The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine

The β emitting isotopes ¹⁸⁶Re and ¹⁸⁸Re are logical choices on which to base therapeutic radiopharmaceuticals that might be expected to be analogous to diagnostic radiopharmaceuticals based on ^99mTc. However, the chemistry of rhenium is sufficiently different from that of technetium so that the development of Re radiopharmaceuticals often cannot be predicated on the known chemistry and biological behavior of ^99mTc radiopharmaceuticals. The relevant chemical differences involve the greater stability of the higher oxidation states of Re (and thus the greater tendency of reduced Re radiopharmaceuticals to undergo re-oxidation to perrhenate), and the greater substitution inertness of reduced Re complexes. These differences are illustrated (1) in the preparation and use of ¹⁸⁶Re (Sn)-HEDP and ^99mTc(Sn)-HEDP diphosphonate radiopharmaceuticals designed, respectively, for palliative therapy and diagnosis of metastatic cancer to bone, and (2) in the preparation and biodistribution of tr-[¹⁸⁶Re(DMPE)₂Cl₂]⁺ and [¹⁸⁶Re(DMPE)₃]⁺, analogs to the potential myocardial perfusion imaging agents tr-[^99mTc(DMPE)₂Cl₂]⁺ and [^99mTc(DMPE)₃]⁺. [HEDP = (1-hydroxyethylidene)diphosphonate; DMPE = 1,2-bis(dimethylphosphino)ethane].     

Ethylenediamine- and propylenediaminediacetic acid derivatives as ligands for the “fac-[M(CO)3]” core (M = Re, Tc)

The reaction of Re(CO)₅Cl with o- or p-N-(nitrophenyl)ethylenediaminediacetic acid (H₂L¹, H₂L²) and o- or p-N-(nitrophenyl)propylenediaminediacetic acid (H₂L³, H₂L⁴) in methanol leads to the formation of stable anionic [Et₃NH][Re(CO)₃(L)] · H₂O complexes 1-4. These compounds have been characterized by means of IR, mass spectrometry, elemental analysis, NMR and conductimetry, as well as X-ray crystallography for 2 and 3. The [Re(CO)₃]⁺ moiety is coordinated via the nitrogen of the iminodiacetic acid unit and two oxygens of monodentate carboxylate groups. In each case, the nitro group of the aromatic ring remains uncoordinated. The analogous technetium-99m complexes 1′ and 3′ were also prepared quantitatively by the reaction of H₂L¹ and H₂L³, respectively, with the fac-[^99mTc(CO)₃(H₂O)₃]⁺ precursor in ethanol. The corresponding Re and ^99mTc compounds were shown to possess the same structure by means of HPLC studies. The high affinity of these ligands for the Tc(I) or Re(I) core, coupled with the easiness of their derivatization (by reduction of the nitro group in amino group), implies that the utilization of this ligand system to develop target-specific radiopharmaceuticals for diagnosis and therapy is promising.     

Benzimidazole derivatives as NSO ligands for the fac-[M(CO)3] (M = Re, Tc)

Two rhenium(I) tricarbonyl complexes with the tridentate monoanionic NSO ligands, 4-(benzimidazol-2-yl)-3-thiabutanoic acid (complex 3) and [1-(11-carboxyundecanyl)-4-(benzimidazol-2-yl)]-3-thiabutanoic acid (complex 4) were synthesized and characterized by spectroscopic methods and elemental analysis. X-ray crystallographic analysis of complex 3 revealed a distorted octahedral geometry around rhenium defined by the three facially bound CO groups and the NSO donor atom set of the tridentate ligand. The analogous technetium-99m complexes (complexes 5 and 6) were also prepared quantitatively by reaction of the NSO ligands with the fac-[^99mTc(H₂O)₃(CO)₃]⁺ synthon and their identity was established by chromatographic comparison to their rhenium congeners. Biodistribution in mice of complex 6 bearing the fatty acid chain showed significant heart uptake (6.26 ± 0.79% ID/g p.i.) at 1 min accompanied, however, with a heart:blood ratio below 1.     

