates in a strong hydrogen bond to the sulfate anion. Each of the two independent hydroxyl groups acts as a donor in a hydrogen bond to the sulfate anion, but only one of the water molecule hydrogen atoms acts as a hydrogen bond donor to the sulfate anion. The hydrogen bonds are all discrete but link the cations, anion, and water molecule along [101]. Although atropine and hyoscyamine (atropine is racemic hyoscyamine) crystal structures share some features, such as hydrogen bonding and phenyl–phenyl packing, the powder patterns show that the structures are very different. The powder pattern for atropine sulfate monohydrate has been submitted to ICDD for inclusion in the Powder Diffraction File™.

scholarly journals Proline-rich domain of human ALIX contains multiple TSG101-UEV interaction sites and forms phosphorylation-mediated reversible amyloids

2020 ◽  
Vol 117 (39) ◽  
pp. 24274-24284
Author(s):  
Ruben D. Elias ◽  
Wen Ma ◽  
Rodolfo Ghirlando ◽  
Charles D. Schwieters ◽  
Vijay S. Reddy ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Amyloid Fibrils ◽  
Recombinant Expression ◽  
Hydrophobic Effect ◽  
Adaptor Protein ◽  
Relaxation Dispersion ◽  
Divide And Conquer ◽  
Interaction Sites ◽  
Rich Domain ◽  
The Impact

Proline-rich domains (PRDs) are among the most prevalent signaling modules of eukaryotes but often unexplored by biophysical techniques as their heterologous recombinant expression poses significant difficulties. Using a “divide-and-conquer” approach, we present a detailed investigation of a PRD (166 residues; ∼30% prolines) belonging to a human protein ALIX, a versatile adaptor protein involved in essential cellular processes including ESCRT-mediated membrane remodeling, cell adhesion, and apoptosis. In solution, the N-terminal fragment of ALIX-PRD is dynamically disordered. It contains three tandem sequentially similar proline-rich motifs that compete for a single binding site on its signaling partner, TSG101-UEV, as evidenced by heteronuclear NMR spectroscopy. Global fitting of relaxation dispersion data, measured as a function of TSG101-UEV concentration, allowed precise quantitation of these interactions. In contrast to the soluble N-terminal portion, the C-terminal tyrosine-rich fragment of ALIX-PRD forms amyloid fibrils and viscous gels validated using dye-binding assays with amyloid-specific probes, congo red and thioflavin T (ThT), and visualized by transmission electron microscopy. Remarkably, fibrils dissolve at low temperatures (2 to 6 °C) or upon hyperphosphorylation with Src kinase. Aggregation kinetics monitored by ThT fluorescence shows that charge repulsion dictates phosphorylation-mediated fibril dissolution and that the hydrophobic effect drives fibril formation. These data illuminate the mechanistic interplay between interactions of ALIX-PRD with TSG101-UEV and polymerization of ALIX-PRD and its central role in regulating ALIX function. This study also demonstrates the broad functional repertoires of PRDs and uncovers the impact of posttranslational modifications in the modulation of reversible amyloids.

scholarly journals Transverse relaxation rates of pulmonary dissolved‐phase Hyperpolarized 129 Xe as a biomarker of lung injury in idiopathic pulmonary fibrosis

2020 ◽  
Vol 84 (4) ◽  
pp. 1857-1867
Author(s):  
Jeff Kammerman ◽  
Andrew D. Hahn ◽  
Robert V. Cadman ◽  
Annelise Malkus ◽  
David Mummy ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Relaxation Rates ◽  
Transverse Relaxation ◽  
Dissolved Phase

scholarly journals In Vivo Quantification of Cerebral R2*-Response to Graded Hyperoxia at 3 Tesla

2015 ◽  
Vol 5 ◽  
pp. 1 ◽  
Author(s):  
Grigorios Gotzamanis ◽  
Roman Kocian ◽  
Pinar S. Özbay ◽  
Manuel Redle ◽  
Spyridon Kollias ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Relaxation Rate ◽  
Tumor Therapy ◽  
Cerebrovascular Reactivity ◽  
Oxygen Intake ◽  
Transverse Relaxation Rate ◽  
Dependent Manner ◽  
Relaxation Rates ◽  
Transverse Relaxation ◽  
Arterial Blood

