Modulation of water proton relaxation rates by liposomes containing paramagnetic materials

1988 ◽  
Vol 6 (4) ◽  
pp. 445-458 ◽  
Author(s):  
G. Bačić ◽  
M. R. Niesman ◽  
H. F. Bennett ◽  
R. L. Magin ◽  
H. M. Swartz
Keyword(s):  
Water Proton ◽  
Proton Relaxation ◽  
Relaxation Rates ◽  
Paramagnetic Materials

scholarly journals Revisiting paramagnetic relaxation enhancements in slowly rotating systems: how long is the long range?

2020 ◽  
Author(s):  
Giovanni Bellomo ◽  
Enrico Ravera ◽  
Vito Calderone ◽  
Mauro Botta ◽  
Marco Fragai ◽  
...  
Keyword(s):  
Chemical Exchange ◽  
Protein Structure Determination ◽  
Bulk Water ◽  
Water Proton ◽  
Proton Relaxation ◽  
Relaxation Rates ◽  
Rotating Systems ◽  
Complete Relaxation ◽  
Nuclear Magnetization ◽  
Order Of Magnitude

Abstract. Cross relaxation terms in paramagnetic systems that reorient rigidly with slow tumbling times can increase the effective longitudinal relaxation rates of protons of more than one order of magnitude. This is evaluated by simulating the time evolution of the nuclear magnetization using a complete relaxation matrix approach. The calculations show that the Solomon dependence of the relaxation rates on the metal-proton distance (as r−6) can be incorrect for protons farther than 15 Å from the metal, and thus can originate sizable errors in R1-derived distance restraints used, for instance, for protein structure determination. Furthermore, the chemical exchange of these protons with bulk water protons can enhance the relaxation rate of the solvent protons by far more than expected from the Solomon equation. Therefore, it may contribute significantly to the water proton relaxation rates measured at MRI magnetic fields in the presence of slow-rotating nanoparticles containing paramagnetic ions and a large number of exchangeable surface protons.

scholarly journals The binding of lanthanides to non-immune rabbit immunoglobulin G and its fragments

1975 ◽  
Vol 149 (1) ◽  
pp. 73-82 ◽  
Author(s):  
S K Dower ◽  
R A Dwek ◽  
A C McLaughlin ◽  
L E Mole ◽  
E M Press ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Immunoglobulin G ◽  
Metal Binding ◽  
Binding Sites ◽  
Water Proton ◽  
Proton Relaxation ◽  
Relaxation Rates ◽  
Protein Fluorescence ◽  
Chain Dimer ◽  
Rabbit Igg

The binding of Gd(III) to rabbit IgG (immunoglobulin G) and the Fab (N-terminal half of heavy and light chain), (Fab')2 (N-terminal half of heavy and light chains joined by inter-chain disulphide bond), Fc (C-terminal half of heavy-chain dimer)and pFc' (C-terminal quarter of heavy-chain dimer) fragments was demonstrated by measurements of the enhancement of the solvent-water proton relaxation rates in the appropriate Gd(III) solutions. At pH 5.5 there are six specific Gd(III)-binding sites on the IgG. These six sites can be divided into two classes; two very ‘tight’ sites on the Fc fragment (Kd approx. 5 μM) and two weaker sites on each Fab region (Kd approx. 140 μM). Ca(II) does not apparently compete for these metal-binding sites. The metal-binding parameters for IgG can be explained as the sum of the metal binding to the isolated Fab and Fc fragments, suggesting that there is no apparent interaction between the Fab and Fc regions in the IgG molecule. The binding of Gd(III) to Fab and Fc fragments was also monitored by measuring changes in the electron-spin-resonance spectrum of Gd(III) in the presence of each fragment and also by monitoring the effects of Gd(III) on the protein fluorescence at 340 nm (excitation 295 nm). The fluorescence of Tb(III) solutions of 545 nm (excitation 295 nm) is enhanced slightly on addition of Fab or Fc.

scholarly journals Revisiting paramagnetic relaxation enhancements in slowly rotating systems: how long is the long range?

2021 ◽  
Vol 2 (1) ◽  
pp. 25-31
Author(s):  
Giovanni Bellomo ◽  
Enrico Ravera ◽  
Vito Calderone ◽  
Mauro Botta ◽  
Marco Fragai ◽  
...  
Keyword(s):  
Relaxation Rate ◽  
Chemical Exchange ◽  
Protein Structure Determination ◽  
Bulk Water ◽  
Paramagnetic Relaxation ◽  
Water Proton ◽  
Proton Relaxation ◽  
Relaxation Rates ◽  
Rotating Systems ◽  
Order Of Magnitude

