Tuning the reactivity in classic low-spin d6 rhenium(I) tricarbonyl radiopharmaceutical synthon by selective bidentate ligand variation (L,L'-Bid; L,L'= N,N', N,O, and O,O' donor atom sets) in fac-[Re(CO)3(L,L'-Bid)(MeOH)]n complexes

A range of fac-[Re(CO)(3)(L,L'-Bid)(H(2)O)](n) (L,L'-Bid = neutral or monoanionic bidentate ligands with varied L,L' donor atoms, N,N', N,O, or O,O': 1,10-phenanthroline, 2,2'-bipydine, 2-picolinate, 2-quinolinate, 2,4-dipicolinate, 2,4-diquinolinate, tribromotropolonate, and hydroxyflavonate; n = 0, +1) has been synthesized and the aqua/methanol substitution has been investigated. The complexes were characterized by UV-vis, IR and NMR spectroscopy and X-ray crystallographic studies of the compounds fac-[Re(CO)(3)(Phen)(H(2)O)]NO(3)·0.5Phen, fac-[Re(CO)(3)(2,4-dQuinH)(H(2)O)]·H(2)O, fac-[Re(CO)(3)(2,4-dQuinH)Py]Py, and fac-[Re(CO)(3)(Flav)(CH(3)OH)]·CH(3)OH are reported. A four order-of-magnitude of activation for the methanol substitution is induced as manifested by the second order rate constants with (N,N'-Bid) < (N,O-Bid) < (O,O'-Bid). Forward and reverse rate and stability constants from slow and stopped-flow UV/vis measurements (k(1), M(-1) s(-1); k(-1), s(-1); K(1), M(-1)) for bromide anions as entering nucleophile are as follows: fac-[Re(CO)(3)(Phen)(MeOH)](+) (50 ± 3) × 10(-3), (5.9 ± 0.3) × 10(-4), 84 ± 7; fac-[Re(CO)(3)(2,4-dPicoH)(MeOH)] (15.7 ± 0.2) × 10(-3), (6.3 ± 0.8) × 10(-4), 25 ± 3; fac-[Re(CO)(3)(TropBr(3))(MeOH)] (7.06 ± 0.04) × 10(-2), (4 ± 1) × 10(-3), 18 ± 4; fac-[Re(CO)(3)(Flav)(MeOH)] 7.2 ± 0.3, 3.17 ± 0.09, 2.5 ± 2. Activation parameters (ΔH(k1)(++), kJmol(-1); ΔS(k1)(), J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as indicated are as follows: fac-[Re(CO)(3)(Phen)(MeOH)](+) iodide 70 ± 1, -35 ± 3; fac-[Re(CO)(3)(2,4-dPico)(MeOH)] bromide 80.8 ± 6, -8 ± 2; fac-[Re(CO)(3)(Flav)(MeOH)] bromide 52 ± 5, -52 ± 15. A dissociative interchange mechanism is proposed.     

fac-[Re(CO)(3)L](+) complexes with N-CH(2)-CH(2)-X-CH(2)-CH(2)-N tridentate ligands. synthetic, X-ray crystallographic, and NMR spectroscopic investigations

Polyamine ligands (L) have excellent binding characteristics for the formation of fac-99mTc(CO)3-based radiopharmaceuticals. Normally, these L are elaborated so as to leave pendant groups designed to impart useful biodistribution characteristics to the fac-[99mTc(CO)3L] imaging agent. Our goal is to lay a foundation for understanding the features of the bound elaborated ligands by using the fac-[Re(CO)3L]-analogue approach with the minimal prototypical ligands, diethylenetriamine (dien) or simple dien-related derivatives. Treatment of the fac-[Re(CO)3(H2O)3]+ cation with such triamine (NNN) ligands afforded fac-[Re(CO)3L]+ complexes. Ligand variations included having a central amine thioether donor, thus allowing X-ray crystallographic and NMR spectroscopic comparisons of fac-[Re(CO)3L]+ complexes with NNN and NSN ligands. fac-[Re(CO)3L]+ complexes with two terminal exo-NH groups exhibit unusually far upfield exo-NH NMR signals in DMSO-d6. Upon the addition of Cl-, these exo-NH signals move downfield, while the signals of any endo-NH or central NH groups move very little. This behavior is attributed to the formation of 1:1 ion pairs having selective Cl- hydrogen bonding to both exo-NH groups. Base addition to a DMSO-d6 solution of meso-exo-[Re(CO)3(N,N',N'-Me3dien)]PF6 led to isomerization of only one NHMe group, producing the chiral isomer. The meso isomer did not form. The [Re(CO)3(N,N,N',N',N'-pentamethyldiethylenetriamine)]triflate.[Re(CO)3(mu3-OH)]4.3.35H2O crystal, the first structure with a fac-[Re(CO)3L] complex cocrystallized with this well-known cluster, provided parameters for a bulky NNN ligand and also reveals CO-CO interlocking intermolecular interactions that could stabilize the crystal.     

