Computational approaches to the study of some lanthanide (III)-polyazamacrocyclic chelates for magnetic resonance imaging

Abstract

A set of parameters consistent with the CHARMM force field has been Ž . determined for molecular dynamics simulations of several DOTA᎐ and DOTP᎐Ln III chelates. Bonding and van der Waals parameters were derived from the available experimental data and analogy to similar ones in the existing force field. Net atomic charges were derived from ab initio calculations at the Hartree᎐Fock level to reproduce Ž . Ž . molecular electrostatic potentials ESPs , with an effective core potential ECP basis set for the metal ion and the 6-31G U basis set for the ligand atoms. The charges are consistent with the TIP3P water model. Preliminary molecular dynamics simulations of the lanthanide chelates in aqueous solution were performed using the Nose᎐Hoover thermostat at 300 K. The new parameters correctly predicted the molecular structures and stability of the chelates major and minor isomers.

Studies of inclusion complexes between cyclodextrins and polyazamacrocyclic chelates of lanthanide (III) ions

“…Notice that the guest structures are almost nonflexible (refer to the corresponding relatively small RMS values in table 3), as predicted by Henriques et al [23]. Consequently, the distances between the cyclodextrin hydroxyl groups and the chelate charged oxygens vary significantly under dynamic conditions, and that should account for most of the electrostatic energy fluctuations.…”

“…These particular structures, m 0 and M 0 , are meant to be analogous to the above referred m and M isomers respectively, but without the capping water molecule. Therefore, the [Tm(DOTP)] 5À m 0 structure was modelled [23], after the crystal structures of the complexes with the DOTP-like tetraalkyl-phosphinate ligands [22], DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenemethylphosphinate) and DOTBzP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenebenzylphosphinate), by substituting the four R groups (R Bz, Me) by the phosphonate oxygens in DOTP. The M 0 isomer was built based on the NMR structural results [8].…”

“…All terms followed a heuristic fitting until the CHARMM simulated structures were in good agreement with the experimental ones. Details of the parameterisation have been reported elsewhere [23,28].…”

How Can Fluctional Chiral Lanthanide (III) Complexes Achieve a High Stereoselectivity in Aqueous Mukaiyama-Aldol Reaction?

“…22−24 Complexes of related DOTAs (1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid) derivatives with Ln 3+ , although never applied as catalysts, have been widely used for in vivo luminescent probes 25−27 and MRI contrast agents, 28−35 and their structures and chemical properties have been studied both experimentally 28−35 and theoretically. 36,37 According to these studies, achiral Ln 3+ -DOTA has four stereoisomers, two pairs of enantiomers (as shown in Figure S1 in Supporting Information (SI)), and the existing probability of each conformer depends on Ln 3+ . Additionally, their chemical properties, such as the rate of water exchange on Ln 3+ , depend on the stereoisomers.…”

“…Catalytic reactions in aqueous media have recently been one of the most important topics for green chemistry. − Although conventional Lewis acid catalysts are inactive in water, a number of water-tolerant Lewis acid catalysts have been reported. − Lanthanide (Ln) complexes fit into this group of catalysts. Ln trication (Ln 3+ ) catalysts were in fact used in the first report of aqueous C–C bond formation, the so-called Kobayashi modification of Mukaiyama-Aldol reaction, , and have been used in many aqueous reactions. − Stereoselective reactions in aqueous media have also been reported with chiral ligands that are quite different from those widely used under anhydrous conditions. − One of the distinct chiral ligands is crown ether derivatives. − Allen and co-workers used the chiral complex of fluctional C 2 symmetric (2 R ,2′ R )-dialkyl 2,2′-(1,7-dioxa-4,10-diazacyclo­dodecane-4,10-diyl)­dipropanoates, abbreviated here as DODPs, and achieved highly enantio- and diastereoselective aqueous Mukaiyama-Aldol reaction between benzaldehyde and silyl enol ether, as shown in Scheme . − Complexes of related DOTAs (1,4,7,10-tetraazacyclo­dodecane- N , N ′, N ″, N ‴-tetraacetic acid) derivatives with Ln 3+ , although never applied as catalysts, have been widely used for in vivo luminescent probes − and MRI contrast agents, − and their structures and chemical properties have been studied both experimentally − and theoretically. , According to these studies, achiral Ln 3+ -DOTA has four stereoisomers, two pairs of enantiomers (as shown in Figure S1 in Supporting Information (SI)), and the existing probability of each conformer depends on Ln 3+ . Additionally, their chemical properties, such as the rate of water exchange on Ln 3+ , depend on the stereoisomers.…”