Iron oxide-filled micelles as ligands for fac-[M(CO)3]+ (M = (99m)Tc, Re)

Magnetite-filled micelles capture fac-[M(OH(2))(3)(CO)(3)](+) complexes (M = (99m)Tc, Re), creating versatile self-assembled constructs for multimodal SPECT/MR/optical imaging and radiopharmaceutical guided delivery.     

Pyridine-tert-nitrogen-phenol ligands: N,N,O-Type tripodal chelates for the [M(CO)3]+ core (M = Re, Tc)

The design rationale, synthesis, and preliminary radiolabeling evaluation of new N,N,O-type pyridyl- tert-nitrogen-phenol ligands for the [M(CO) 3] (+) core, where M = (99m)Tc or Re, are described. The capability of the ligands to bind this technetium core is initially demonstrated by using the cold surrogate [Re(CO) 3] (+). NMR studies of the relevant rhenium tricarbonyl complexes indicate the formation of either a monomeric or a possible dimeric complex with each phenolic O atom bridging between two metal centers. Labeling with [ (99m)Tc(CO) 3] (+) provided further insight into the differences in complex formation on the dilute, no carrier added, level compared to the macroscopic scale at which the Re (I) counterparts were made. These new tridentate, monoanionic ligands are competent chelates in binding the [ (99m)Tc(CO) 3] (+) core because radiolabeling yields ranged from 85 to 99% and the resulting complexes were stable to cysteine and histidine challenges for as long as 24 h.     

N-(2-Mercaptoethyl)picolylamine as a diaminomonothiolate ligand for the "fac-[Re(CO)3]+" core

N-(2-Mercaptoethyl)picolylamine (MEPAH) was studied as a potentially biologically relevant ligand for the "fac-[M(CO)(3)](+)" core (M = Re, (99)Tc, (99m)Tc). To this end, the complex Re(CO)(3)(MEPA) was synthesized. The reaction of MEPAH with fac-[Re(CO)(3)(MeCN)(3)](+) took place over the course of seconds, showing the high affinity possessed by this ligand for the "fac-[Re(CO)(3)](+)" core. A single-crystal X-ray diffraction study was performed confirming the nature of Re(CO)(3)(MEPA), a rare mononuclear rhenium(I) thiolate complex. Additional exploration into derivatization of the ligand backbone has afforded the analogous N-ethyl complex, Re(CO)(3)(MEPA-NEt). The high affinity of the ligand for the metal coupled with the ease of its derivatization implies that utilization of this ligand system for the purposes of (99m)Tc-radiopharmaceutical development is promising.     

The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, (99m)Tc) radiopharmaceuticals

Facile reactivity of hydrazides and aldehydes was explored as potential coupling partners for incorporation into M(CO)(3) (M = Re, (99m)Tc) based radiopharmaceuticals. Both 'click, then chelate' and 'prelabel, then click' synthetic routes produced identical products in high yields and lacked metal-hydrazide/-hydrazone interactions, highlighting the potential of this click strategy.     

Carboranes as ligands for the preparation of organometallic Tc and Re Radiopharmaceuticals. Synthesis of [M(CO)(3)(eta-2,3-C(2)B(9)H(11))](-) and rac-[M(CO)(3)(eta-2-R-2,3-C(2)B(9)H(10))](-) (M = Re, (99)Tc; R = CH(2)CH(2)CO(2)H) from [M(CO)(3)Br(3)](2-)