Influence of the chelator structures on the stability of Re and Tc tricarbonyl complexes with iminodiacetic acid tridentate ligands: a computational study

The development of novel radiopharmaceuticals for nuclear medicine based on M(CO)₃ (M?=?Tc, Re) complexes has attracted great attention. The versatility of this core and the easy production of the fac-[M(CO)₃(H₂O)₃]⁺ precursor could explain this interest. The main characteristics of these tricarbonyl complexes are the high substitution stability of the three CO ligands and the corresponding lability of the coordinated water molecules, yielding, via easy exchange of a variety of bi- and tridentate ligands, complexes xof very high kinetic stability. Here, a computational study of different tricarbonyl complexes of Re(I) and Tc(I) was performed using density functional theory. The solvent effect was simulated using the polarizable continuum model. These structures were used as a starting point to investigate the relative stabilities of tricarbonyl complexes with various tridentate ligands. These complexes included an iminodiacetic acid unit for tridentate coordination to the fac-[M(CO)₃]⁺ moiety (M?=?Re, Tc), an aromatic ring system bearing a functional group (?NO₂, ?NH₂, and –Cl) as a linking site model, and a tethering moiety (a methylene, ethylene, propylene butylene, or pentylene bridge) between the linking and coordinating sites. The optimized complexes showed geometries comparable to those inferred from X-ray data. In general, the Re complexes were more stable than the corresponding Tc complexes. Furthermore, using NH₂ as the functional group, a medium length carbon chain, and ortho substitution increased complex stability. All of the bonds involving the metal center presented a closed shell interaction with dative or covalent character, and the strength of these bonds decreased in the sequence Tc-CO?>?Tc-O?>?Tc-N.     

First example of well-characterized Re and Tc tricarbonyl complexes of ciprofloxacin and norfloxacin in the development of infection-specific imaging agents

Aiming at the development of ^99mTc-based infection-specific imaging agents, the synthesis and characterization of rhenium and technetium-99m tricarbonyl complexes with derivatized ciprofloxacin and norfloxacin is hereby reported. The ligands were prepared by coupling the tridentate chelator picolylamino-N,N-diacetic acid (PADA) with the piperazinyl (NH) nitrogen of ciprofloxacin or norfloxacin, through the employment of the PADA anhydride. The corresponding rhenium complexes were synthesized using the fac-[NEt₄]₂[ReBr₃(CO)₃] precursor and were fully characterized by elemental analysis and NMR spectroscopy. X-ray crystallography of the ciprofloxacin complex showed that the geometry about rhenium is distorted octahedral defined by the NNO donor atom set of the tridentate chelator and the three carbonyl groups. The analogous technetium-99m complexes were prepared quantitatively through the use of the fac-[^99mTc(H₂O)₃(CO)₃]⁺ precursor and their structure was established by comparative HPLC studies using the well-characterized rhenium complexes as reference. Preliminary studies with the technetium-99m complexes showed high bacterial uptake in vitro.     

Synthesis and evaluation of Re/99mTc(I) complexes bearing a somatostatin receptor-targeting antagonist and labeled via a novel [N,S,O] clickable bifunctional chelating agent

The somatostatin receptor subtype 2 (SSTR2) is often highly expressed on neuroendocrine tumors (NETs), making it a popular in vivo target for diagnostic and therapeutic approaches aimed toward management of NETs. In this work, an antagonist peptide (sst₂-ANT) with high affinity for SSTR2 was modified at the N-terminus with a novel [N,S,O] bifunctional chelator (2) designed for tridentate chelation of rhenium(I) and technetium(I) tricarbonyl cores, [Re(CO)₃]⁺ and [^99mTc][Tc(CO)₃]⁺. The chelator-peptide conjugation was performed via a Cu(I)-assisted click reaction of the alkyne-bearing chelator (2) with an azide-functionalized sst₂-ANT peptide (3), to yield NSO-sst₂-ANT (4). Two synthetic methods were used to prepare Re-4 at the macroscopic scale, which differed based on the relative timing of the click conjugation to the [Re(CO)₃]⁺ complexation by 2. The resulting products demonstrated the expected molecular mass and nanomolar in vitro SSTR2 affinity (IC₅₀ values under 30?nM, AR42J cells, [¹²⁵I]iodo-Tyr¹¹-somatostatin-14 radioligand standard). However, a difference in their HPLC retention times suggested a difference in metal coordination modes, which was attributed to a competing N-triazole donor ligand formed during click conjugation. Surprisingly, the radiotracer scale reaction of [^99mTc][Tc(OH₂)₃(CO)₃]⁺ (^99mTc; t_½?=?6?h, 141?keV γ) with 4 formed a third product, distinct from the Re analogues, making this one of the unusual cases in which Re and Tc chemistries are not well matched. Nevertheless, the [^99mTc]Tc-4 product demonstrated excellent in vitro stability to challenges by cysteine and histidine (≥98% intact through 24?h), along with 75% stability in mouse serum through 4?h. In vivo biodistribution and microSPECT/CT imaging studies performed in AR42J tumor-bearing mice revealed improved clearance of this radiotracer in comparison to a similar [^99mTc][Tc(CO)₃]-labeled sst₂-ANT derivative previously studied. Yet despite having adequate tumor uptake at 1?h (4.9% ID/g), tumor uptake was not blocked by co-administration of a receptor-saturating dose of SS-14. Aimed toward realignment of the Re and Tc product structures, future efforts should include distancing the alkyne group from the intended donor atoms of the chelator, to reduce the coordination options available to the [M(CO)₃]⁺ core (M?=?Re, ^99mTc) by disfavoring involvement of the N-triazole.     

