Rhenium and Technetium mixed ligand complexes with Ciprofloxacin derivatives and Phosphines

Postgraduate Thesis uoadl:2059246 817 Read counter

Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - Ραδιοφαρμακευτική Χημεία
Library of the School of Science
Deposit date:
2017-10-20
Year:
2017
Author:
Papadopoulou Eleni
Supervisors info:
Ανδρέας Τσοτίνης, Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Παναγιώτης Μαράκος, Καθηγητής,Τμήμα Φαρμακευτικής, ΕΚΠΑ
Ιωάννης Πιρμεττής, Ερευνητής Α', ΙΠΡΕΤΕΑ, ΕΚΕΦΕ Δημόκριτος
Original Title:
Μικτά Σύμπλοκα του Ρηνίου και του Τεχνητίου με παράγωγα της Σιπροφλοξασίνης και Φωσφίνες.
Languages:
Greek
Translated title:
Rhenium and Technetium mixed ligand complexes with Ciprofloxacin derivatives and Phosphines
Summary:
Aiming at the development of infection imaging agents, a series of new 99mTc tricarbonyl [2+1] mixed ligand complexes with ciprofloxacin dithiocarbamate as bidentate ligand (CipCS2) and various phosphines as monodentate ligands (P) were synthesized and characterized.
Ciprofloxacin reacted with carbon disulphide to give ligand CipCS2Na2. Reaction of equimolar quantities of CipCS2Na2 with the precursor [NEt4]2[ReBr3(CO)3] afforded Re(CO)3(CipCS2)(H2O), 1. Addition of triphenylphosphine (PPh3) to a solution of 1 afforded the mixed ligand complex Re(CO)3(CipCS2)(PPh3), 4, by substitution of the water molecule. In an alternative one-pot way, simultaneous addition of the bidentate ligand CipCS2Na2 and the monodentate ligands dimethylphenylphosphine (DMPP), methyl(diphenyl)phosphine (MPPh2), triphenylphosphine (PPh3), tris(4-methoxyphenyl) phosphine (TMPP), and 1,3,5-Triaza-7-phosphaadamantane (ADAP) to a solution of ReCO5Br afforded the mixed ligand complexes 2 - 6 of the general formula Re(CO)3(CipCS2)(P). The rhenium complexes 1-6 were characterized by IR and NMR spectroscopies. Rhenium complexes 2-6 were prepared in higher overall yield with the one-pot synthesis.
At technetium-99m level, reaction of CipCS2Na2 with the precursor fac-[99mTc(OH2)3(CO)3]+ at 70oC for 30 min resulted in the formation of fac-[99mTc(CO)3(CipCS2)(H2O)], 1’. Addition of phosphines to 1’ resulted in the quantitative formation of complexes fac-[99mTc(CO)3(CipCS2)(P)], 2’-6’. The technetium complexes 2’-6’ were characterized by comparative HPLC studies using the Re analogues as standards.
Stability studies showed that the 99mTc complexes are stable in their reaction mixture and after isolation by HPLC for at least 24 hours. Challenge experiments with histidine and cysteine for complexes 2’-6’showed high stability up to 6 hr.
Biodistribution studies have shown that complexes 1’-6’ had no significant uptake in stomach 2 hrs p.i., indicating their in vivo stability. All complexes showed high uptake in the liver and low radioactivity in the urine. All compounds showed high selective uptake in the infected tissue except for complex 6’. Complex 4’ showed at 15 and 120 min p.i. higher radioactivity uptake in the infected muscle (2.93±0.09 and 3.12±0.14) compared to the uptake in the normal muscle and the aseptic inflammation. Complex 5’, at 120 min p.i, showed a promising infected/normal muscle ratio of 3.32, while inflammation/ normal muscle ratio was 1.51.
In conclusion, these encouraging results make both complexes candidate agents for the differential diagnosis of infection and further studies will be conducted to prove the possible use of these complexes as infection imaging agents.
Main subject category:
Science
Other subject categories:
Pharmacy
Keywords:
Rhenium, Technetium, Ciprofloxacin, Infection, Imaging
Index:
Yes
Number of index pages:
2
Contains images:
Yes
Number of references:
129
Number of pages:
100
File:
File access is restricted only to the intranet of UoA.

MASTER ΠΑΠΑΔΟΠΟΥΛΟΥ ΕΛΕΝΗ.pdf
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