A new and high yielding method for the synthesis of [M(CO)(3)(eta(5)-2,3-C(2)B(9)H(11))](-) and the bifunctional metal complexes, rac-[M(CO)(3)(eta(5)-2-R-2,3-C(2)B(9)H(10))](-) (R = CH(2)CH(2)CO(2)H), from [M(CO)(3)Br(3)](2)(-) (M = Re, (99)Tc) was developed. The general approach entailed the addition of nido-[(C(2)B(9)H(12))(-)], or the acid substituted analogue, to [M(CO)(3)Br(3)](2)(-) (M = Re, (99)Tc) in the presence of TlOEt in THF. It was also possible to prepare the reported products in water using sodium carbonate in place of TlOEt. The reported approach led to the preparation, and X-ray crystallographic structure determination, of the first Tc-carborane complex reported to date (a = 13.606(17) A, b = 10.685(13) A, c = 15.534(16) A, alpha = gamma = 90 degrees, beta = 111.84(2) degrees). Because of the stabilities of the metal complexes, and the fact that the compounds can be prepared in water, the bifunctional derivatives can be considered as novel synthons for the preparation of organometallic (99m)Tc and (186/188)Re radiopharmaceuticals.     

Cell-specific and nuclear targeting with [M(CO)(3)](+) (M=(99m)Tc, Re)-based complexes conjugated to acridine orange and bombesin

Receptor-specific nuclear targeting requires trifunctional metal complexes. We have synthesized [M(L(2)-pept)(L(1)-acr)(CO)(3)] (pept=peptide; acr=acridine-based agent) in which the fac-[M(CO)(3)](+) moiety (1st function, M=(99m)Tc, Re) couples an acridine-based nuclear-targeting agent (2nd function, L(1)-acr) and the specific cell-receptor-binding peptide bombesin (3rd function, L(2)-pept). The metal-mediated coupling is based on the mixed ligand [2+1] principle. The nuclear targeting agents have been derivatised with an isocyanide group for monodentate (L(1)) and bombesin (BBN) with a bidentate ligand (L(2)) for complexation to fac-[M(CO)(3)](+). For nuclear uptake studies, the model complexes [Re(L(2))(L(1)-acr)(CO)(3)] (L(2)=pyridine-2-carboxylic acid and pyridine-2,4-dicarboxylic acid) were synthesized and structurally characterized. We selected acridine derivatives as nuclear-targeting agents, because they are very good nucleus-staining agents and exhibit strong fluorescence. Despite the bulky metal complexes attached to acridine, all [Re(L(2))(L(1)-acr)(CO)(3)] showed high accumulation in the nuclei of PC3 and B16F1 cells, as evidenced by fluorescence microscopy. For radiopharmaceutical purposes, the (99m)Tc analogues have been prepared and radioactivity distribution confirmed the fluorescence results. Coupling of BBN to L(2) gave the receptor-selective complexes [M(L(2)-BBN)(L(1)-acr)(CO)(3)]. Whereas no internalization was found with B16F1 cells, fluorescence microscopy on PC3 cells bearing the BBN receptor showed high and rapid uptake by receptor-mediated endocytosis into the cytoplasm, but not into the nucleus.     

Site directed maleimide bifunctional chelators for the M(CO)3+ core (M =(99m)Tc, Re)

A series of bifunctional chelates containing a tridentate donor set for complexation of the M(CO)3+ core and a maleimide group for site-specific coupling to peptides and proteins containing free thiol groups has been prepared and their Re(CO)3+ complexes and glutathione conjugates structurally characterized. The flexibility of design allows preparation of ligands suitable for both fluorescence imaging, radioimaging and radiotherapeutic studies of proteins and peptides as well as other biopolymers using site specific conjugation.     

Design and synthesis of a bombesin peptide-conjugated tripodal phosphino dithioether ligand topology for the stabilization of the fac-[M(CO)3]+ core (M=(99 m)Tc or Re)

A new tumor-seeking tridentate topology consisting of a phosphino dithioether ((HOCH(2))(2)PCH(2)CH(2)S(CH(2))(n)CH(2)SR; PS(2)) ligand framework for the production of kinetically inert and in vivo stable facial [(99m)Tc(CO)(3)(PS(2))](+) or [Re(CO)(3)(PS(2))](+) is described. The X-ray crystal structure of fac-Re(CO)(3)(PS(2))PF(6) is reported. The bioconjugation strategies for incorporating bombesin (BBN) peptides on to the PS(2) tripodal framework and, thereby, de novo designing of GRP receptor-seeking Tc(PS(2)-BBN)(CO)(3) are developed.     

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.     

