Edward C. Lisic

Synthesis of a new bisphosphonic acid ligand (SEDP) and preparation of a 188Re-(Sn)SEDP bone seeking radiotracer

The new bisphosphonate ligand SEDP (2-sulfonato-1,1-ethylidene bisphosphonic acid) has been synthesized and characterized, including the determination of the protonation constants, and used to form (188)Re-(Sn)SEDP from Na(188)ReO4. The title compound (188)Re-(Sn)SEDP shows slightly greater bone uptake and less kidney uptake than (188)Re-(Sn)HEDP in rat biodistribution studies.

99mTc(L-L)3+ complexes containing ether analogs of DMPE

Novel 99mTc(L-L)3+ complexes have been investigated for potential use in myocardial perfusion imaging. Bidentate chelators have been prepared that are based on substituent analogs of 1,2-bis(dimethylphosphino)ethane, onto which alkyl ether groups have been incorporated. The new ligands are: (1) MMPE, 1,2-bis(methyl methoxyethyl phosphino)ethane, (2) MIBPE, 1,2-bis(methyl methoxyisobutyl phosphino)ethane, (3) FURPE, 1,2-bis(methyl tetrahydrofuran phosphino)ethane, and (4) PYRPE, 1,2-bis(methyl tetrahydropyran phosphino)ethane. These ligands have been reacted with 99mTc and the resulting complexes evaluated for myocardial imaging properties. 99mTc(MMPE)3+ exhibited the most favorable myocardial imaging characteristics in animal models. Results indicate that pendent ether moieties can improve the myocardial imaging properties of cationic technetium complexes.

Examination of the Impact of Copper(II) α-(N)-Heterocyclic Thiosemicarbazone Complexes on DNA Topoisomerase IIα

Type II DNA topoisomerases resolve topological knots and tangles in DNA that result from routine cellular processes and are effective targets for anticancer therapeutics. To this end, thiosemicarbazones have been identified as having the ability to kill cancer cells from several cell lines. Literature evidence suggests that at least some thiosemicarbazones have an impact on topoisomerase II activity. However, the mechanism is not as clearly defined. Therefore, we set out to analyze the activity of four α-(N)-heterocyclic thiosemicarbazone compounds against topoisomerase IIα. The ligands, acetylpyridine-ethylthiosemicarbazone (APY-ETSC) and acetylpyrazine-methylthiosemicarbazone (APZ-MTSC), and their copper(II) [Cu(II)] complexes [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl] were examined for the ability to impact the catalytic cycle of human topoisomerase IIα. Both [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl] were more effective at inhibiting DNA relaxation compared with the ligands alone. Further, both [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl] increased double-stranded DNA cleavage levels without inhibiting topoisomerase IIα-mediated DNA ligation. The Cu(II) complexes inactivate enzyme activity over time suggesting a critical interaction with the enzyme. Additionally, we found that the Cu(II)-thiosemicarbazone complexes do not significantly impact DNA cleavage by the catalytic core of the enzyme. This evidence is supported by the fact that both [Cu(APY-ETSC)Cl] and [Cu(APZ-MTSC)Cl], and to a lesser extent the ligands, inhibit topoisomerase IIα-mediated ATP hydrolysis. Based upon kinetic analysis, the Cu(II) complexes appear to be noncompetitive inhibitors of the ATPase domain of topoisomerase IIα. Taken together, our results provide evidence that Cu(II) complexes of α-(N)-heterocyclic thiosemicarbazones catalytically inhibit the enzyme through the ATPase domain but also promote double-stranded DNA cleavage by the enzyme.

Hybrid density functional theory investigation of a series of alloxan-based thiosemicarbazones and semicarbazones

Recently, the synthesis and the NMR characterization of a series of eight alloxan-based thiosemicarbazones and semicarbazones were reported. These compounds exhibit a strongly hydrogenbonded hydrazinic proton that is a part of a characteristic six-membered ring. This proton is highly deshielded and resonates far downfield in the proton NMR spectra. In this report, mPW1PW91/6-31+G(d,p) calculations have been used to investigate the structure and other molecular properties of this series of eight compounds. The relationship between the 1H and 13C NMR chemical shifts and various geometric parameters was investigated, and linear relationships for proton peaks that are involved in hydrogen-bond interactions were found.

Potential Heavy Metal Water Remediation Using 5-Formylfuran-2-Sulfonic Acid Thiosemicarbazone Chelating Resins

Strong anion exchange resins were separately loaded with three new 5-formylfuran-2-sulfonic acid thiosemicarbazone ligands and tested to determine if they could be utilized for heavy-metal water remediation. The ligands were tested for microbial activity using MIC tests, and were found to be inactive even at high concentrations. Resins used in the study were loaded with one percent by weight of each ligand, and then were exposed to Co-57, Ni-63, or Cd-109, using batch techniques at various environmental pH levels at different time intervals. The adsorption values of the metals to the resin beads were calculated as dry-weight distribution (Dw) values.