Developing the {M(CO)3}+ core for fluorescence applications: Rhenium tricarbonyl core complexes with benzimidazole, quinoline, and tryptophan derivatives

Tridentate ligands derived from benzimidazole, quinoline, and tryptophan have been synthesized, and their reactions with [NEt4]2[Re(CO)3Br3] have been investigated. The complexes 1-4 and 6 and 7 exhibit fac-{Re(CO)3N3} coordination geometry in the cationic molecular units, while 5 exhibits fac-{Re(CO)3N2O} coordination for the neutral molecular unit, where N3 and N2O refer to the ligand donor groups. The ligands bis(1-methyl-1H-benzoimidazol-2-ylmethyl)amine (L1), [bis(1-methyl-1H-benzoimidazol-2-ylmethyl)amino]acetic acid ethyl ester (L2), [bis(1-methyl-1H-benzoimidazol-2-ylmethy)amino]acetic acid methyl ester (L3), [bis(quinolin-2-ylmethyl)amino]acetic acid methyl ester (L4), 3-(1-methyl-1H-indol-3-yl)-2-[(pyridin-2-ylmethyl)amino]propionic acid (L5), 2-[bis(pyridin-2-ylmethyl)amino]-3-(1-methyl-1H-indol-3-yl)propionic acid (L6), and 2-[bis(quinolin-2-ylmethyl)amino]-3-(1-methyl-1H-indol-3-yl)propionic acid (L7) were obtained in good yields and characterized by elemental analysis, 1D and 2D NMR, and high-resolution mass spectrometry (HRMS). The rhenium complexes were obtained in 70-85% yields and characterized by elemental analysis, 1D and 2D NMR, HRMS, IR, UV, and luminescence spectroscopy, as well as X-ray crystallography for [Re(CO)3(L1)]Br (1), {[Re(CO)3(L2)]Br}2.NEt4Br . 8.5H2O (3(2).NEt4Br . 8.5H2O), [Re(CO)3(L4)]Br (4), and [Re(CO)3(L6)]Br (6). Crystal data for C21H19BrN5O3Re (1): monoclinic, P2(1)/c, a = 13.1851(5) A, b = 16.1292(7) A, c = 10.2689(4) A, beta = 99.353(1) degrees , V = 2154.8(2) A3, Z = 4. Crystal data for C56H73Br3N11O18.50 Re2 (3(2).NEt4Br . 8.5H2O): monoclinic, C2/c, a = 34.7760(19) A, b = 21.1711(12) A, c = 20.3376(11) A, beta = 115.944(1) degrees , V = 13464.5(1) A3, Z = 8. Crystal data for C26H21BrN3O5Re (4): monoclinic, P2(1)/c, a = 16.6504(6) A, b = 10.1564(4) A, c = 14.6954(5) A, beta = 96.739(1) degrees , V = 2467.9(2) A3, Z = 4. Crystal data for C27H24BrN4O5Re (6): monoclinic, P2(1), a = 8.7791(9) A, b = 16.312(2) A, c = 8.9231(9) A, beta = 90.030(1) degrees , V = 1277.8(2) A3, Z = 2.     

Binding interaction of [Re(H2O)3(CO)3]+ with the DNA fragment d(CpGpG)

Insights into the interaction of the [Re(H2O)3(CO)3]+ complex (1) with the DNA fragment d(CpGpG) have been obtained by one- (1D) and two-dimensional (2D) NMR spectroscopy. The H8 resonances of the single major [Re(H2O)d(CpGpG)(CO)3]- adduct (2) exhibit pH-independent chemical shift changes attributable to metal N7 binding. The structure of this adduct has been characterized by molecular modeling studies based on 1D and 2D NMR data. In solution, 2 shows the presence of two N7-coordinated guanine moieties in a head-to-head (HH) orientation as evidenced by G2H8/G3H8 cross-peaks in the 1H-1H NOESY NMR spectrum. The presence of the 5'-bridging phosphodiester appears to stabilize the HH1 L conformer, as was previously described for related Pt and Rh complexes.     

fac-[Re(CO)3(H2O)3]+ nucleoside monophosphate adducts investigated in aqueous solution by multinuclear NMR spectroscopy