Characterization and application of the fac-[188Re(CO)3(H2O)3]+ core

Summary Fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ was synthesized with an overall radiochemical yield of 80±5%, and more than 95% radiochemical purity after a QMA Sep-Pak column separation. Fac-[Re(CO)₃(H₂O)₃]⁺ was also synthesized as a reference sample. The structure of the precursor, fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺, was confirmed by high performance of liquid chromatography (HPLC). MN-His (magnetic nanoparticles coated with silica and modified with an amino silane coupling agent, N-[3-(trimethyoxysilyl)propyl]-ethylenediamine (SG-Si900) and immobilized with histidine) was labeled with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ and an initial animal test of MN-His was conducted for a magnetic targeting study.     

Excited-state dynamics in fac-[Re(CO)3(Me4phen)(L)]+

Excited-state dynamics in fac-[Re(CO)(3)(Me(4)phen)(cis-L)](+) (Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline, L = 4-styrylpyridine (stpy) or 1,2-bis(4-pyridyl)ethylene (bpe)) were investigated by steady-state and time-resolved techniques. A complex equilibrium among three closely lying excited states, (3)IL(cis-L), (3)MLCT(Re→Me(4)phen), and (3)IL(Me(4)phen), has been established. Under UV irradiation, cis-to-trans isomerization of coordinated cis-L is observed with a quantum yield of 0.15 in acetonitrile solutions. This photoreaction competes with radiative decay from (3)MLCT(Re→Me(4)phen) and (3)IL(Me(4)phen) excited states, leading to a decrease in the emission quantum yield relative to the nonisomerizable complex fac-[Re(CO)(3)(Me(4)phen)(bpa)](+) (bpa = 1,2-bis(4-pyridyl)ethane). From temperature-dependent time-resolved emission measurements in solution and in poly(methyl methacrylate) (PMMA) films, energy barriers (ΔE(a)) for interconversion between (3)MLCT(Re→Me(4)phen) and (3)IL(Me(4)phen) emitting states were determined. For L = cis-stpy, ΔE(a) = 11 (920 cm(-1)) and 15 kJ mol(-1) (1254 cm(-1)) in 5:4 propionitrile/butyronitrile and PMMA, respectively. For L = cis-bpe, ΔE(a) = 13 kJ mol(-1) (1087 cm(-1)) in 5:4 propionitrile/butyronitrile. These energy barriers are sufficient to decrease the rate constant for internal conversion from higher-lying (3)IL(Me(4)phen) state to (3)MLCT(Re→Me(4)phen), k(i) ? 10(6) s(-1). The decrease in rate allows for the observation of intraligand phosphorescence, even in fluid medium at room temperature. Our results provide additional insight into the role of energy gap and excited-state dynamics on the photochemical and photophysical properties of Re(I) polypyridyl complexes.     

(Cp-R)M(CO)(3) ] (M=Re or (99m) Tc) Arylsulfonamide, Arylsulfamide, and Arylsulfamate Conjugates for Selective Targeting of Human Carbonic Anhydrase IX

Enhanced receptor selectivity: Carbonic anhydrase inhibitors are relevant for both cancer diagnosis and therapy. Combining non-radioactive Re compounds with their radioactive (99m) Tc homologs enables the use of identical molecules for therapy and imaging (theragnostic). The syntheses and in?vitro evaluation of [(Cp-R)M(CO)(3) ] (Cp=cyclopentadienyl, M=Re, (99m) Tc) with R being a highly potent carbonic-anhydrase-targeting vector is reported.     

