Introduction and some general principles Flashcards
What are the advantages of metal complexes over purely organic molecules?
Variable oxidation state of metal, potential for unique photochemical and redox reactivity, exchangeable ligands for coordination, dual agents with metal and ligand having different functions, higher control of 3D geometry and structure
Why is crystal field theory important in this context?
Can use crystal field theory to make predictions about metal complex behaviour
Why are rates of ligand exchange important in this context?
Determine metal’s ability to coordinate to other species (too fast and won’t make it to the target, too slow and won’t have therapeutic effects)
How do metal complexes target DNA?
Coordination of metal centre to nucleobase (e.g. N7 on guanine) or by intercalation. DNA replication impacted, apoptosis follows.
How do metal complexes target enzymes?
Block incoming substrates to active site by coordination, exchange active metal to inactive metal in metalloenzymes, inert complex blocks active site
Why is the production of ROS important?
Generally controlled process in cells. Can come under oxidative stress with metal complex, causing uncontrolled generation of ROSs which damage cell components, leading to apoptosis or denaturing of enzymes by reaction with radical species.
How is a cytotoxicity assay performed?
96 well plate with cells in bottom. Have a positive and a negative control of dead and completely live cells. Varying concentrations of drug added with triplicate repeats of each. Cell viability then tested.
What important information is gleaned from a cytotoxicity assay?
Dose response curve generated can be used to calculate IC50 etc. values.
How can cell viability be tested? Key: MTT assay
MTT assay…solution of MTT is added to all wells. Viable cells will metabolise to purple solution from clear…measure absorbance and plot absorbance vs drug concentration to produce a drug-response curve.
What is the difference between apoptosis and necrosis?
Apoptosis is programmed cellular death due to failure - this is controlled by the cell. Necrosis is cell death due to uncontrolled reasons.