Modulation of trans-to-cis photoisomerization and photoluminescence of 1,2-bis(4-pyridyl)ethylene or 4-styrylpyridine coordinated to fac-tricarbonyl(5-chloro-1,10-phenathroline)rhenium(I)

Photochemical and photophysical properties of fac-[Re(CO)₃(Clphen)(trans-L)]⁺ complexes, Clphen = 5-chloro-1,10-phenathroline and L = 1,2-bis(4-pyridyl)ethylene, bpe, or 4-styrylpyridine, stpy, were investigated to complement the understanding of intramolecular energy transfer process in tricarbonyl rhenium(I) complexes having an electron withdrawing group attached to polypyridyl ligands. These new compounds were synthesized, characterized and the photoisomerization quantum yields were accurately determined by ¹H NMR spectroscopy. The true quantum yields for fac-[Re(CO)₃(Clphen)(trans-bpe)]⁺ were constant (Φ = 0.55) at all investigated irradiation wavelengths. However, for fac-[Re(CO)₃(Clphen)(trans-stpy)]⁺, similar true quantum yields were observed only at higher energy irradiation (Φ_{313 nm} = 0.53 and Φ_{365 nm} = 0.57), but it decreased significantly at 404 nm (Φ = 0.41). These results indicated different deactivation pathways for the trans-stpy complex photoisomerization. Quantum yields decreased as the ³IL_trans-L and ³MLCT_Re→NN excited states become closer and the behavior was discussed in terms of the excited state energy gaps. Additionally, luminescence properties of photoproducts, fac-[Re(CO)₃(Clphen)(cis-L)]⁺, were also investigated in different environments to analyze the relative energy of the ³MLCT_Re→Clphen excited state for each compound.     

A new tricarbonyl fac-[M(acac)(isc)(CO)3] complex (M = Re, Tc) with acetylacetonate (acac) and isocyanide (isc) in a 2+1 combination

The synthesis and characterization of the neutral 2+1 mixed ligand complex fac-Re(CO)₃(acac)(isc) (4) with acetylacetonate (acac) as the bidentate ligand and an isocyanide (the isocyanocyclohexane, isc) as the monodentate ligand is described. The synthesis of 4 proceeds through the intermediate formation of the fac-Re(acac)(H₂O)(CO)₃ precursor complex 2. Complex 4 was characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral arrangement of the ligands around Re. At technetium-99m level, the corresponding fac-^99mTc(acac)(isc)(CO)₃ complex 5 was obtained in high yield by reacting the fac-^99mTc(acac)(H₂O)(CO)₃ precursor complex 3 with isocyanocyclohexane and its structure was established by chromatographic comparison with the prototypic rhenium complex using high performance liquid chromatography.     

