Complexes Having the fac-{M(CO)₃}⁺ Core (M = Tc, Re) Useful in Radiopharmaceuticals:  X-ray and NMR Structural Characterization and Density Functional Calculations of Species Containing Two sp³ N Donors and One sp³ O Donor

Abstract

Radiopharmaceuticals containing the "fac-[M(CO)3]+ " core (M=99mTc, 186Re, or 188Re) have potential as diagnostic or therapeutic agents. Complexes with this core with sp3 amine donors have received little attention. We have studied adducts formed by ENDACH2 (HO2CCH2NHCH2CH2NHCH2CO2H) and ENACH (NH2CH2CH2NHCH2CO2H). Re(CO)3(ENDACH)-A (1A) and Re(CO)3(ENDACH)-B (1B) isomers were obtained by the reaction of ENDACH2 with Re(CO)5Cl. Re(CO)3(ENAC) (2) was obtained by the reaction of ENACH with aqueous [Re(CO)3(H2O)3]+. From single-crystal X-ray data, the three new neutral complexes, 1A, 1B, and 2, have a six-coordinate, pseudo-octahedral Re center with facially coordinated carbonyl ligands. ENDACH- and ENAC- bind facially to Re through both amine nitrogens and one carboxyl oxygen, forming two five-membered chelate rings. The Re(CO)3(ENDACH) isomers have an uncoordinated, dangling -CH2CO2H group, which is an ideal coupling site for attachment to biomolecules. The isomers differ by the configuration of the NH center bearing this dangling group. The H atom of the amine (N2) is endo (near the carbonyl ligands in the basal plane) in 1A and exo (away from carbonyl ligands) in isomer 1B. Isomers reach equilibrium (1A:1B, 70:30) after 3 days at high pH. Density functional structure optimizations were performed for isolated molecules of the type Tc(I)/Re(I)(CO)3(N2O): [Re(CO)3(NH3)2(H2O)]+, [Tc(CO)3(NH3)2(H2O)]+, [Re(CO)3(EN)(H2O)]+ (EN, ethylenediamine), [Tc(CO)3(EN)(H2O)]+, and various models for 1A, 1B, and 2. The computed structures are in good agreement with the X-ray structures. The theoretical and experimental Re-N bond distances usually agree within 0.045 A. The total electronic energy values for the computed 1A and 1B models differ by 0.815 kcal mol(-1), giving an isomer ratio of 80:20, in good agreement with the 1A/1B ratio (70:30) found.

Iminoether Complexes of the Type, fac‐[Re(CO)3L{HNC(CH3)OCH3}]BF4 (L = Bipyridine or a Substituted Bipyridine): Synthesis and Properties

“…[1][2][3] This approach has led to the development of fac-{ 99m Tc(CO) 3 } + renal agents that have shown promising pharmacokinetic properties in humans. [4,5] We have noted that there are some problems in utilizing water, which is the solvent that is used to prepare the common precursor, fac-[Re(CO) 3 (H 2 O) 3 ] + .…”

“…[1] In water, the various pH conditions lead to different linkage isomers or mixtures of isomers for the complicated ligands. [2,3] In addition, it is inconvenient to monitor the formation of the complexes by NMR-spectroscopic methods under aqueous reaction conditions. Therefore, in order to overcome the above mentioned aqueous chemistry problems, we evaluated the use in the distortion of L and the methyl substituent position have little influence on the ease of iminoether formation.…”

Models for B12-Conjugated Radiopharmaceuticals. Cobaloxime Binding to Newfac-[Re(CO)3(Me2Bipyridine)(amidine)]BF4Complexes Having an Exposed Pyridyl Nitrogen

“…[Re(CO) 3 (6,6′-Me 2 bipy)(μ-(HNC(CH 3 )(pyppz)))Co(DH) 2 Cl]BF 4 (6). The use of the general method for the reaction of [Re(CO) 3 (6,6′-Me 2 bipy)(HNC(CH 3 )(pyppz))]BF 4 with (py)Co(DH) 2 Cl afforded 25 mg (78% yield) of yellow crystalline material.…”

Influence of the ligand donor atoms on the in vitro stability of rhenium(I) and technetium (I)-99m complexes with pyrazole-containing chelators: Experimental and DFT studies

“…DFT calculations on Tc and Re complexes potentially relevant in the radiopharmaceutical field, namely organometallic derivatives of fac-[M(CO) 3 ] + (M = Re, Tc), were recently reported [14][15][16]. Geerling et al investigated the influence of different combinations of N, O and S donor atoms ligands on the stability of Re(I)/Tc(I) tricarbonyl complexes, using simplified models of the real compounds [16].…”