The fac-[Re(CO)3(H2O)3]+ cation, the putative DNA-binding species accounting for the biological activity of related Re(I) complexes, binds reversibly to N7 of 6-oxopurine nucleotide monophosphates (NMPs), in contrast to Pt(II) anticancer drugs. A relatively high amount of NMP is needed to convert all of the fac-[Re(CO)3(H2O)3]+ to adducts. The Re/nucleotide 1:1 adduct forms more rapidly and builds up to a higher concentration for guanosine 5'-monophosphate (5'-GMP) and inosine 5'-monophosphate (5'-IMP) than for the respective 3'-monophosphates (3'-GMP and 3'-IMP). These results are attributable to the 5'-positioning of the 5'-NMP phosphate group that allows it to approach the metal inner sphere for more favorable cation electrostatic and aqua ligand H-bonding interactions, both in the initial productive ion pair encounter complexes and in the N7-bound 1:1 adducts. A higher reactivity of 5'-GMP over 3'-GMP is known for cisplatin. In contrast, more Re/nucleotide 1:2 adduct was formed by 3'-GMP (and 3'-IMP) than by 5'-GMP (and 5'-IMP). Because the 3'-phosphate group cannot closely approach the metal inner coordination sphere, the greater stability for the 3'-GMP 1:2 adduct reflects the more favorable G N1H-phosphate interligand GMP-GMP interactions for 3'-GMP vs 5'-GMP (G=guanine base derivative). This type of interaction is known for platinum adducts. In 1:2 adducts the bound nucleotides are inequivalent, prompting us to perform mixed 5'-GMP/3'-GMP experiments, leading to the observation of major (M) and minor (m) mixed Re/5'-GMP/3'-GMP 1:1:1 adducts. The order of abundance at equilibrium in a typical experiment was M>bis 3'-GMP>m>or=bis 5'-GMP. This stability order was rationalized by invoking the phosphate interactions described above. When methionine and 5'-GMP were allowed to compete for fac-[Re(CO)3(H2O)3]+, the Re/5'-GMP 1:1 adduct was the kinetic product and the S-bound Re/methionine adduct was the thermodynamic product, a result opposite to that typically found for cisplatin.     

New monodentate amidine superbasic ligands with a single configuration in fac-[Re(CO)3(5,5'- or 6,6'-Me2bipyridine)(amidine)]BF4 complexes

Treatment of two precursors, fac-[Re(CO)(3)(L)(CH(3)CN)]BF(4) [L = 5,5'-dimethyl-2,2'-bipyridine (5,5'-Me(2)bipy) (1) and 6,6'-dimethyl-2,2'-bipyridine (6,6'-Me(2)bipy) (2)], with five C(2)-symmetrical saturated heterocyclic amines yielded 10 new amidine complexes, fac-[Re(CO)(3)(L)(HNC(CH(3))N(CH(2)CH(2))(2)Y)]BF(4) [Y = CH(2), (CH(2))(2), (CH(2))(3), NH, or O]. All 10 complexes possess the novel feature of having only one isomer (amidine E configuration), as established by crystallographic and (1)H NMR spectroscopic methods. We are confident that NMR signals of the other possible isomer (amidine Z configuration) would have been detected, if it were present. Isomers are readily detected in closely related amidine complexes because the double-bond character of the amidine C-N3 bond (N3 is bound to Re) leads to slow E to Z isomer interchange. The new fac-[Re(CO)(3)(L)(HNC(CH(3))N(CH(2)CH(2))(2)Y)]BF(4) complexes have C-N3 bonds with essentially identical double-bond character. However, the reason that the Z isomer is so unstable as to be undetectable in the new complexes is undoubtedly because of unfavorable clashes between the equatorial ligands and the bulky N(CH(2)CH(2))(2)Y ring moiety of the axial amidine ligand. The amidine formation reactions in acetonitrile (25 °C) proceeded more easily with 2 than with 1, indicating that the distortion in 6,6'-Me(2)bipy resulting from the proximity of the methyl substituents to the inner coordination sphere enhanced the reactivity of the coordinated CH(3)CN. Reaction times for 1 and 2 exhibited a similar dependence on the basicity and ring size of the heterocyclic amine reactants. Moreover, when the product of the reaction of 1 with piperidine, fac-[Re(CO)(3)(5,5'-Me(2)bipy)(HNC(CH(3))N(CH(2)CH(2))(2)CH(2))]BF(4), was challenged in acetonitrile-d(3) or CDCl(3) with a 5-fold excess of the strong 4-dimethylaminopyridine ligand, there was no evidence for replacement of the amidine ligand after two months, thus establishing that the piperidinylamidine ligand is a robust ligand. This chemistry offers promise as a suitable means for preparing isomerically pure conjugated fac-[(99m)Tc(CO)(3)L](n±) imaging agents, including conjugates with known bioactive heterocyclic amines.     

(S)-(2-(2'-Pyridyl)ethyl)cysteamine and (S)-(2-(2'-pyridyl)ethyl)-d,l-homocysteine as ligands for the "fac-[M(CO)(3)](+)" (M = Re, (99m)Tc) core

The reaction of fac-[NEt(4)](2)[Re(CO)(3)Br(3)] with (S)-(2-(2'-pyridyl)ethyl)cysteamine, L(1), in methanol leads to the formation of the cationic fac-[Re(CO)(3)(NSN)][Br] complex, 1, with coordination of the nitrogen of the pyridine, the sulfur of the thioether, and the nitrogen of the primary amine. When fac-[NEt(4)](2)[Re(CO)(3)Br(3)] reacts with the homocysteine derivative (S)-(2-(2'-pyridyl)ethyl)-d,l-homocysteine, L(2), the neutral fac-Re(CO)(3)(NSO) complex, 2, is produced with coordination of the nitrogen of the primary amine, the sulfur of the thioether, and the oxygen of the carboxylate group, while the pyridine ring remains uncoordinated. The analogous technetium-99m complexes, 1' and 2', were also prepared quantitatively by the reaction of L(1) and L(2) with the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor at 70 degrees C in water. Given that both (S)-(2-(2'-pyridyl)ethyl)cysteamine and homocysteine can be easily N- or S-derivatized by a bioactive molecule of interest, both the NSN or NSO ligand systems could be used to develop target-specific radiopharmaceuticals for diagnosis and therapy.     

