The Design And Bioactivity Of Mitochondria-targeting Luminescent Platinum Complex

Platinum-based antitcancer agents represent one of the great success in the field of medicinal inorganic chemistry,which has now become the most widely used cancer chemotherapy drugs.However the efficacy of traditional platinum drugs is badly limited by serious side toxicities and intrinsic or acquired drug resistance during the clinical therapy.A detailed understanding of the in vivo behavior of platinum drugs and their distribution is expected to provide a biological rationale for the design of new agents with imprvoed properties and fewer side effects.Overall celluar platinum atoms analysis and concentration following treatment with platinum complexes cam be measured using elemental spectroscopy techniques,inductively coupled plasma mass spectrometry(ICP-MS)and X-ray microanalysis.Apart from these techniques,tethering of fluorophores to platinum center and subsequent mapping of the localization of drug fluorescence in a relatively noninvasive procedure which can be performed on live cells.To achieve this aim,we designed three luminescent platinum complex.Chapter 2 mainly focus on two platinum complex based on Rhodamine B fluorescent moiety,binding to chelator group BPEA.Rhodamine B is extensively used in biotechnology appliction as of the excellent fluorescent property.These two platinum complex possess good optical property,favoring the desired cell imaging.These two platinum complex show the intensive DNA binding ability,which can be ascribed to the intercalation and electrostatic binding.CD spectra further proved that MRPt can induce B-to-Z DNA coonformatinal transition.These two platinum complex can be used as live cell imaging because of the low toxicity in high concentration.Confocal fluorescence imaging of CAOV-3 incubated with two complex disclosed that both could selectively accumulate in mitochondria instead of nucleus.This is a result of binding Rhodamine B moiety,which could impart a declocalized charge and lipophilic character to help accumulate in mitochondria.Chapter 3 showed the result from a novel luminescent platinum complex TPt with a metal carbon bond,which were rarely applied in antitumor activities.We used the N^C^N as chelating group to increase luminescent property,decorated with triphenylphosphonium(TPP)to improve selective accumulation in cells.Interaction with DNA and cellar distribution of this complex was investugated in this chapter.CD spectra showed strong ability of the complex to release DNA double helix.The cellular confocal fluorescence imaging showed that the complex prefer to accumulate in cell plasma instead of nucleus.