99mTc bone scanning agents—IV. Chemical characterization of 99mTc(Sn)-pyrophosphate complexes

Various reaction mixtures for the preparation of ⁹⁹Tc(Sn)-pyrophosphate were investigated by means of gel chromatography. All components were radioactively labeled. The most likely composition of the complexes, which also appear in “no carrier added” preparations, was determined.At pH 7 one complex is found with the composition TcPyp₂. Two complexes are found at pH 4: TcPyp and TcPyp₂. Further, at pH 7 a polymeric technetium compound is found not containing tin or pyrophosphate.     

The synthesis of technetium(V) complexes containing sterically bulky thiolate ligands. The molecular structure of tetrabutylammonium oxotetrakis(2,4,6-trimethylbenzenethiolato)technetate(V)

The reactions between [TcOCl₄]⁻ and the sterically bulky thiols ArSH (Ar = 2,4,6-Me₃C₆H₂, 2,4,6- Prⁱ₃C₆H₂ and 2,6-Ph₂C₆H₃) in methanol afford complexes of formula [TcO(SAr)₄]⁻ which may be isolated as salts with bulky organic cations. The molecular structure of [Buⁿ₄N][TcO(2,4,6-Me₃C₆H₂S)₄] was determined by X-ray diffraction methods. The Tc(V) centre was found to adopt the expected square pyramidal geometry in which an oxo group occupies the apical site and the four thiolate sulphurs the basal sites. The TcO distance is 1.659(11) Å and the average TcS distance 2.38(2) Å. The average cis STcS, trans STcS and OTcS angles are respectively 82.7(6)°, 138.4(3)° and 110.8(4)°.     

Preparation,HPLC studies and biological behaviour of 99mTc- and 99mTcN-radiopharmaceuticals based on quinoline type ligands

^99mTc-Complexes of oxine (ox), thiooxine (tox) and 8-hydroxy-5-quinolinesulphonic acid (HQS) were prepared by ligand exchange of ^99mTcNCl₄⁻ and by stannous and dithionite reduction of ^99mTcO₄⁻. HPLC studies showed that the ^99mTcN-tox preparation was almost pure TcN(tox)₂. ^99mTc(Sn)-ox yielded a number of peaks upon HPLC with the major peak being identified as TcO(ox)₂Cl. No other Tc-complexes responsible for other chromatographic peaks were identified. Biodistribution studies in mice showed that all complexes except ^99mTc-HQS were cleared essentially by the hepatobiliary pathway. The ^99mTc-HQS preparations showed increased renal clearance due to the increased aqueous solubility of the complexes resulting from the presence of the sulphonate group on the quinoline ring.     

Light Dependent Reduction of Pertechnetate (TcO(4)) by Broken Chloroplasts

Arguments are given for a ferredoxin-mediated reduction of TcO₄⁻, preponderantly into extractable Tc(V) complexes, by illuminated, broken chloroplasts. Photosynthetic O₂- and NADP-reduction competitively inhibit Tc incorporation. As for O₂, the reaction can be stimulated by the auto-oxidizable electron acceptor methyl viologen. Furthermore TcO₄⁻ can function as terminal acceptor in the diaphorase reaction, with NADPH as electron donor.     

Preparation and evaluation of 99mTc-t-butylisonitrile (99mTc-TBI) for myocardial imaging: a kit for hospital radiopharmacy

A previous method was modified to obtain [^99mTc(TBI)₆]⁺ by reacting Zn(TBI)₂Br₂ directly with ^99mTcO⁻₄ in the presence of Sn²⁺ ions. [Cu(TBI)₄]Cl was next used as a source of TBI. On reaction with ^99mTcO⁻₄ and Sn²⁺ ions for 3 min at 100 °C, [^99mTc(TBI)₆]⁺ product of radiochemical purity >90% and yield >70% was obtained. Data of biodistribution in rats (2–2.5% in heart) and biokinetics in rabbits were satisfactory. The kit formulation was found to be stable and also safe for administration.     