Rhenium(I)-induced cyclization of thiosemicarbazones derived from beta-keto esters

The reactions of methylacetoacetate and ethyl 2-methylacetoacetate thiosemicarbazones (H(2)L(A) and H(2)L(B), respectively) with [ReX(CO)(5)] and [ReX(CO)(3)(CH(3)CN)(2)] (X = Cl, Br) were explored under various experimental conditions. Besides the adducts fac-[ReX(CO)(3)(H(2)L)], in which the rhenium is coordinated to three carbonyl groups, the X anion, and the N,S-bidentate thiosemicarbazone ligand, the following complexes were also isolated: fac-[ReBr(CO)(3)(Hpyz(B))], the tetrameric complexes fac-[Re(pyz(A))(CO)(3)](4) and fac-[Re(pyz(B))(CO)(3)](4), and fac-[Re(pyz(B))(CO)(3)(H(2)O)] (where Hpyz(A) and Hpyz(B) are pyrazolones derived by cyclization of H(2)L(A) and H(2)L(B), respectively). The cyclization reactions were monitored by (1)H NMR spectroscopy and the complexes isolated were identified by elemental analysis, mass spectrometry, IR and (1)H NMR spectroscopy, and in some cases by X-ray diffractometry. The isolation and the full structural identification of the rather unusual fac-[ReBr(CO)(3)(Hpyz(B))], which contains the enol form of the pyrazolone ligand, affords new insight into the cyclization of thiosemicarbazones derived from beta-keto esters.     

fac-[Re(CO)3(dmso-O)3](CF3SO3): a new versatile and efficient Re(I) precursor for the preparation of mono and polynuclear compounds containing fac-[Re(CO)3]+ fragments

We show here that the new complex fac-[Re(CO)3(dmso-O)3](CF3SO3) (1), efficiently prepared in one step from [ReBr(CO)5] and featuring a broad range of solubility, is, in general, a better precursor for the one-step synthesis of mono- and polynuclear inorganic compounds containing fac-[Re(CO)3]+ fragments compared to the commonly used (NEt4)2fac-[ReBr3(CO)3] and fac-[Re(CO)3(CH3CN)3](Y) (Y = PF6, BF4, ClO4) species. Compound 1 is the first example of a Re(I)-dmso complex structurally characterized and confirms the rule that dmso is always O-bonded when trans to CO. The reactivity of 1 was tested in the one-step preparation of several new and known complexes. The O-bonded sulfoxides of 1 are replaced under mild conditions by tri- (L3) and bidentate ligands (L2) to produce fac-[Re(CO)3(L3)]+ and fac-[Re(CO)3(L2)(dmso-O)]+ compounds, respectively. An excess of monodentate ligands (L) and more forcing conditions are needed to prepare fac-[Re(CO)3(L)3]+ compounds. The new compounds include fac-[Re(CO)3(bipy)(dmso-O)](CF3SO3) (4), that turned out to be an excellent precursor for binding the luminescent fac-[Re(CO)3(bipy)]+ fragment to polytopic ligands for the construction of more elaborate assemblies. One example reported here is the two-step preparation of fac-[{Re(CO)3(bipy)}(mu-4,4'-bipy){Ru(TPP)(CO)}](CF3SO3) (8) (TPP = tetraphenylporphyrin). The X-ray structures of the new compounds 1, 4, of the bis-porphyrin complex fac-[Re(CO)3Cl(4'MPyP)2] (13) (4'MPyP = 5-(4'pyridyl)-10,15,20-triphenylporphyrin), and of the rhenium-cyclophane [{(CO)3Re(mu-OH)2Re(CO)3}2(micro-4,4'-bipy)2] (15), among others, are described. Compound 1 might find useful applications in supramolecular chemistry (metal-mediated assembly of large architectures), in the in situ preparation of stable Re compounds to be used in nuclear medicine, and for the labeling of biomolecules.     