Objectives: This study aims to quantify the response of the transverse relaxation rate of the magnetic resonance (MR) signal of the cerebral tissue in healthy volunteers to the administration of air with step-wise increasing percentage of oxygen. Materials and Methods: The transverse relaxation rate (R2*) of the MR signal was quantified in seven volunteers under respiratory intake of normobaric gas mixtures containing 21, 50, 75, and 100% oxygen, respectively. End-tidal breath composition, arterial blood saturation (SaO2), and heart pulse rate were monitored during the challenge. R2* maps were computed from multi-echo, gradient-echo magnetic resonance imaging (MRI) data, acquired at 3.0T. The average values in the segmented white matter (WM) and gray matter (GM) were tested by the analysis of variance (ANOVA), with Bonferroni post-hoc correction. The GM R2*-reactivity to hyperoxia was modeled using the Hill's equation. Results: Graded hyperoxia resulted in a progressive and significant (P < 0.05) decrease of the R2* in GM. Under normoxia the GM-R2* was 17.2 ± 1.1 s-1. At 75% O2 supply, the R2* had reached a saturation level, with 16.4 ± 0.7 s-1 (P = 0.02), without a significant further decrease for 100% O2. The R2*-response of GM correlated positively with CO2 partial pressure (R = 0.69 ± 0.19) and negatively with SaO2 (R = -0.74 ± 0.17). The WM showed a similar progressive, but non-significant, decrease in the relaxation rates, with an increase in oxygen intake (P = 0.055). The Hill's model predicted a maximum R2* response of the GM, of 3.5%, with half the maximum at 68% oxygen concentration. Conclusions: The GM-R2* responds to hyperoxia in a concentration-dependent manner, suggesting that monitoring and modeling of the R2*-response may provide new oxygenation biomarkers for tumor therapy or assessment of cerebrovascular reactivity in patients.

scholarly journals High-Resolution CMRO2 Mapping in Rat Cortex: A Multiparametric Approach to Calibration of BOLD Image Contrast at 7 Tesla

2000 ◽  
Vol 20 (5) ◽  
pp. 847-860 ◽  
Author(s):  
Ikuhiro Kida ◽  
Richard P. Kennan ◽  
Douglas L. Rothman ◽  
Kevin L. Behar ◽  
Fahmeed Hyder
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Spin Echo ◽  
7 Tesla ◽  
Relaxation Rates ◽  
Resonance Imaging ◽  
Gradient Echo ◽  
Transverse Relaxation ◽  
Physiologic Parameters ◽  
Spin Echo Sequences

The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) method, which is sensitive to vascular paramagnetic deoxyhemoglobin, is dependent on regional values of cerebral metabolic rate of oxygen utilization (CMRO2), blood flow (CBF), and volume (CBV). Induced changes in deoxyhemoglobin function as an endogenous contrast agent, which in turn affects the transverse relaxation rates of tissue water that can be measured by gradient-echo and spin-echo sequences in BOLD fMRI. The purpose here was to define the quantitative relation between BOLD signal change and underlying physiologic parameters. To this end, magnetic resonance imaging and spectroscopy methods were used to measure CBF, CMRO2, CBV, and relaxation rates (with gradient-echo and spin-echo sequences) at 7 Tesla in rat sensorimotor cortex, where cerebral activity was altered pharmacologically within the autoregulatory range. The changes in tissue transverse relaxation rates were negatively and linearly correlated with changes in CBF, CMRO2, and CBV. The multiparametric measurements revealed that CBF and CMRO2 are the dominant physiologic parameters that modulate the BOLD fMRI signal, where the ratios of (ΔCMRO2/CMRO2)/(ΔCBF/CBF) and (ΔCBV/CBV)/(ΔCBF/CBF) were 0.86 ± 0.02 and 0.03 ± 0.02, respectively. The calibrated BOLD signals (spatial resolution of 48 μL) from gradient-echo and spin-echo sequences were used to predict changes in CMRO2 using measured changes in CBF, CBV, and transverse relaxation rates. The excellent agreement between measured and predicted values for changes in CMRO2 provides experimental support of the current theory of the BOLD phenomenon. In gradient-echo sequences, BOLD contrast is affected by reversible processes such as static inhomogeneities and slow diffusion, whereas in spin-echo sequences these effects are refocused and are mainly altered by extravascular spin diffusion. This study provides steps by which multiparametric MRI measurements can be used to obtain high-spatial resolution CMRO2 maps.

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