Synthesis, characterization, and binding properties towards CT-DNA and lipoxygenase of mixed-ligand silver(I) complexes with 2-mercaptothiazole and its derivatives and triphenylphosphine

• Published in: Journal of biological inorganic chemistry Vol. 19; no. 3; pp. 449 - 464
• Main Authors: Kyros, L., Banti, C. N., Kourkoumelis, N., Kubicki, M., Sainis, I., Hadjikakou, S. K.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2014
• Subjects: Animals; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Benzothiazoles - metabolism; Biochemistry; Biomedical and Life Sciences; Cattle; Crystallography, X-Ray; DNA - chemistry; DNA - metabolism; Escherichia coli; Life Sciences; Lipoxygenase - chemistry; Lipoxygenase - metabolism; Microbiology; Organophosphorus Compounds - chemical synthesis; Organophosphorus Compounds - chemistry; Organophosphorus Compounds - metabolism; Original Paper; Protein Binding - physiology; Pseudomonas aeruginosa; Silver - chemistry; Silver - metabolism; Spectrophotometry, Ultraviolet; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - metabolism; Antibacterial activity; Bioinorganic chemistry; Silver(I) chloride complexes; Heterocyclic thioamides; DNA binding
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-014-1089-6

Mixed-ligand silver(I) complexes of formulae [AgCl(TPP)
2
(MTZD)] (
1
), {[AgCl(TPP)
2
(MBZT)]·(MBZT)·2(toluene)} (
2
), and [AgCl(TPP)
2
(CMBZT)] (
3
) were obtained by refluxing toluene solutions of silver(I) chloride with triphenylphosphine (TPP) and the appropriate heterocyclic thioamides 2-mercaptothiazolidine (MTZD), 2-mercaptobenzothiazole (MBZT), and 5-chloro-2-mercaptobenzothiazole (CMBZT). The complexes were characterized by the melting point, vibrational spectroscopy (Fourier transform mid-IR),
1
H-NMR spectroscopy, UV–vis spectroscopy, and X-ray crystallography. DNA binding tests indicate the ability of complexes
1
–
3
to modify the activity of cells. The binding constants of
1
–
3
towards calf-thymus DNA (CT-DNA) [(3.5 ± 8.5) × 10
4
 M
−1
for
1
, (10.0 ± 0.0) × 10
4
 M
−1
for
2
, and (46.4 ± 7.0) × 10
4
 M
−1
for
3
] indicate strong interaction of
3
. Changes in the fluorescence of ethidium bromide in the presence of DNA suggest intercalation into or electrostatic interactions with DNA. The corresponding apparent binding constants (
K
app
) towards CT-DNA calculated through fluorescence spectra are (3.5 ± 0.7) × 10
4
 M
−1
for
1
, (10.0 ± 0.0) × 10
4
 M
−1
for
2
, and (46.4 ± 7.0) × 10
4
 M
−1
for
3
. Docking studies on DNA complexes confirm the binding of
1
and
2
in the major groove of CT-DNA and of
3
in the minor groove. Moreover, the influence of
1
–
3
on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase was studied kinetically and theoretically. The antibacterial effect of
1
–
3
against the bacterial species
Pseudomonas aeruginosa
and
Escherichia coli
was evaluated. Complex
1
exhibits the strongest activity.
Graphical abstract
The silver(I) chloride complexes [AgCl(TPP)
2
(MTZD)] (
1
), {[AgCl(TPP)
2
(MBZT)]·(MBZT)·2(toluene)} (
2
), and [AgCl(TPP)
2
(CMBZT)] (
3
), where TPP is triphenylphosphine, MTZD is 2-mercaptothiazolidine, MBZT is 2-mercaptobenzothiazole, and CMBZT is 5-chloro-2-mercaptobenzothiazole, were structurally characterized. The binding affinity of
1
–
3
towards the intracellular molecules calf-thymus DNA and lipoxygenase were studied to determine the ability of complexes
1
–
3
to modify the activity of cells.