Abstract
Quantum chemical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA, but Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the resulting structures show a large variation between the Y and In ions. A six-residue model of the active site containing metal ion-DOTA showed that the Y-DOTA structure optimized to a structure similar to the crystal structure but that the water molecule in In-DOTA disrupts the salt bridge between Arg98B and a carboxylate side chain of DOTA. These observed differences could in part explain the differential binding constants for Y-DOTA and In-DOTA to the antibody 2D12.5.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9225-9232 |
| Number of pages | 8 |
| Journal | Inorganic Chemistry |
| Volume | 45 |
| Issue number | 23 |
| DOIs | |
| State | Published - Nov 13 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Inorganic Chemistry
Cite this
Environmental effects on the structure of metal ion-DOTA complexes : An ab initio study of radiopharmaceutical metals. / Lau, Edmond Y; Lightstone, Felice C; Colvin, Michael E.
In: Inorganic Chemistry, Vol. 45, No. 23, 13.11.2006, p. 9225-9232.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Environmental effects on the structure of metal ion-DOTA complexes
T2 - An ab initio study of radiopharmaceutical metals
AU - Lau, Edmond Y
AU - Lightstone, Felice C
AU - Colvin, Michael E.
PY - 2006/11/13
Y1 - 2006/11/13
N2 - Quantum chemical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA, but Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the resulting structures show a large variation between the Y and In ions. A six-residue model of the active site containing metal ion-DOTA showed that the Y-DOTA structure optimized to a structure similar to the crystal structure but that the water molecule in In-DOTA disrupts the salt bridge between Arg98B and a carboxylate side chain of DOTA. These observed differences could in part explain the differential binding constants for Y-DOTA and In-DOTA to the antibody 2D12.5.
AB - Quantum chemical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA, but Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the resulting structures show a large variation between the Y and In ions. A six-residue model of the active site containing metal ion-DOTA showed that the Y-DOTA structure optimized to a structure similar to the crystal structure but that the water molecule in In-DOTA disrupts the salt bridge between Arg98B and a carboxylate side chain of DOTA. These observed differences could in part explain the differential binding constants for Y-DOTA and In-DOTA to the antibody 2D12.5.
UR - http://www.scopus.com/inward/record.url?scp=33751292004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751292004&partnerID=8YFLogxK
U2 - 10.1021/ic0602897
DO - 10.1021/ic0602897
M3 - Article
C2 - 17083220
AN - SCOPUS:33751292004
VL - 45
SP - 9225
EP - 9232
JO - Inorganic Chemistry
JF - Inorganic Chemistry
SN - 0020-1669
IS - 23
ER -