Reactions of the Tridentate and Tetradentate Amine Ligands di-(2-picolyl)(N-ethyl)amine and 2,5-Bis-(2-pyridylmethyl)-2,5 diazohexane with Technetium Nitrosyl Complexes

The reaction of the Tc(II) nitrosyl complex (Bu₄N)[Tc(NO)Cl₄] with di-(2-picolyl)(NEt)amine in methanol yields the neutral complex [Tc(NO)Cl(py-N(Et)-py)]. The reaction of the Tc(I) nitrosyl complex [Tc(NO)Cl₂(HOMe)(PPh₃)₂] with this tridentate ligand yields cationic [Tc(NO)Cl(py-N(Et)-py)(PPh₃)]Cl. These two complexes have been structurally characterized. The reaction of [Tc(NO)Cl₂(HOMe)(PPh₃)₂] with the tetradentate ligand 1,4-bis-(2-pyridylmethyl)-1,4-diazobutane yields a mixture of products including cationic [Tc(NO)Cl(py-NH-NH-py)]Cl and cationic [Tc(NO)Cl(PPh₃)(py-NH-NH∼py)]Cl, with a pyridyl terminus left dangling.     

[TcNBr4−pClp]− (p = 1–3) nitridotechnetate(VI) mixed-ligand complexes. An EPR study

The formation of mixed-ligand complexes of the type [TcNBr_4−pClp]⁻ (p = 1–3) during the reaction between TcNBr₄⁻ and TcNCl₄⁻ is reported. Evidence of the individual mixed-ligand compounds is given by their EPR spectral data. In liquid as well as in frozen solution, a strong dependence of the EPR quantities on the composition of the coordination sphere could be detected. This is shown by a nearly linear dependence of g₀, g∥, a₀^Tc and A∥^Tc on the spin-orbit coupling constants of the equatorial donors.     

The role and mechanism of metal ions and their complexes in enhancing damage in biological systems or in protecting these systems from these systems from the toxicity of O2−

Cooper complexes of 1,10-phenanthroline and some substituted 1,10-phenanthroline cleave DNA in the presence of a reducing agent and molecular oxygen. Generally, the damage is attributed to hydroxyl radicals which are formed through the Haber-Weiss reaction. It is assumed that this reaction occurs with the ternary metal complexes with the biological target and the mechanism is defined as the “site specific mechanism.” In these systems, O₂⁻ drives the cycle through the reduction of copper(II). On the other hand, these same copper complexes catalyze the dismutation of O₂⁻ and thus should protect the systems from O₂⁻ toxicity. In this article, the toxicity of these complexes is explained on kinetic grounds. A general discussion on the various factors which could cause the metal ions or their complexes to act either as protectors from O₂⁻ toxicity or as sensitizers of toxic effects of O₂⁻ is given.     

Effect of Electron Donor and Solution Chemistry on Products of Dissimilatory Reduction of Technetium by Shewanella putrefaciens

To help provide a fundamental basis for use of microbial dissimilatory reduction processes in separating or immobilizing ⁹⁹Tc in waste or groundwaters, the effects of electron donor and the presence of the bicarbonate ion on the rate and extent of pertechnetate ion [Tc(VII)O₄⁻] enzymatic reduction by the subsurface metal-reducing bacterium Shewanella putrefaciens CN32 were determined, and the forms of aqueous and solid-phase reduction products were evaluated through a combination of high-resolution transmission electron microscopy, X-ray absorption spectroscopy, and thermodynamic calculations. When H₂ served as the electron donor, dissolved Tc(VII) was rapidly reduced to amorphous Tc(IV) hydrous oxide, which was largely associated with the cell in unbuffered 0.85% NaCl and with extracellular particulates (0.2 to 0.001 μm) in bicarbonate buffer. Cell-associated Tc was present principally in the periplasm and outside the outer membrane. The reduction rate was much lower when lactate was the electron donor, with extracellular Tc(IV) hydrous oxide the dominant solid-phase reduction product, but in bicarbonate systems much less Tc(IV) was associated directly with the cell and solid-phase Tc(IV) carbonate may have been present. In the presence of carbonate, soluble (<0.001 μm) electronegative, Tc(IV) carbonate complexes were also formed that exceeded Tc(VII)O₄⁻ in electrophoretic mobility. Thermodynamic calculations indicate that the dominant reduced Tc species identified in the experiments would be stable over a range of E_h and pH conditions typical of natural waters. Thus, carbonate complexes may represent an important pathway for Tc transport in anaerobic subsurface environments, where it has generally been assumed that Tc mobility is controlled by low-solubility Tc(IV) hydrous oxide and adsorptive, aqueous Tc(IV) hydrolysis products.     