Abstract. Cross-relaxation terms in paramagnetic systems that reorient rigidly with slow tumbling times can increase the effective longitudinal relaxation rates of protons of more than 1 order of magnitude. This is evaluated by simulating the time evolution of the nuclear magnetization using a complete relaxation rate-matrix approach. The calculations show that the Solomon dependence of the paramagnetic relaxation rates on the metal–proton distance (as r−6) can be incorrect for protons farther than 15 Å from the metal and thus can cause sizable errors in R1-derived distance restraints used, for instance, for protein structure determination. Furthermore, the chemical exchange of these protons with bulk water protons can enhance the relaxation rate of the solvent protons by far more than expected from the paramagnetic Solomon equation. Therefore, it may contribute significantly to the water proton relaxation rates measured at magnetic resonance imaging (MRI) magnetic fields in the presence of slow-rotating nanoparticles containing paramagnetic ions and a large number of exchangeable surface protons.

scholarly journals The use of gadolinium as a probe in the Fc region of a homogeneous anti-(type-III pneumococcal polysaccharide) antibody

1977 ◽  
Vol 161 (2) ◽  
pp. 205-211 ◽  
Author(s):  
K J Willan ◽  
K H Wallace ◽  
J C Jaton ◽  
R A Dwek
Keyword(s):  
Water Proton ◽  
Proton Relaxation ◽  
Relaxation Rates ◽  
Fab Fragment ◽  
Fc Fragment ◽  
Type Iii ◽  
Solvent Water ◽  
Specificity Of Binding ◽  
Polysaccharide Antibody ◽  
Antigen Antibody

The binding of gadolinium [Gd(III)] to a homogeneous rabbit anti-(type-III pneumococcal polysaccharide) IgG (immunoglobulin G) and its Fab (N-terminal half of heavy and light chain) and Fc (C-terminal half of heavy-chain dimer) fragments was demonstrated by measurements of solvent-water proton relaxation rates in the appropriate Gd(III) solutions. At pH 5.5 the binding of Gd(III) to the Fc fragment is much tighter (KD approx. 5 micronM) than binding to the Fab fragment (KD approx. 250 micronM). The binding of Gd(III) to the whole IgG molecule (KD approx. 4 micronM) is very similar to that for the Fc fragment alone. This specificity of binding to the Fc region allows the use of Gd(III) as a probe of the Fc conformation. The environment of the Gd(III) in the Fc region of whole IgG is not affected by the presence of octasaccharide derived by hydrolysis of type-III pneumococcal polysaccharide, but the corresponding 28-unit saccharide does cause detectable changes. The addition of 16-unit saccharide to anti-(SIII polysaccharide) IgG in the presence of Gd(III) does not change the solvent water proton relaxation rate, although aggregation does occur. The effects of the 28-unit saccharide may be explained therefore by a change in the tumbling time of the IgG. From a study of the effect of various antigen/antibody ratios, it is concluded that the 28-unit-saccharide-induced changes in the Gd(III) environment in the Fc region are caused by the specific geometrical structure of the antigen-antibody complexes formed, and not simply by occupancy of the combining sites on the antibody.

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

2021 ◽  
pp. 193229682110238
Author(s):  
Marc B. Taraban ◽  
Yilin Wang ◽  
Katharine T. Briggs ◽  
Yihua Bruce Yu
Keyword(s):  
Quality Control ◽  
Relaxation Rate ◽  
Drug Product ◽  
Proton Nmr ◽  
Water Proton ◽  
Proton Relaxation ◽  
Content Uniformity ◽  
Biologic Drugs ◽  
Insulin Solution ◽  
Insulin Pens

Background: There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product. Methods: Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R2(1H2O), a continuous numerical variable rather than binary pass/fail. Results: Ten pens of each product were inspected. R2(1H2O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R2(1H2O), presumably due to exposure to O2 in air. Conclusions: Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.

scholarly journals Survey of water proton longitudinal relaxation in liver in vivo

2021 ◽  
Author(s):  
John Charles Waterton
Keyword(s):  
Normal Liver ◽  
Population Variation ◽  
Water Proton ◽  
Proton Relaxation ◽  
Literature Searching ◽  
Repeatability Error ◽  
Coefficients Of Variation ◽  
Weighted Means ◽  
Propagation Of Errors

Abstract Objective To determine the variability, and preferred values, for normal liver longitudinal water proton relaxation rate R1 in the published literature. Methods Values of mean R1 and between-subject variance were obtained from literature searching. Weighted means were fitted to a heuristic and to a model. Results After exclusions, 116 publications (143 studies) remained, representing apparently normal liver in 3392 humans, 99 mice and 249 rats. Seventeen field strengths were included between 0.04 T and 9.4 T. Older studies tended to report higher between-subject coefficients of variation (CoV), but for studies published since 1992, the median between-subject CoV was 7.4%, and in half of those studies, measured R1 deviated from model by 8.0% or less. Discussion The within-study between-subject CoV incorporates repeatability error and true between-subject variation. Between-study variation also incorporates between-population variation, together with bias from interactions between methodology and physiology. While quantitative relaxometry ultimately requires validation with phantoms and analysis of propagation of errors, this survey allows investigators to compare their own R1 and variability values with the range of existing literature.

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