Metal Complexes as Antimicrobial Agents

malaria drugs

quinine and chloroquine

chloroquine

becomes concentrated in parasite food vacuoles and prevents polymerisation of heme into hemezoin - toxic

chloroquine resistance arises in Pf CRT (chloroquine channel) and prevents accumulation in the digestive vacuole

ferrocene in drugs

generally non-toxic and no bioactivity

replacing lipophilic moieties of drugs became popular as ferrocene can do redox reactions and maintains activity

ferroquine

2 generations of chloroquine analogues through replacing different segments with ferrous groups

ferrocene-chloroquine hybrids were most promising due to redox cycling

planar chirality - no difference in activity in enantiomers

long time to induce resistance and disappears quickly when exposure to drug stops

ferroquine mode of action

generation of ROS

interaction with hematin

B-hematin inhibition

accumulation and maintenance in food vacuole

alpha decay

emission of He²⁺ particle

shielded by latex gloves

beta- decay

conversion of neutron to proton

emission of an electron

shielded by glass/aluminium

beta+ decay

conversion of proton to neutron

emission of a positron

shielded by glass/aluminium

positron

antiparticle of electrons

used in positron emission tomography (PET)

if positron and electron meets, they annihilate and convert photons to energy

e⁺ + e^- → 2 photons

gamma radiation

emission of photons above 100keV

usually a side effect of decay mode