The kinetics of the anation reaction of aquopentaamminecobalt(III) by acetate in aqueous acidic solution

The anation reaction of aquopentaamminecobalt(III) by acetate has been studied in the temperature range 60–80°C and acidity range 1.0 ≦ pH ≦ 5.5 for total acetate concentrations ≦ 0.5 M and at ionic strength 1.0 M. The anation by acetic acid follows second-order kinetics (k₀), whereas the kinetic results for the anation by acetate (Q₁, k₁) provide evidence for the formation of an ion-pair with the complex ion. Typical experimental results at 70°C are k₀ = 5.33 X 10⁻⁵ M⁻¹ sec⁻¹, Q₁ = 5.87 M⁻¹ and k₁ = 1.46 X 10⁻⁴sec⁻¹. The activation parameters for the different reaction paths are reported and the results discussed with reference to various other anation reactions of Co(III) complexes.     

Synthesis and biological evaluation of new [Tc(N)(PS)]-based mixed-ligand compounds useful in the design of target-specific radiopharmaceuticals: the 2-methoxyphenylpiperazine dithiocarbamate derivatives as an example

This study presents the first application of a general procedure based on the use of the [Tc(N)Cl(PS)(PPh₃)] species (PS is an alkyl phosphinothiolate ligand) for the preparation of Tc(N) target-specific compounds. [Tc(N)Cl(PS)(PPh₃)] selectively reacts with an appropriate dithiocarbamate ligand (S^∧Y) to give [Tc(N)(PS)(S^∧Y)] compounds. 1-(2-Methoxyphenyl)piperazine, which displays a potent and specific affinity for 5HT_1A receptors, was selected as a functional group and conjugated to the dithiocarbamate unit through different spacers (L ⁿ ). [^99mTc(N)(PS)(L ⁿ )] complexes were prepared in high yield (more than 90%). The chemical identity of ^99mTc complexes was determined by high performance liquid chromatography comparison with the corresponding ^99gTc complexes. All complexes were found to be inert toward transchelation with an excess of glutathione and cysteine. No notable biotransformation of the native compound into different species by the in vitro action of the serum and liver enzymes was shown. Nanomolar affinity for the 5HT_1A receptor was obtained for [^99mTc(N)(PSiso)L³] (IC₅₀ = 1.5 nM); a reduction of the affinity was observed for the other complexes as a function of the shortening of the alkyl chain interposed between the dithiocarbamate and the pharmacophore. Negligible brain uptake was found from in vivo distribution data of [^99mTc(N)(PSiso)L³]. The key finding of this study is that the complexes maintained good affinity and selectivity for 5HT_1A receptors, and the IC₅₀ value for [^99gTc(N)(PSiso)L³] being comparable to the IC₅₀ value found for WAY 100635. This result confirmed the possibility of preparing [^99mTc(N)(PS)]-based target-specific compounds without affecting the affinity and selectivity of the bioactive molecules for the corresponding receptors.     

Synthesis and reactivity of binuclear halo-bridge palladium(II) isocyanide complexes

An equimolecular mixture of [Pd(RNC)₂Cl₂] (R = Ph, p-Me C₆H₄) and [Pd(MeCN)₂Cl₂] reacts in boiling, 1,2-dichloroethane to give the binuclear complexes [Pd(RNC)Cl₂]₂.These compounds undergo a variety of bridge-splitting reactions with neutral or anionic ligands yielding complexes of the type cis and trans [Pd(RNC)LX₂] or [Pd(RNC)X₃]⁻ (L = PPh₃, pyridine, C₆H₁₁NC; X = CL, Br).By reaction of [Pd(PhNC)Cl₃]⁻ with MeOH the anionic carbene complex [Pd{C(NHPh)OMe}Cl₃]⁻ is obtained.[Pd(PhNC)Cl₂]₂ reacts with p-toluidine (excess) or o-aminopyridine to give the corresponding mononuclear carbene derivatives.In the case of the mixed derivative [Pd(p-MeC₆H₄NC)(C₆H₁₁NC)Cl₂], only the more activated p-tolylisocyanide was found to react with p-toluidine.The complexes have been characterized by elemental analysis, conductivity measurements, i.r. and ¹H n.m.r. spectra where possible.     

