10.1021/ic402737f.s001
Huiling Cui
Huiling
Cui
Richard Goddard
Richard
Goddard
Klaus-Richard Pörschke
Klaus-Richard
Pörschke
Alexandra Hamacher
Alexandra
Hamacher
Matthias
U. Kassack
Matthias
U.
Kassack
Bispidine Analogues of Cisplatin, Carboplatin, and
Oxaliplatin. Synthesis, Structures, and Cytotoxicity
American Chemical Society
2014
Complexes 1
2 b
hydrates 1 c
DMF
water yields
cancer cell lines K 562
Bispidine Analogues
parent analogues
Na 2C
platinum resistance factor
water networks
7H
2780 CisR
AgNO 3
complexes show
Dissolving 1 b
cytotoxic activity
2014-04-07 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Bispidine_Analogues_of_Cisplatin_Carboplatin_and_Oxaliplatin_Synthesis_Structures_and_Cytotoxicity/2308234
Bispidine (3,7-diazabicyclo[3.3.1]nonane,
C<sub>7</sub>H<sub>14</sub>N<sub>2</sub>) analogues of cisplatin,
carboplatin, and oxaliplatin
have been prepared. (C<sub>7</sub>H<sub>14</sub>N<sub>2</sub>)PtCl<sub>2</sub>·DMF (<b>1b</b>), obtained from (1,5-hexadiene)PtCl<sub>2</sub> and bispidine in DMF, is dimeric in the solid state. Dissolving <b>1b</b> in hot <i>N</i>-methylformamide allows crystallization
of the solvent-free polymeric (C<sub>7</sub>H<sub>14</sub>N<sub>2</sub>)PtCl<sub>2</sub> (<b>1a</b>). Recrystallization of <b>1a</b>,<b>b</b> from hot water yields the trihydrate (C<sub>7</sub>H<sub>14</sub>N<sub>2</sub>)PtCl<sub>2</sub>·3H<sub>2</sub>O
(<b>1c</b>). Reaction of <b>1</b> with Ag<sub>2</sub>(cbdca)
(cbdca = 1,1-cyclobutanedicarboxylate) in water affords the pentahydrate
(C<sub>7</sub>H<sub>14</sub>N<sub>2</sub>)Pt{C<sub>4</sub>H<sub>6</sub>(CO<sub>2</sub>)<sub>2</sub>}·5H<sub>2</sub>O (<b>2b</b>), which loses water in vacuo to give (C<sub>7</sub>H<sub>14</sub>N<sub>2</sub>)Pt{C<sub>4</sub>H<sub>6</sub>(CO<sub>2</sub>)<sub>2</sub>} (<b>2a</b>). Reaction of <b>1</b> with AgNO<sub>3</sub> in water, followed by addition of Na<sub>2</sub>C<sub>2</sub>O<sub>4</sub>, affords the water-free polymeric (C<sub>7</sub>H<sub>14</sub>N<sub>2</sub>)Pt(C<sub>2</sub>O<sub>4</sub>) (<b>3</b>). All
complexes have been structurally characterized, revealing various
patterns of N–H···Cl and N–H···O
hydrogen bonds. In the hydrates <b>1c</b> and <b>2b</b> the complexes are embedded in intricate three-dimensional water
networks. Complexes <b>1a</b>, <b>2a</b>, and <b>3</b> have been tested for their cytotoxicity against human cancer cell
lines K562 (chronic myeloid leukemia), A2780 (ovarian cancer), and
its platinum-resistant subline A2780 CisR and are compared to their
parent analogues. The new complexes show significant cytotoxic activity
along with a low platinum resistance factor.