Rhenium-to-benzoylpyridine and rhenium-to-bipyridine MLCT excited states of fac-[Re(Cl)(4-benzoylpyridine)(2)(CO)(3)] and fac-[Re(4-benzoylpyridine)(CO)(3)(bpy)](+): a time-resolved spectroscopic and spectroelectrochemical study

The lowest allowed electronic transition of fac-[Re(Cl)(CO)(3)(bopy)(2)] (bopy = 4-benzoylpyridine) has a Re --> bopy MLCT character, as revealed by UV-vis and stationary resonance Raman spectroscopy. Accordingly, the lowest-lying, long-lived, excited state is Re --> bopy (3)MLCT. Electronic depopulation of the Re(CO)(3) unit and population of a bopy pi orbital upon excitation are evident by the upward shift of nu(CO) vibrations and a downward shift of the ketone nu(C=O) vibration, respectively, seen in picosecond time-resolved IR spectra. Moreover, reduction of a single bopy ligand in the (3)MLCT excited state is indicated by time-resolved visible and resonance Raman (TR(3)) spectra that show features typical of bopy(*)(-). In contrast, the lowest allowed electronic transition and lowest-lying excited state of a new complex fac-[Re(bopy)(CO)(3)(bpy)](+) (bpy = 2,2'-bipyridine) have been identified as Re --> bpy MLCT with no involvement of the bopy ligand, despite the fact that the first reduction of this complex is bopy-localized, as was proven spectroelectrochemically. This is a rare case in which the localizations of the lowest MLCT excitation and the first reduction are different. (3)MLCT excited states of both fac-[Re(Cl)(CO)(3)(bopy)(2)] and fac-[Re(bopy)(CO)(3)(bpy)](+) are initially formed vibrationally hot. Their relaxation is manifested by picosecond dynamic shifts of nu(C(triple bond)O) IR bands. The X-ray structure of fac-[Re(bopy)(CO)(3)(bpy)]PF(6).CH(3)CN has been determined.     

Investigation of mixed oxidation state cyanide-bridged Re(V)oxo (acac(2)en/pn) and Re(I)(bipy)(CO)3 complexes

A series of cyanide-bridged complexes that combine a low-valent photoacceptor rhenium(I) metal center with an electroactive midvalent rhenium(V) complex were prepared. The synthesis involved the preparation of novel asymmetric rhenium(V) oxo compounds, cis-Re(V)O(CN)(acac(2)en) (1) and cis-Re(V)O(CN)(acac(2)pn) (2), formed by reacting trans-[Re(V)O(OH(2))(acac(2)en)]Cl or trans-Re(V)O(acac(2)pn)Cl with [NBu(4)][CN]. The μ-bridged cyanide mixed-oxidation Re(V)-Re(I) complexes were prepared by incubating the asymmetric complexes, 1 or 2, with fac-[Re(I)(bipy)(CO)(3)][OTf] to yield cis-[Re(V)O(acac(2)en)(μ-CN-1κC:2κN)-fac-Re(I)(bipy)(CO)(3)][PF(6)] (3) and [cis-Re(V)O(acac(2)pn)(μ-CN-1κC:2κN)-fac-Re(I)(bipy)(CO)(3)][PF(6)] (4), respectively.     

Development of novel water-soluble, organometallic compounds for potential use in nuclear medicine: synthesis, characterization, and (1)H and (31)P NMR investigations of the complexes fac-[ReBr(CO)3L] (L=bis(bis(hydroxymethyl)phosphino)ethane, bis(bis(hydroxymethyl)phosphino)benzene)

The bidentate, water-soluble phosphine ligands, bis(bis(hydroxymethyl)phosphino)benzene (HMPB, 1) and bis(bis(hydroxymethyl)phosphino)ethane (HMPE, 2) were reacted with the organometallic precursor fac-[ReBr(3)(CO)(3)](2-), 3, to produce the complexes fac-[Re(OH(2))(CO)(3)L](+) and fac-[ReBr(CO)(3)L] (L = HMPE, HMPB), respectively, in good yields. The rhenium complexes fac-[ReBr(CO)(3)HMPB], 5, and fac-[ ReBr(CO)(3)HMPE], 8, were characterized using (1)H and (31)P NMR spectroscopy. The structure of fac-[ReBr(CO)(3)HMPB] was confirmed by single-crystal X-ray spectroscopy. The substitution reactions of HMPE/HMPB with the rhenium precursor 3 in aqueous solution were monitored using time-dependent (31)P NMR techniques. A significant discrepancy in the reaction kinetics and the substitution mechanism between the two bidentate ligands could be observed presumably due to the different chemical backbones.     

Thiol- and thioether-based bifunctional chelates for the {M(CO)3}+ core (M = Tc, Re)