Spectral and photochemical properties of borohydride-treated D1-D2-cytochrome b-559 complex of photosystem II

The D1-D2-cytochrome b-559 reaction center complex of photosystem II with an altered pigment composition was prepared from the original complex by treatment with sodium borohydride (BH⁻₄). The absorption spectra of the modified and original complexes were compared to each other and to the spectra of purified chlorophyll a and pheophytin a (Pheo a) treated with BH⁻₄ in methanolic solution. The results of these comparisons are consistent with the presence in the modified complex of an irreversibly reduced Pheo a molecule, most likely 13¹-deoxo-13¹-hydroxy-Pheo a, replacing one of the two native Pheo a molecules present in the original complex. Similar to the original preparation, the modified complex was capable of a steady-state photoaccumulation of Pheo⁻ and P680⁺. It is concluded that the pheophytin a molecule which undergoes borohydride reduction is not involved in the primary charge separation and seems to represent a previously postulated photochemically inactive Pheo a molecule. The Q_y and Q_x transitions of this molecule were determined to be located at 5°C at 679.5–680 nm and 542 nm, respectively.     

Tin-119 NMR Studies on adduct formation and stereochemistry of organoyltin(IV)trihalides

qazTin-119 and phosphorus-31 NMR spectra have been recorded for a series of adducts of RSnX₃ (R  Me, Ph; X  Cl, Br) with halide, tributylphosphine (P) and tributylphosphine oxide (L). The adducts were either 1:1 five coordinate or 1:2 six coordinate complexes. The tin-ll9 NMR spectra of mixtures of corresponding chloro and bromo complexes reveal, in most cases, all possible mixed halide species but much additional structural information is obtained from these spectra which could not be extracted from the spectra of individual compounds themselves. Thus in some cases, in the five coordinate species the Berry pseudorotation between isomers within a particular stoichiometry could be slowed on the NMR timescale which allowed a determination of the molecular structure. An equimolar mixture of [PhSnCl₅]²⁻ and [PhSnBr₅]²⁻ shows eleven of the twelve geometries possible for [PhSnCl_xBr_5−x]²⁻. In the six coordinate series [RSnX₄P]⁻ the tin-119 NMR spectra of the mixtures of [RSnCl₄P]⁻ and [RSnBr₄P]⁻ allow the geometry to be determined as trans. Application of the pairwise additivity model for calculation of the tin-119 chemical shift positions for the mixed halide systems are discussed.     

Synthesis and evaluation of technetium-99m monocationic mixed ligand complexes of phenyl substituted/condensed tetradentate schiff's bases and trimethylphosphine

Tc-99m monocationic mixed ligand complexes of phenyl substituted/condensed Schiff's bases, N,N′-ethylene-bis-(benzoylacetone imine) (L_b) or N,N′-ethylene-bis-(salicylaldehyde imine) (L_c) or N,N′-ethylene-bis-(2-hydroxyacetophenone imine) (L_d) and trimethylphosphine were synthesized to determine the influence of the presence of a phenyl group in these tracers on their heart uptake in rats. A new formulation procedure using aq. β-hydroxypropylcyclodextrin (HPB) solution was developed for intravenous administration of nonpolar ^99mTc complexes. Comparison of biodistribution data for the reference ^99mTc complex from N,N′-ethylene-bis-(acetylacetone imine) and trimethylphosphine using HPB formulation and alternate formulation (0.9% saline) showed the same results. Biodistribution of the title ^99mTc complexes, [^99mTc L_b (PMe₃)₂]⁺, [^99mTc L_c (PMe₃)₂]⁺ and [^99mTc L_d (PMe₃)₂]⁺ showed heart-to-blood activity ratios of 1.7, 2.1 and 1.7, respectively, at 15 min post-injection in rats.     