Curcumin as the OO bidentate ligand in "2 + 1" complexes with the [M(CO)3]+ (M = Re, 99mTc) tricarbonyl core for radiodiagnostic applications

The synthesis and characterization of "2 + 1" complexes of the [M(CO)(3)](+) (M = Re, (99m)Tc) core with the β-diketones acetylacetone (complexes 2, 8) and curcumin (complexes 5, 10 and 6, 11) as bidentate OO ligands, and imidazole or isocyanocyclohexane as monodentate ligands is reported. The complexes were synthesized by reacting the [NEt(4)](2)[Re(CO)(3)Br(3)] precursor with the β-diketone to generate the intermediate aqua complex fac-Re(CO)(3)(OO)(H(2)O) that was isolated and characterized, followed by replacement of the labile water by the monodentate ligand. All complexes were characterized by mass spectrometry, NMR and IR spectroscopies, and elemental analysis. In the case of complex 2, bearing imidazole as the monodentate ligand, X-ray analysis was possible. The chemistry was successfully transferred at (99m)Tc tracer level. The curcumin complexes 5 and 6, as well as their intermediate aqua complex 4, that bear potential for radiopharmaceutical applications due to the wide spectrum of pharmacological activity of curcumin, were successfully tested for selective staining of β-amyloid plaques of Alzheimer's disease. The fact that the complexes maintain the affinity of the mother compound curcumin for β-amyloid plaques prompts for further exploration of their chemistry and biological properties as radioimaging probes.     

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.     

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.     

Toward novel DNA binding metal complexes: structure and basic kinetic data of [M(9MeG)2(CH3OH)(CO)3]+(M = 99Tc,Re)

To study the interaction of the fac-[M(CO)(3)](+) moiety (M = (99m)Tc, (188)Re) with DNA bases, we reacted [M(OH(2))(3)(CO)(3)](+) with 9-methylguanine (9-MeG), guanosine (G), and 2-deoxyguanosine (2dG). Two bases bind to the metal center via the N7 atoms. X-ray structure analysis of [(99)Tc(CH(3)OH)(9-MeG)(2)(CO)(3)](+) (4) (monoclinic, I2/a, a = 28.7533(14) A, b = 8.0631(4) A, c = 32.3600(15) A, beta = 91.543(6) degrees, V = 7499.6(6) A(3), Z = 8) and [Re(OH(2))(9-MeG)(2)(CO)(3)](+) (7) (monoclinic, P2(1)/n, a = 12.2873(11) A, b = 16.0707(13) A, c = 14.1809(16) A, beta = 103.361(12) degrees, V = 2724.4(5) A(3), Z = 4) reveals that the two bases are in a head-to-tail (HT) orientation. Kinetic studies show that the rates of substitution of the purine bases are comparable to that of one of the active forms of cisplatin. The bis-substituted complexes are generally less stable than the platinum adducts, and metalation of the bases is reversible.     

Synthesis, Structure, and Reactivities of [eta(2)-P(7)M(CO)(4)](3)(-), [eta(2)-HP(7)M(CO)(4)](2)(-), and [eta(2)-RP(7)M(CO)(4)](2)(-) Zintl Ion Complexes Where M = Mo, W