Synthesis of fac-[Os(CO)3(L)Me2] (L = THF or MeCN) and some reactions with PPh3 and trityl salts

The reaction of cis-[Os(CO)₄Me₂] with Me₃NO in the THF or MeCN yields the complexes fac-[Os(CO)₃(L)Me₂] (where L = THF or MeCN). Whereas the THF complex is unstable and only characterised spectroscopically, fac-[Os(CO)₃(MeCN)Me₂] has been isolated as a white solid and fully characterized by both analytical and spectroscopic methods. These complexes fac-[Os(CO)₃(L)Me₂] are shown to be useful intermediates. Thus, reaction with PPh₃ gives fac-[Os(CO)₃(PPh₃)Me₂] in good yield.Reactions of fac-[Os(CO)₃(L)Me₂] (L = CO or MeCN) with CPh₃PF₆ or B(C₆F₅)₃ have been investigated. Whereas cis-[Os(CO)₄Me₂] showed no reaction with either CPh₃PF₆ or B(C₆F₅)₃, the reaction of fac-[Os(CO)₃(MeCN)Me₂] with CPh₃PF₆ in CH₂Cl₂ occurred over 16 h at room temperature to give an unstable cationic product and CPh₃Me. The reaction was monitored by both IR and NMR spectroscopies. When this reaction of fac-[Os(CO)₃(MeCN)Me₂] was carried out in the presence of a trapping ligand such as MeCN, the stable cationic product [Os(CO)₃(MeCN)₂Me]⁺ could be isolated and identified spectroscopically.     

Synthesis and biological evaluation of tricarbonyl Re(I) and Tc(I) complexes anchored by poly(azolyl)borates: application on the design of radiopharmaceuticals for the targeting of 5-HT<Subscript>1A</Subscript> receptors

The building blocks fac-[^99mTc{κ³-HB(tim^Me)₃}(CO)₃] and fac-[^99mTc{κ³-R(μ-H)B(tim^Me)₂}(CO)₃] [R is H (4a), Ph (5a); tim^Me is 2-mercapto-1-methylimidazolyl] were obtained almost quantitatively by reacting fac-[^99mTc(CO)₃(H₂O)₃]⁺ with the corresponding scorpionate. These compounds cross the intact blood–brain barrier in mice, with significant retention in the case of 4a and 5a. Using 4a as the lead structure, we have synthesized the functionalized complexes fac-[M{κ³-H(μ-H)B(tim^Bu-pip)₂}(CO)₃] [M is Re (8), ^99mTc (8a); tim^Bu-pip is methyl[4-((2-methoxyphenyl)-1-piperazinyl)butyl](2-mercapto-1-methylimidazol-5-yl)methanamide] and fac-[M{κ ³-H(μ-H)B(tim^Me)(tim^Bu-pip)}(CO)₃] [M is Re (9), ^99mTc (9a)] and evaluated their potential as radioactive probes for the targeting of brain 5-HT_1A serotonergic receptors. The Re complexes exhibit excellent affinity [IC₅₀=0.172 ± 0.003 nM (8); IC₅₀=0.65 ± 0.01 nM (9)] for the 5-HT_1A receptor. The radioactive congeners (^99mTc) have shown an initial brain uptake of 1.38 ± 0.46%ID g⁻¹ (8a) and 0.43 ± 0.12%ID g⁻¹ (9a), but suffer from a relatively fast washout.     

Complexes with 6-amino-5-nitroso-2-thiouracil and violuric acid derivatives containing the fac-Re(CO)3 core: Synthesis, XRD structural and photoluminescence characterization

The fac-tricarbonylrhenium(I) complexes of the 6-amino-1,3-dimethyl-5-nitroso-2-thiouracil (DANTU) and violuric acid (VIO) and its mono- (MVIO) and dimethyl (DVIO) derivatives have been prepared. The complexes have been characterized by elemental analysis, IR, ¹H and ¹³C NMR spectral methods and luminescence spectroscopy. The structures of [ReCl(CO)₃(DANTU)], [Re(H₂O)(CO)₃(VIOH₋₁)] and [Re(H₂O)(CO)₃(DVIOH₋₁)] complexes were solved from single-crystal X-ray diffraction experiments. The coordination environment around the Re(I) may be described as a distorted octahedron in which the ligand behaves in a bidentate fashion through the nitrogen atom of the nitroso group and an adjacent carbonylic oxygen, making a five-membered chelate ring. The coordination sphere is completed with three carbonyl groups in fac-arrangement and one chlorine atom (DANTU complex) or water molecule (VIO complexes). The higher acidity of violuric acids, if compared with DANTU one, may explain both synergic deprotonation and chloride substitution in the [ReCl(CO)₃]⁺ moiety to form the Re-violurato complexes.     