By analogy to the recently described single amino acid chelate (SAAC) technology for complexation of the {M(CO)3}+ core (M = Tc, Re), a series of tridentate ligands containing thiolate and thioether groups, as well as amino and pyridyl nitrogen donors, have been prepared: (NC5H4CH2)2NCH2CH2SEt (L1); (NC5H4CH2)2NCH2CH2SH (L2); NC5H4CH2N(CH2CH2SH)2 (L3); (NC5H4CH2)N(CH2CH2SH)(CH2CO2R) [R = H (L4); R = -C2H5 (L5). The {Re(CO)3}+ core complexes of L1-L5 were prepared by the reaction of [Re(CO)3(H2O)3]Br or [NEt4]2[Re(CO)3Br3] with the appropriate ligand in methanol and characterized by infrared spectroscopy, 1H and 13C NMR spectroscopy, mass spectrometry, and in the case of [Re(CO)3(L2)] (Re-2) and [Re(CO)3(L1)Re(CO)3Br2] (Re-1a) by X-ray crystallography. The structure of Re-2 consists of discrete neutral monomers with a fac-Re(CO)3 coordination unit and the remaining coordination sites occupied by the amine, pyridyl, and thiolate donors of L2, leaving a pendant pyridyl arm. In contrast, the structure of Re-1a consists of discrete binuclear units, constructed from a {Re(CO)3(L1)}+ subunit linked to a {Re(CO)3Br2}- group through the sulfur donor of the pendant thioether arm. The series of complexes establishes that thiolate donors are effective ligands for the {M(CO)3}+ core and that a qualitative ordering of the coordination preferences of the core may be proposed: pyridyl nitrogen approximately thiolate > carboxylate > thioether sulfur > thiophene sulfur. The ligands L1 and L2 react cleanly with [99mTc(CO)3(H2O)3]+ in H2O/DMSO to give [99mTc(CO)3(L1)]+ (99m)Tc-1) and [99mTc(CO)3(L2)] (99mTc-2), respectively, in ca. 90% yield after HPLC purification. The Tc analogues 99mTc-1 and 99mTc-2 were subjected to ligand challenges by incubating each in the presence of 1000-fold excesses of both cysteine and histidine. The radiochromatograms showed greater than 95% recovery of the complexes.     

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

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.     

Re(CO)(3) complexes synthesized via an improved preparation of aqueous fac-[Re(CO)(3)(H(2)O)(3)](+) as an aid in assessing (99m)Tc imaging agents. Structural characterization and solution behavior of complexes with thioether-bearing amino acids as tridentate ligands

Parallel studies of the preparation of Re and (99m)Tc agents aid in interpreting the nature of tracer (99m)Tc radiopharmaceuticals. Aqueous solutions of the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) cation are gaining wide use and are readily prepared, but such solutions of the fac-[Re(CO)(3)(H(2)O)(3)](+) cation (1) are not so easily accessible. Herein we describe a new, reliable, and straightforward preparation of aqueous solutions of 1, characterized by HPLC and ESI-MS. Treatment of solutions of 1 with thioether-bearing amino acids, AAH = S-methyl-l-cysteine (MECYSH), S-propyl-l-cysteine (PRCYSH), and methionine (METH), gave high yields of fac-Re(CO)(3)AA complexes. X-ray crystallographic and NMR analyses indicated that MECYS(-), PRCYS(-), and MET(-) were bound in fac-Re(CO)(3)AA complexes as tridentate monoanionic ligands through amino, thioether, and alpha-carboxyl groups. In CD(3)OD, (1)H NMR spectra have broad signals but have two sets of signals at -10 degrees C, consistent with two isomers with different configurations at the pyramidal sulfur; these interconvert slowly on the NMR time scale at low temperatures. Indeed, the crystal structure of the fac-Re(CO)(3)(PRCYS) reveals a mixture of the two possible diastereoisomers. S-(Carboxymethyl)-l-cysteine (CCMH(2)) and 1 gave two products, 5A (kinetically favored) and 5B (thermodynamically favored). X-ray crystallographic analyses of a crystal of 5B and of a 1:1 cocrystal of 5A and 5B showed that 5A and 5B are diastereoisomers with the CCMH(-) alpha-carboxyl group dangling. In addition to the amino and thioether groups, the S-(carboxymethyl) carboxyl group is coordinated, a feature that slows interconversion of diastereoisomers relative to the other fac-Re(CO)(3)AA complexes because interconversion can now occur only after the rupture of Re-ligand bonds. These N, O, and S tridentate adducts are quite stable, and the grouping has promise in (99m)Tc(CO)(3) tracer development.     

Relevance of the ligand exchange rate and mechanism of fac-[(CO)3M(H2O)3]+ (M = Mn, Tc, Re) complexes for new radiopharmaceuticals

