Article ID: 2015-0002
Some iron(III) complexes, including [Fe2(μ-O)(nta)2(H2O)2]2– (1), [Fe2(μ-O)(edda)2(H2O)2] (2), and [Fe2(μ-O)(ida)2(H2O)4] (3), are considered to be carcinogens causing renal injuries according to the results of previous animal experiments, where nitrilotriacetate [(nta)3–], ethylenediamine-N,N'-diacetate [(edda)2–], and iminodiacetate [(ida)2–] are the chelating ligands (chelators). On the other hand, a similar iron(III) complex [Fe2(μ-O)(pac)2(H2O)2] (4) is not considered to be a carcinogen, where N-(2-pyridylmethyl) iminodiacetate [(pac)2–] is the chelating ligand. In order to clarify the differences in carcinogenicity, the structures of complexes 1–4 were investigated based on the density functional theory (DFT) method, because the structures of complexes had not been clarified in solution. As a result, two-point interaction with hydrogen peroxide or α-helix was found to be possible for carcinogenic iron(III) complexes 1 and 3, whereas the interaction was found to be impossible for non-carcinogenic iron(III) complex 4.
Chemical structures of chelating ligands (chelators).
Structures of optimized isomers A1-A4.
Three isomers for an octahedral edda complex (trans, cis-α, and cis-β) and two conformational isomers for ethylene diamine moiety.
Structures of optimized isomers B1-B14.
Structures of optimized isomers C1-C12.
Structures of optimized isomers D1-D9.
Interaction of dinuclear iron(III) complexes with hydrogen peroxide. [Fe2(μ-O)(nta)2(μ-H2O2)]2– complex anions (A1-H2O2-1 and A1-H2O2-2) and [Fe2(μ-O)(ida)2(μ-H2O2)(H2O)2] complexes (C1-H2O2-1 and C1-H2O2-2).
Formation of [Fe2(μ-O)(edda)2(μ-H2O2)] (B1-H2O2) after a large deformation.
Interaction of dinuclear iron(III) complexes with tetraglycine (TG) in an α-helix form. [Fe2(μ-O)(nta)2(μ-TG)]2– complex anions (A1-helix and A1*-helix) and [Fe2(μ-O)(ida)2(μ-TG)(H2O)2] complexes (C1-helix and C1*-helix). Symbol * represents an inverted structure.
| No | Isomer | Point Group | Energydifference a |
| A1 | N5 (90,90) | C2 | 0.0 |
| A2 | N2 (180,90) | C2 | 11.4 |
| A3 | N3 (180,180) | C1 | 19.8 |
| A4 | N6 (90,180) | C2 | 39.3 |
a kcal mol–1.
| No | Isomer | Point Group | Energydifference a |
| B1 | cis-α,δδ,P,90° | C2 | 0.0 |
| B2 | cis-α,δδ,P,270° | C2 | 6.6 |
| B3 | cis-α,δλ,P,90° | C1 | 9.0 |
| B4 | cis-β,δδ,Q,90° | C2 | 12.6 |
| B5 | cis-β,δδ,P,270° | C2 | 14.7 |
| B6 | cis-β,δλ,P,180° | C1 | 22.4 |
| B7 | cis-β,δδ,Q,0° | C1 | 26.4 |
| B8 | cis-β,δλ,Q,0° | C1 | 29.1 |
| B9 | trans,δλ,Q | C1 | 32.8 |
| B10 | cis-β,δλ,Q,180° | C1 | 33.1 |
| B11 | cis-β,δδ,Q,270° | C2 | 34.6 |
| B12 | cis-β,δλ,Q,180° | C1 | 35.5 |
| B13 | trans,δδ,Q | C2 | 39.5 |
| B14 | cis-α,δλ,P,180° | Ci | 49.5 |
a kcal mol–1.
| No | Isomer | Point Group | Energydifference a |
| C1 | fac, 90°,sab, | C2 | 0.0 |
| C2 | mer, 180°, | C1 | 11.4 |
| C3 | mer, 90°,anc, | C2 | 11.4 |
| C4 | mer, 180°, | C2 | 11.8 |
| C5 | mer, 90°,syd, | C2 | 11.9 |
| C6 | fac, 90°,mie, | C1 | 12.5 |
| C7 | mer, 180°, | C1 | 15.7 |
| C8 | fac, 90°,mie, | C1 | 16.1 |
| C9 | fac, 180°, | C1 | 18.8 |
| C10 | fac, 90°,sab, | C2 | 19.6 |
| C11 | mer, 90°,syd, | C1 | 23.2 |
| C12 | fac, 90°,sab, | C2 | 25.8 |
a kcal mol–1.
b Two ligands have the same structure.
c Two ligands' amine hydrogen atoms are in anti positions.
d Two ligands' amine hydrogen atoms are in syn positions.
e Two ligands are in the mirror image.
| No | Isomer | Point Group | Energydifference a |
| D1 | mer(180,0,180) | C2 | 0.0 |
| D2 | fac(90,180,90),sab | C2 | 5.0 |
| D3 | mer(180,180,180) | Ci | 5.8 |
| D4 | mer(90,0,90) | C2 | 11.4 |
| D5 | fac(180,0,90),sab | C2 | 13.9 |
| D6 | fac(180,90,90),mic | Ci | 14.5 |
| D7 | fac(90,90,90),mic | C1 | 20.7 |
| D8 | fac(90,90,90),sab | C2 | 25.8 |
| D9 | fac(90,180,90),mic | Ci | 35.9 |
a kcal mol–1.
b Two ligands have the same structure.
c Two ligands are in the mirror image.
| No | Intact isomera | H2O2-adductb |
| A1 | 68.8° | 35.3° |
| B1 | 104.2° | 34.0° |
| C1 | 59.1° | 32.4° |
| D1 | 106.9° | ‒c |
a The O(water)-Fe···Fe-O(water) angle.
b The O(H2O2)-Fe···Fe-O(H2O2) angle for the most stable isomer.
c The structure was not obtained.