Synthesis, characterization and X-ray crystal structure of [Re(L4)(CO)3]Br · 2CH3OH (L4 = N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine): A model compound for novel cationic Tc(I)-tricarbonyl radiotracers useful for heart imaging

This report describes synthesis and evaluation of cationic complexes, [^99mTc(CO)₃(L)]⁺ (L = N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L1), N-[(15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L2) and N-[(18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L3)) as potential radiotracers for heart imaging. Preliminary results from biodistribution studies in female adult BALB-c mice indicated that the cationic ^99mTc(I)-tricarbonyl complex, [^99mTc(CO)₃(L2)]⁺, has a significant localization in the heart at 60 min post-injection. To understand the coordination chemistry of these bisphosphine ligands with the ^99mTc(I)-tricarbonyl core, we prepared [Re(CO)₃(L4)]Br (L4: N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine) as a model compound. [Re(CO)₃(L4)]Br has been characterized by elemental analysis, IR, ESI-MS, NMR (¹H, ¹³C, ¹H-¹H COSY, and ¹H-¹³C HMQC) methods, and X-ray crystallography. In solid state, [Re(CO)₃(L4)]⁺ has a distorted octahedron coordination geometry with PNP occupying one facial plane. The chelator backbone adopts a “chair” conformation with phosphine-P atoms at equatorial positions and the amine-N at the apical site. In solution, [Re(CO)₃(L4)]⁺ is able to maintain its cationic nature with no dissociation of carbonyl ligands or any of the three PNP donors.     

Ultrafast excited-state dynamics of photoisomerizing complexes fac-[Re(Cl)(CO)3(papy)2] and fac-[Re(papy)(CO)3(bpy)] (papy = trans-4-phenylazopyridine)

The character and dynamics of low-lying electronic excited states of the complexes fac-[Re(Cl)(CO)₃(papy)₂] and fac-[Re(papy)(CO)₃(bpy)]⁺ (papy = trans-4-phenylazopyridine) were investigated using stationary (UV-Vis absorption, resonance Raman) and ultrafast time-resolved (visible, IR absorption) spectroscopic methods. Excitation of [Re(Cl)(CO)₃(papy)₂] at 400 nm is directed to ¹ππ^∗(papy) and Re → papy ¹MLCT excited states. Ultrafast (?1.4 ps) intersystem crossing (ISC) to ³nπ^∗(papy) follows. Excitation of [Re(papy)(CO)₃(bpy)]⁺ is directed to ¹ππ^∗(papy), ¹MLCT(papy) and ¹MLCT(bpy). The states ³nπ^∗(papy) and ³MLCT(bpy) are then populated simultaneously in less then 0.8 ps. The ³MLCT(bpy) state decays to ³nπ^∗(papy) with a 3 ps time constant. ³nπ^∗(papy) is the lowest excited state for both complexes. It undergoes vibrational cooling and partial rotation around the -NN- bond, to form an intermediate with a nonplanar papy ligand in less than 40 ps. This species then undergoes ISC to the ground state potential energy surface, on which the trans and cis isomers are formed by reverse and forward intraligand papy rotation, respectively. This process occurs with a time constant of 120 and 100 ps for [Re(Cl)(CO)₃(papy)₂] and [Re(papy)(CO)₃(bpy)]⁺, respectively. It is concluded that coordination of papy to the Re center accelerates the ISC, switching the photochemistry from singlet to triplet excited states. Comparison with analogous 4-styrylpyridine complexes (M. Busby, P. Matousek, M. Towrie, A. Vl?ek Jr., J. Phys. Chem. A 109 (2005) 3000) reveals similarities of the decay mechanism of excited states of Re complexes with ligands containing -NN- and -CC- bonds. Both involve sub-picosecond ISC to triplets, partial rotation around the double bond and slower ISC to the trans or cis ground state. This process is about 200 times faster for the -NN- bonded papy ligand. The intramolecular energy transfer from the ³MLCT-excited ^∗Re(CO)₃(bpy) chromophore to the intraligand state of the axial ligand occurs for both L = stpy and papy with a comparable rate of a few ps.     