Synthesis and spectroscopic studies of platinum(II) complexes of N,N′-dicyclohexylethylenediamine

The platinum(II) complexes of the formula [Pt(DCHEDA)X₂], where DCHEDA is N,N′-dicyclohexylethylenediamine and X⁻ is CL⁻, Br⁻, I⁻, 0.5C₂O₄²⁻ (oxalate), 0.5C₃H₂O₄²⁻ (malonate), 0.5C₉H₄O₆²⁻ (4-carboxyphthalate), 0.5S₂O₃²⁻ or 0.5SO₄²⁻, have been synthesized and characterized by UVVis, IR, and ¹H NMR spectral techniques. All the above complexes are non-electrolytes in DMF/H₂O, except the sulphate complex which becomes a 1:1 electrolyte after incubation for 24 h at 28 °C. The halide complexes were also studied by X-ray photoelectron spectroscopy and these data suggest that there is π-bonding from platinum to halide in these complexes. The oxalate, malonate and sulphate bind in their complexes as bidentate ligands to platinum through two oxygen atoms whereas the thiosulphate in its complex binds as a bidentate ligand to platinum through one oxygen atom and one sulphur atom.     

Synthesis,Characterization, Antimicrobial and Antimalarial Activities of Azines Based Schiff Bases and their Pd(II) Complexes

Herein, we report synthesis, characterization, antimicrobial and antimalarial activities of azines Schiff base ligands (L¹−L⁴) and their palladium (II) complexes ( C¹−C⁴ ) of [Pd(L)(OAc)₂] type. The azine ligands (L¹−L⁴) were prepared by condensation of carbonyl compounds with hydrazine hydrate and their complexes by the reaction of palladium acetate with L¹−L⁴ ligands in 1 : 1 molar ratio. The prepared ligands and their complexes were characterized by spectral characterization using ¹H &¹³C-NMR, FT-IR and mass spectral studies, which revealed that the ligands coordinates via azomethine nitrogen and heteroatom or aryl carbon with palladium. Moreover, Schiff bases and their palladium (II) complexes have been screened for their antibacterial (S. aureus, B. subtillis, and S. typhi, P. aeruginosa), antifungal (C. albicans, A. niger, and A. clavatus) and antimalarial (P. falciparum) activities. The Schiff base L⁴ showed good results for antibacterial against S. aureus (MIC, 50 μg/mL) and antimalarial against P. falciparum (IC₅₀, 0.83 μg/mL). The complex C¹ showed best antibacterial activity (MIC, 62.5 μg/mL) against S. typhi and the complex C⁴ exhibited remarkable antimalarial activity (IC₅₀, 0.42 μg/mL) among the tested compounds. Thus, azines based ligands and their Pd complexes can be good antimicrobial and antimalarial agents if explored further.     

Enhanced hydrolysis of a phosphonate ester by mono-aquo metal cation complexes

The hydrolysis of the ester 2,4-dinitrophenyl- ethyl methylphosphonate has been examined by both stop-flow spectrophotometric and pH-stat techniques. These reactions have been carried out in the presence of several nucleophiles including simple non-labile (w.r.t. substitution) mono-aquo metal ion complexes. Comparison of reaction rates of the metal complexes with sterically hindered organic nucleophiles has led to the conclusion that the metal ions function predominantly as general base catalysts in dilute aqueous solution. Reaction rates for the various nucleophiles studied are tabulated together with solvolysis constants for hydroxide ion and water at 35 °C and I=0.1 mol dm⁻³ (KNO₃). These later two values are respectively 32.7 mol⁻¹ dm³ s⁻¹ and 1.37 x 10⁻⁴ s⁻¹. A Brönsted β value of 0.52 for the phosphonate ester studied has also been derived.     