The water exchange process on fac-[(CO)3Mn(H2O)3]+ and fac-[(CO)3Tc(H2O)3]+ was kinetically investigated by 17O NMR as a function of the acidity, temperature, and pressure. Up to pH 6.3 and 4.4, respectively, the exchange rate is not affected by the acidity, thus demonstrating that the contribution of the monohydroxo species fac-[(CO)3M(OH)(H2O)2] is not significant, which correlates well with a higher pKa for these complexes compared to the homologue fac-[(CO)3Re(H2O)3]+ complex. The water exchange rate K298ex/s(-1) (DeltaHex double dagger/kJ mol(-1); DeltaSex double dagger/J mol(-1) K(-1); DeltaV double dagger/cm3 mol-1) decreases down group 7 from Mn to Tc and Re: 23 (72.5; +24.4; +7.1) > 0.49 (78.3; +11.7; +3.8) > 5.4 x 10(-3) (90.3; +14.5; -). For the Mn complex only, an O exchange on the carbonyl ligand could be measured (K338co = 4.3 x 10(-6) s(-1)), which is several orders of magnitude slower than the water exchange. In the case of the Tc complex, the coupling between 17O (I = 5/2) and 99Tc (I = 9/2) nuclear spins has been observed (1J99Tc,17O = 80 +/- 5 Hz). The substitution of water in fac-[(CO)3M(H2O)3]+ by dimethyl sulfide (DMS) is slightly faster than that by CH3CN: 3 times faster for Mn, 1.5 times faster for Tc, and 1.2 times faster for Re. The pressure dependence behavior is different for Mn and Re. For Mn, the change in volume to reach the transition state is always clearly positive (water exchange, CH3CN, DMS), indicating an Id mechanism. In the case of Re, an Id/Ia changeover is assigned on the basis of reaction profiles with a strong volume maximum for pyrazine and a minimum for DMS as the entering ligand.     

Reactions of M(CO)5X (M = Mn, Re; X = Cl, Br) with (Ph2PCH2)3CCH3 (P3) and (Ph2P(CH2)2)3P (P3P'): synthetic, spectroscopic, electrochemical, and electrospray mass spectrometric studies

The reactions of M(CO)5X (M = Mn, Re; X = Cl, Br) with (Ph2PCH2)3CCH3 (P3) and (Ph2P(CH2)2)3P (P3P') are investigated, and the products are characterized by IR, NMR (31P and 13C), and electrospray mass spectrometric (ESMS) techniques. With P3, the major products are fac-M(CO)3(eta 2-P3)X (syn and anti isomers) and cis,fac-M(CO)2(eta 3-P3)X, and with P3P', the major product for each metal is cis,mer-M(CO)2(eta 3-P3P')X, but cis-[M(CO)2(eta 4-P3P')]X and fac-[Re(CO)3(eta 3-P3P')]X are also characterized. Addition of MeI to those complexes containing pendant phosphine groups produces the corresponding phosphonium cations without affecting the remainder of the molecule. On the voltammetric time scale, electrochemical oxidation of cis,fac-Mn(CO)2(eta 3-P3)X yields the corresponding 17e cation cis,fac-[Mn(CO)2(eta 3-P3)X]+, but on the longer time scale of exhaustive electrolysis or chemical oxidation, the product is fac-[Mn(CO)3(eta 3-P3)]+. In contrast, the rhenium cation cis,fac-[Re(CO)2(eta 3-P3)X]+ is stable on the synthetic time scale, but upon oxidation of cis,fac-Re(CO)2(eta 3-P3)X with NOBF4, the final product is the 18e [Re(CO)(NO)(eta 3-P3)X]+. cis,mer-Mn(CO)2(eta 3-P3P')X is reversibly oxidized to cis,mer-[Mn(CO)2(eta 3-P3P')X]+ on the voltammetric time scale, but on the longer synthetic time scale, the product isomerizes to trans-[Mn(CO)2(eta 3-P3P')X]+, which can be reduced to trans-Mn(CO)2(eta 3-P3P')X. Upon voltammetric oxidation, the corresponding rhenium complexes show an initial irreversible response associated with the pendant phosphine group prior to the reversible oxidation of the metal on the synthetic time scale; spectroscopic data indicate formation of cis,mer-Re(CO)2(eta 3-P3P'O)X. The complex cis,mer-[Re(CO)2(eta 3-P3P'Me)X]+ shows only the reversible metal oxidation response. ESMS data are obtained directly for the methylated cationic complexes, and neutral complexes are either oxidized or adducted with sodium ions to produce cationic species.     

Involvement of a binuclear species with the Re-C(O)O-Re moiety in CO2 reduction catalyzed by tricarbonyl rhenium(I) complexes with diimine ligands: strikingly slow formation of the Re-Re and Re-C(O)O-Re species from Re(dmb)(CO)3S (dmb = 4,4'-dimethyl-2,2'-bipyridine, S = solvent)