Reactions of the fac-[Re(CO)3] and [ReO] moieties with substituted benzothiazoles

The reaction of 2-(2-aminophenyl)benzothiazole (Habt) with [Re(CO)₅Br] led to the isolation of the rhenium(I) complex fac-[Re(Habt)(CO)₃Br] (1). With trans-[ReOCl₃(PPh₃)₂], the ligand Habt decomposed to form the oxofree rhenium(V) complex [Re(itp)₂Cl(PPh₃)] (2) (itp = 2-amidophenylthiolate). From the reaction of trans-[ReOBr₃(PPh₃)₂] with 2-(2-hydroxyphenyl)benzothiazole (Hhpd) the complex [Re^VOBr₂(hpd)(PPh₃)] (3) was obtained. Complexes 1-3 are stable and lipophilic. ¹H NMR and infrared assignments, as well as the X-ray crystal structures, of the complexes are reported.     

A new bisphosphonate-containing <Superscript>99m</Superscript>Tc(I) tricarbonyl complex potentially useful as bone-seeking agent: synthesis and biological evaluation

Aiming to develop new bone-seeking radiotracers based on the organometallic core fac-[^99mTc(CO)₃]⁺ with improved radiochemical and biological properties, we have prepared new conjugates with phosphonate pendant groups. The conjugates comprise a chelating unit for metal coordination, which corresponds to a pyrazolyl-containing backbone (pz) with a N,N,N donor-atom set, and a pendant diethyl phosphonate (pz-MPOEt), phosphonic acid (pz-MPOH) or a bisphosphonic acid (pz-BPOH) group for bone targeting. Reactions of the conjugates with the precursor [^99mTc(H₂O)₃(CO)₃]⁺ yielded (mote than 95%) the single and well-defined radioactive species [^99mTc(CO)₃(κ³-pz-MPOEt)]⁺ (1a), [^99mTc(CO)₃(κ³-pz-MPOH]⁺ (2a) and [^99mTc(CO)₃(κ³-pz-BPOH)]⁺ (3a), which were characterized by reversed-phase high-performance liquid chromatography . The corresponding Re surrogates (1–3), characterized by the usual analytical techniques, including X-ray diffraction analysis in the case of 1, allowed for macroscopic identification of the radioactive conjugates. These radioactive complexes revealed high stability both in vitro (phosphate-buffered saline solution and human plasma) and in vivo, without any measurable decomposition. Biodistribution studies of the complexes in mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion, occurring primarily through the renal–urinary pathway in the case of complex 3a. Despite presenting moderate bone uptake (3.04 ± 0.47% injected dose per gram of organ, 4 h after injection), the high stability presented by 3a and its adequate in vivo pharmacokinetics encourages the search for new ligands with the same chelating unit and different bisphosphonic acid pendant arms.     

Energy transfer pathways in pyridylporphyrin Re(I) adducts

Dimeric and pentameric adducts between a meso-4′ pyridylporphyrin core and either one or four rhenium(I) bipyridine tricarbonyl units, fac-[Re(CO)₃(bipy)(4′MPyP)][CF₃SO₃] and fac-[{Re(CO)₃(bipy)}₄(4′TPyP)][CF₃SO₃]₄(4′MPyP = 4′-monopyridylporphyrin, 4′TPyP = 4′-tetrapyridylporphyrin), respectively, were synthesized and their photophysical behaviors were investigated by emission and absorption time resolved experiments. The adducts exhibit distinctive supramolecular features, different from those of the molecular components. Upon excitation of the core, the typical porphyrin fluorescence is quenched. This effect is attributed to enhanced intersystem crossing in the porphyrin unit, owing to the heavy atom effect provided by the attached rhenium unit(s). Following excitation of rhenium fragments the typical rhenium MLCT emission is not observed while partial sensitization of the porphyrin fluorescence occurs, indicating that fast intercomponent energy and/or electron transfer processes take place in competition with the intersystem crossing in the rhenium unit.     