Mixed ligand complexes of lanthanides with macrocyclic and open-chained polyaminopolycarboxylic acids and acetylacetone

Studies of mixed ligand complex formation stabilities and dissociation kinetics have been performed on lanthanide ions with macrocyclic and open- chained polyaminopolycarboxylic acids (i.e. DAPDA, DACDA, EDDA, and EDTA) and acetylacetone (acac). From UV spectroscopic evidence, it was found that Ln(DACDA)⁺ and Ln(EDTA)⁻ complexes do not form mixed ligand complexes with acac under the set conditions, i.e. pH = 7.2 and complex concentration of 1 x 10⁻⁴ M. On the other hand, formation of Ln(DAPDA)(acac) and Ln(EDDA)(acac)₂⁻ complexes were readily detectable. The mixed complex forma- tion constants,β₁, for the equilibrium Ln(L)⁺ + acac⁻ ⇌ Ln(L)(acac), and β₂, for the equilibrium Ln(L)⁺ + 2 acac⁻ ⇌ Ln(L)(acac)₂⁻ were determined by potentiometric titration technique where possible. It was found that β₁ values were in general greater for Ln(EDDA)⁺ complexes than for Ln(DAPDA)⁺ complexes indicating the resulting reduced charge density at the lanthanide ion of Ln(DAPDA)⁺ and that less space is available for the acetylacetone moiety to coordinate to the Ln(DAPDA)⁺ complexes due to the large size and the greater number of coordination atoms of DAPDA. The hydrolysis constants of Ln(EDDA)(H₂O)_n⁺ species were also determined and were found to be increasing with increasing atomic number of Ln. Attempts to measure the acid assisted mixed ligand complex dissociation rates by a stopped-flow spectrophotometer were not fruitful due to the much faster rates.     

Chromium(III) complexes with 1,5,9-triazanonane (3,3-tri) - CrX3(3,3-tri)n+ and CrCl(diamine)(3,3-tri)2+

The reaction of CrCl₃ · 6H₂O (dehydrated in DMSO) with 1,5,9-triazanonane (3,3-tri) gives mer- CrCl₃(3,3-tri), the configuration being established by isomorphism with the corresponding Co(III) complex. This non-electrolyte is hydrolyzed in aqueous acidic solution and mer-[CrCl₂(3,3-tri)- (OH₂)]ClO₄ can be isolated by anation with HCl in the presence of HClO₄. Reaction of mer-CrCl₃- (3,3-tri) in DMF with diamines produces complexes of the type [CrCl(diamine)(3,3-tri)] Cl₂ [diamine= 1,2-diaminoethane (en), 1.2-diaminopropane (pn), 1,3-diaminopropane (tn), 2,2-dimethyl-1,3-diaminopropane (Me₂tn) and cyclohexanediamine (chxn, cis plus trans mixture; two isomers A and B)] and these have been characterized as the ZnCl₄²⁻ salts. The configuration of the triamine ligand in these complexes has been established as mer-(H↓)- by a single crystal X-ray analysis of [CrCl(en)(3,3-tri)]- ZnCl₄, monoclinic, P2₁, a=7.932, b= 14.711, c= 8.312 Å, β=104.6° and Z=2, refined to a conventional R factor of 0.034. The kinetics of the Hg²⁺- assisted chloride release from [CrCl(diamine)(3,3- tri)]ZnCl₄ salts were measured spectrophotometrically (μ=1.0 M HClO₄ or HNO₃) over 15 K temperature ranges to give, in order, 10⁴k_Hg (298.2 K) (M⁻¹ s⁻¹), E_a(kJ mol⁻¹), ΔS^# (J K⁻¹ mol⁻¹): en- (HClO₄): 5.95, 78.1, -53; pn(HClO₄); 5.24, 81.2; -44; tn(HClO₄): 26.7, 85.6, -15; Me₂tn(HClO₄): 21.8, 78.6, -40; A-chxn(HNO₃): 7.60, 81.0,-41; B-chxn(HNO₃): 18.3, 56.8, -115. A ‘non-replaced ligand effect’ on the rate is observed for the first time in this series of homologous Cr(III) complexes. The kinetics of the thermal aquation (k_H, 0.1 M HClO₄) were measured titrimetrically for CrCl(diamine) (3,3-tri)²⁺ to give the following kinetic parameters: diamine=en: 10⁷ k_H (298.2)=5.34 s⁻¹, E_a=99.2 kJ mol⁻¹, ΔS^#=-40 J K⁻¹ mol^-1; diamine =tn: 10⁷ k_H (298.2)=5.04 s⁻¹, E_a= 82.8, ΔS^#= -96.