Ethylenediamine (en) solutions of [eta(4)-P(7)M(CO)(3)](3)(-) ions [M = W (1a), Mo (1b)] react under one atmosphere of CO to form microcrystalline yellow powders of [eta(2)-P(7)M(CO)(4)](3)(-) complexes [M = W (4a), Mo (4b)]. Compounds 4 are unstable, losing CO to re-form 1, but are highly nucleophilic and basic. They are protonated with methanol in en solvent giving [eta(2)-HP(7)M(CO)(4)](2)(-) ions (5) and are alkylated with R(4)N(+) salts in en solutions to give [eta(2)-RP(7)M(CO)(4)](2)(-) complexes (6) in good yields (R = alkyl). Compounds 5 and 6 can also be prepared by carbonylations of the [eta(4)-HP(7)M(CO)(3)](2)(-) (3) and [eta(4)-RP(7)M(CO)(3)](2)(-) (2) precursors, respectively. The carbonylations of 1-3 to form 4-6 require a change from eta(4)- to eta(2)-coordination of the P(7) cages in order to maintain 18-electron configurations at the metal centers. Comparative protonation/deprotonation studies show 4 to be more basic than 1. The compounds were characterized by IR and (1)H, (13)C, and (31)P NMR spectroscopic studies and microanalysis where appropriate. The [K(2,2,2-crypt)](+) salts of 5 were characterized by single crystal X-ray diffraction. For 5, the M-P bonds are very long (2.71(1) ?, average). The P(7)(3)(-) cages of 5 are not displaced by dppe. The P(7) cages in 4-6 have nortricyclane-like structures in contrast to the norbornadiene-type geometries observed for 1-3. (31)P NMR spectroscopic studies for 5-6 show C(1) symmetry in solution (seven inequivalent phosphorus nuclei), consistent with the structural studies for 5, and C(s)() symmetry for 4 (five phosphorus nuclei in a 2:2:1:1:1 ratio). Crystallographic data for [K(2,2,2-crypt)](2)[eta(2)-HP(7)W(CO)(4)].en: monoclinic, space group C2/c, a = 23.067(20) ?, b = 12.6931(13) ?, c = 21.433(2) ?, beta = 90.758(7) degrees, V = 6274.9(10) ?(3), Z = 4, R(F) = 0.0573, R(w)(F(2)) = 0.1409. For [K(2,2,2-crypt)](2)[eta(2)-HP(7)Mo(CO)(4)].en: monoclinic, space group C2/c, a = 22.848(2) ?, b = 12.528(2) ?, c = 21.460(2) ?, beta = 91.412(12) degrees, V = 6140.9(12) ?(3), Z = 4, R(F) = 0.0681, R(w)(F(2)) = 0.1399.     

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.     

Ultrafast excited-state dynamics preceding a ligand trans-cis isomerization of fac-[Re(Cl)(CO)3(t-4-styrylpyridine)2] and fac-[Re(t-4-styrylpyridine)(CO)3(2,2'-bipyridine)]+

UV-vis absorption and resonance Raman spectra of the complexes fac-[Re(Cl)(CO)3(stpy)2] and fac-[Re(stpy)(CO)3(bpy)]+ (stpy = t-4-styrylpyridine, bpy = 2,2'-bipyridine) show that their lowest absorption bands are dominated by stpy-localized intraligand (IL) pi pi* transitions. For the latter complex a Re --> bpy transition contributes to the low-energy part of the absorption band. Optical population of the 1IL excited state of fac-[Re(Cl)(CO)3(stpy)2] is followed by an intersystem crossing (< or =0.9 ps) to an 3IL state with the original planar trans geometry of the stpy ligand. This state undergoes a approximately 90 degrees rotation around the stpy C=C bond with a 11 ps time constant. An electronically excited species with an approximately perpendicular orientation of the phenyl and pyridine rings of the stpy ligand is formed. Conversion to the ground state and isomerization occurs in the nanosecond range. Intraligand excited states of fac-[Re(stpy)(CO)3(bpy)]+ show the same behavior. Moreover, it was found that the planar reactive 3IL excited state is rapidly and efficiently populated after optical excitation into the Re --> bpy 1MLCT excited state. A 1MLCT --> 3MLCT intersystem crossing takes place first with a time constant of 0.23 ps followed by an intramolecular energy transfer from the ReI(CO)3(bpy) chromophore to a stpy-localized 3IL state with a 3.5 ps time constant. The fast rate ensures complete conversion. Coordination of the stpy ligand to the ReI center thus switches the ligand trans-cis isomerization mechanism from singlet to triplet (intramolecular sensitization) and, in the case of fac-[Re(stpy)(CO)3(bpy)]+, opens an indirect pathway for population of the reactive 3IL excited state via MLCT states.     

Post-protein-binding reactivity and modifications of the fac-[Re(CO)3]+ core

The reactivity of the [Re(CO)(3)(H(2)O)(2)](+) complex coordinated to the His15 residue of HEW lysozyme is described. In the fully metalated protein (Lys-1), the Re ion retains its reactivity only toward selected ligands, while others induce a ligand-mediated demetalation of the enzyme. It is further shown that some of the complexes that may be "engineered" on the lysozyme do not react with the free protein even if present in solution in excess. The formation of stable metal adducts starting from Lys-1 was confirmed by X-ray crystallography.