Efficiency enhancement of the electrocatalytic reduction of CO2: fac-[Re(v-bpy)(CO)3Cl] electropolymerized onto mesoporous TiO2 electrodes

As the greenhouse effect increases, the development of systems able to convert with high efficiency CO₂ to energetically rich molecules owns a crucial weight in the technological and environmental domain. As catalyst, rhenium complexes, of the type fac-[Re(L)(CO)₃Cl] (i.e. L = 2,2′-bipyridyl or 4,4′-bipyridyl), have attracted a large interest demonstrating promising catalytic properties. fac-[Re(v-bpy)(CO)₃Cl]-based polymer deposited onto a solid support has been already investigated as heterogeneous catalyst in the reduction of CO₂. Here, we deposited by electrochemical polymerization fac-[Re(v-bpy)(CO)₃Cl] onto a nanocrystalline TiO₂ film on glass and we investigated by cyclic voltammetry the properties of such heterogeneous catalyst in the electrochemical reduction of CO₂. We demonstrated that the nanoporous nature of the substrate allows to increase the two-dimensional number of redox sites per surface area and hence to get a significant enhancement of the catalytic yield.     

New rhenium complexes with ciprofloxacin as useful models for understanding the properties of [99mTc]-ciprofloxacin radiopharmaceutical

Rhenium complexes with the antibiotic ciprofloxacin have been prepared to be studied as models of technetium radiopharmaceuticals. With this aim, the new rhenium complexes 1 {[ReO(Cpf)₂]Cl}, 2 {[ReO(CpfH)₂]Cl₃} and 3 {fac-[Re(CO)₃(H₂O)(Cpf)]} with ciprofloxacin (CpfH = ciprofloxacin; Cpf = conjugated base of ciprofloxacin) have been synthesised and characterised by elemental analyses, IR, NMR (¹H, ¹⁹F and ¹³C CP-MAS) spectroscopy, as well as MS measurements. All spectroscopic data are consistent with the coordination of ciprofloxacin in all these complexes through the carbonyl and the carboxylate oxygen atoms with the formation of a six member chelate ring.The study of a Tc-ciprofloxacin solution by ESI–MS reveals the presence of [TcO(Cpf)₂]⁺ cations, which agrees with the hypothesis that complexes 1 and 2 can be seen as model rhenium complexes of this radiopharmaceutical.Antimicrobial and DNA gyrase inhibition studies performed with complexes 2 and 3 have shown a very similar behaviour between complex 2 and the free antibiotic, whereas complex 3 exhibit a lower antimicrobial activity.Based on a joint analysis of the data reported in the literature and the chemical and biological results obtained in this study, a tentative proposal to explain some aspects of the behaviour of Tc-ciprofloxacin radiopharmaceutical has been made.     

Non-innocent ligand reservoirs for reducing or oxidizing equivalents in carbonylrhenium(I) complexes: 1,1′-Bis(diphenylphosphino)ferrocene (dppf) and bis-triazinyl-pyridine (BTP)

Organometallic complexes of Re(I) with ligands having opposite redox properties have been synthesized and structurally characterized. X-ray crystal structures of the complexes show typical fac-Re^I(CO)₃ coordination to the redox active ligands. Complete electrochemical and spectroelectrochemical studies on the ligands and the metal complexes were performed. The IR-spectroelectrochemical responses were monitored using the fac-Re(CO)₃ unit as a probe. The 15-20 cm⁻¹ hypsochromic or bathochromic shift of the ν_CO bands upon reduction or oxidation is attributed to ligand-centered processes.     

A new bifunctional amino acid chelator targeting the glucose transporter

The coupling reactions of d-glucosamine, 1,3,4,6-tetra-O-acetylglucosamine, and 4-aminophenyl-galactopyranosine with N,N-bis(quinolinoyl)aminovaleric acid (L1) provided a series of conjugates containing a potentially tridentate donor group terminus linked to a sugar moiety, L2′, L2 and L3, respectively. Reactions of the ligands with [NEt₄]₂[Re(CO)₃Br₃] in refluxing methanol provided the rhenium complexes [Re(CO₃)(L1)]Br (ReL1), [Re(CO)₃(L2)]Br (ReL2), [Re(CO)₃(L2′)]Br (ReL2′) and [Re(CO)₃(L3)]Br (ReL3). The ligands and complexes were characterized by elemental analyses, ¹H and ¹³C NMR, mass spectroscopy and, in the case of L1 and ReL1, by X-ray crystallography. The rhenium complexes exhibit fluorescence emissions with long lifetimes, large Stokes shifts, and moderate quantum yields.