Excited-state properties of fac-[Re(dmb)(CO)(3)(CH(3)CN)]PF(6), [Re(dmb)(CO)(3)](2) (where dmb = 4,4'-dimethyl-2,2'-bipyridine), and other tricarbonyl rhenium(I) complexes were investigated by transient FTIR and UV-vis spectroscopy in CH(3)CN or THF. The one-electron reduced monomer, Re(dmb)(CO)(3)S (S = CH(3)CN or THF), can be prepared either by reductive quenching of the excited states of fac-[Re(dmb)(CO)(3)(CH(3)CN)]PF(6) or by homolysis of [Re(dmb)(CO)(3)](2). In the reduced monomer's ground state, the odd electron resides on the dmb ligand rather than on the metal center. Re(dmb)(CO)(3)S dimerizes slowly in THF, k(d) = 40 +/- 5 M(-1) s(-1). This rate constant is much smaller than those of other organometallic radicals which are typically 10(9) M(-1) s(-1). The slower rate suggests that the equilibrium between the ligand-centered and metal-centered radicals is very unfavorable (K approximately 10(-4)). The reaction of Re(dmb)(CO)(3)S with CO(2) is slow and competes with the dimerization. Photolysis of [Re(dmb)(CO)(3)](2) in the presence of CO(2) produces CO with a 25-50% yield based on [Re]. A CO(2) bridged dimer, (CO)(3)(dmb)Re-CO(O)-Re(dmb)(CO)(3) is identified as an intermediate. Both [Re(dmb)(CO)(3)](2)(OCO(2)) and Re(dmb)(CO)(3)(OC(O)OH) are detected as oxidation products; however, the previously reported formato-rhenium species is not detected.     

Structure, reactivity and solution behaviour of [Re(ser)(7-MeG)(CO)(3)] and [Re(ser)(3-pic)(CO)(3)]: "nucleoside-mimicking" complexes based on the fac-[Re(CO)(3)](+) moiety

The fac-[Re(CO)(3)](+) moiety was reacted with the amino acid serine (D- and L-ser) and with 7-methylguanine (7-MeG), 3-methylpyridine (3-pic) or adenine (ade) to yield novel complexes intended as nucleoside-mimicking compounds. Reaction of [Re(H(2)O)(3)(CO)(3)](+)(1) with L-ser yields the complex [Re(L-ser)(2)(CO)(3)](L-2). X-Ray structure analysis of L-2 reveals that one of the two amino acids is bound to the metal centre in a bidentate fashion while the other amino acid is bound as a zwitterion via the carboxylate oxygen only. Reaction of L-2 and of [Re(D-ser)(2)(CO)(3)](D-2) with 7-MeG yields complexes [Re(L-ser)(7-MeG)(CO)(3)](L-3) and [Re(D-ser)(7-MeG)(CO)(3)](D-3) respectively. Complexes L-3 and D-3 are received as a mixture of diastereomers. If 3-pic is used instead of 7-MeG complex [Re(L-ser)(3-pic)(CO)(3)](L-4) is obtained in good yield, while interaction of L-2 with ade gives a mixture of five distinct species. Crystallization gave one single diastereomer for L-3 and D-3 and the two forms for 4 respectively. X-Ray structure analyses reveal that in all cases the amino acid is bound in a chelate fashion with the base occupying the sixth co-ordination site. When crystals of either 2 or 3 are dissolved in a CD(3)OD/D(2)O mixture (1:1, 293 K) rapid transformation to the diastereomeric mixture is observed. While for L-2 this reorganisation is fast on the NMR time scale even at 193 K, the rate constant for the rearrangement of L-3 and D-3 is 1.36 +/- 0.24 x 10(-2) s(-1) at 293 K.     

Luminescent rhenium(I)-dipyrrinato complexes

The first Re(I)-dipyrrinato complexes are reported. Complexes with the general formulas fac-[ReL(CO)(3)Cl](-), fac-[ReL(CO)(3)PR(3)], and [ReL(CO)(2)(PR(3))(PR'(3))] have been prepared, where L is one of a series of meso-aryl dipyrrinato ligands. Access to these complexes proceeds via the reaction of [Re(CO)(5)Cl] with the dipyrrin (LH) to produce fac-[ReL(CO)(3)Cl](-). A subsequent reaction with PR(3) (R = phenyl, butyl) leads to displacement of the chloride ligand to generate fac-[ReL(CO)(3)PR(3)], and further reaction with PR'(3) leads to the displacement of the CO ligand trans to the first PR(3) ligand to give trans(P), cis(C)-[ReL(CO)(2)(PR(3))(PR'(3))]. The structures of the complexes were determined in the solid state by X-ray crystallography and in solution by (1)H NMR spectroscopy. Electronic absorption spectroscopy reveals a prominent band in the visible region at relatively low energy (472-491 nm) for all complexes, which is assigned as a π-π* transition of the dipyrrin chromophore. Weak emission (λ(ex) = 485 nm, quantum yields <0.01) was observed for [ReL(CO)(3)Cl](-) and [ReL(CO)(3)PR(3)] complexes, but no emission was generally evident from the [ReL(CO)(2)(PR(3))(PR'(3))] complexes. On the basis of the large Stokes shift (~6000 cm(-1)), the emission is ascribed to phosphorescence from a triplet excited state. The emission intensity is sensitive to dissolved oxygen and methyl viologen; a Stern-Volmer plot in the latter case gave a straight line. Photochemical ligand substitution reactions of [ReL(CO)(3)PR(3)] were induced by excitation with a 355 nm laser in acetonitrile. [ReL(CO)(2)(PR(3))(CH(3)CN)] is formed as a putative intermediate, which reacts thermally with added PR'(3) to produce [ReL(CO)(2)(PR(3))(PR'(3))] complexes.