Angelo Amoroso Flashcards
Four Synthetic Protocols to synthesis SPIONs
- Co-precipitation
- Constrained Environment
- Hydrothermal High temp
- Sonolysis
Why are SPIONs typically coated?
- Stabilisation, prevents particles from aggregation in biological conditions. In iron oxide the surface iron acts as a Lewis acid and co-ordinates ligands. The replacement of surface OH groups is pH dependent.
- Functionality, add groups for different biological applications
How can SPIONs be functionalised to allow conjugation?
Coat the nanoparticles with silica. An R group on the Silica can contain a functional group (e.g NH2) from which we can link to the surface.
Positive Contrast Imaging
A positive contrast agent is a species that causes a significant change in the T1 relaxation time
Negative contrast Imaging
A negative contrast agent is a species that causes a significant change in the T2 relaxation time
Example of a positive and negative contrast agent.
With both species indicate what makes them good contrast agents
Positive - Gd(III) comple - Gd-DOTA
- High spin F7 configuration
- Large magnetic moment
- Symmetrical spin states
- electron relaxation (Gd) needs to be a similar relaxation to the nuclei
Negative - SPIONs - Fe3O4
- Highly paramagnetic material
- disturb the field homogeneity causing rapid dephasing of the bulk
How do water exchange rates affect r1 relaxivity?
- exchange rate is 1/lifetime in inner sphere
- The exchange rate is proportional to relaxivity so increase the exchange rate increase r1 (more water molecules relaxed)
- However there if the exchange rate is too high then r1 can start to decrease (Not enough time spent on complex to relax)
Explain why increase in relaxivity is expected but often not observed?
- Generally as we increase the size of the molecule (MWt), the tumbling decreases, which increases relaxivity.
- However this is not always observed as tumbling is dependent on internal flexibility (dependent on segmental motion)
Features that must be present for in-vivo application
- Non toxic
- Functional contrast agent
- Significant change in T1 and T2 values
Name MRI stimulus’ in biological environments
- pH responsive
- Enzyme responsive
Name MRI stimulus’ in biological environments and how they could function
pH responsive
- A change in pH could increase tumbling time as molecules could shrink (long chain polymers)
- A change in pH could alter q (displace water)
Enzyme responsive
-In the presence of an enzyme, make space for water molecules to coordinate (chopping of moiety). Change q
Key parameters that affect relaxivity
- q number
- optimising water exchange rates
- tumbling rate
How do sterics effect water exchange?
- Only affected by sterics of the inner sphere!
- Replacing carboxylate for an amide decrease exchange rate by 3-4 times
- The carboxylate is more crowded i.e the coordination of the O- is shorter and favours dissociation of water (water squeezed out)
How do Charge effect water exchange?
A higher negative charge favours the leaving of the water molecule
How does the number of water molecules affect water exchange?
More water molecules = less stereo-rigidity
therefore increasing water exchange
Alternative the Gd(III) complexes
Mn(II)
Relaxivity is poorer but less toxic
Can trap in liposomes to decrease toxicity and have high relaxivity
Describe a pulse sequence that will result in a T1-weighted image.
Draw a pulse sequence showing TR, TE, 90degree pulse, 180degree pulse and spin echo.
For a T1 weighted image you would need a short TR time and a short TE time. This will maximise contrast for T1.
short TE negates any differences in T2.
The required TR & TE for a T1 weighted exp, T2 weighted exp and proton density contrast
-T1 weighted exp: TR short TE short -T2 weighted exp: TR long TE long -Proton Density TR long TE short
Sequence for a proton weighted image?
- Allow all protons to count the same, allow all to relax back up (long TR)
- No significant difference in de-phasing (short TE)
- Every proton is the same, can integrate for proton density
Co-precipitaion
- Simplest method
- Size and shape may be tailored by adjusting pH, ionic strength, temperature, counter-ion, rate of addition, rate of stirring.
- Wide range of particle diameter
- Add citrate to control diameter to 3nm (coating of citrate inhibits growth)
Constrained environment
-Use of surfactants to create water swollen reverse micellular structures in non-polar solvents in which NP can form
Hydrothermal/High Temp
Nanoparticles with a high level of mono-disperity and size control can be prepared by the high temperature decomposition of iron organic precursors. (Fe(CO)5 or Fe(acac)3)
Sonolysis
shape and size of the nanoparticles can be adjusted by varying the operating parameters which
include ultrasonic power, current density, deposition potential and the ultrasonic vs
electrochemical pulse times.
r(obs) equation ?
r(obs) = 1/T(dia) + (r(i) x [Gd])
r(i) = 1/T1
