Physicochemical Characterization of Four Gadolinium(III) DTPA‐like Complexes

The analysis of ¹⁷O NMR transverse relaxation rates and EPR transverse electronic relaxation rates for aqueous solutions of the four DTPA‐like (DTPA = diethylenetriamine‐N,N,N′,N″,N″‐pentaacetic acid) complexes, [Gd(DTPA‐PY)(H₂O)]^? (DTPA‐PY = N′‐(2‐pyridylmethyl)), [Gd(DTPA‐HP)(H₂O)₂]^? (DTPA‐HP = N′‐(2‐hydroxypropyl)), [Gd(DTPA‐H1P)(H₂O)₂]^? (DTPA‐H1P = N′‐(2‐hydroxy‐1‐phenylethyl)) and [Gd(DTPA‐H2P)(H₂O)₂] (DTPA‐H2P = N′‐(2‐hydroxy‐2‐phenylethyl)), at various temperatures allows us to understand the water exchange dynamics of these four complexes. The water‐exchange lifetime (τM) parameters for [Gd(DTPA‐PY)(H₂O)]^?, [Gd(DTPA‐HP)(H₂O)₂]^?, [Gd(DTPA‐H1P)(H₂O)₂]^? and [Gd(DTPA‐H2P)(H₂O)₂] are of 585, 98, 163, and 69 ns, respectively. Compared with [Gd(DTPA)(H₂O)]^2? (τM = 303 ns), the τM value of [Gd(DTPA‐PY)(H₂O)]^? is slightly higher, but the other three complexes values are significantly lower than those of [Gd(DTPA)(H₂O)]^2?. This difference is explained by the fact that the gadolinium(III) complexes of DTPA‐HP, DTPA‐H1P, and DTPA‐H2P have two inner‐sphere waters. The ²H longitudinal relaxation rates of the labeled diamagnetic lanthanum complex allow the calculation of its rotational correlation time (τR). The τR values calculated for DTPA‐PY, DTPA‐HP, DTPA‐H1P, and DTPA‐H2P are of 127, 110, 142 and 147 ps, respectively. These four values are higher than the value of [La(DTPA)]^2? (τR = 103 ps), because the rotational correlation time is related to the magnitude of its molecular weight.     

Synthesis and Physicochemical Characterization of New C‐Functionalized Derivatives of the Gadolinium(III) Complex with 3,6,10‐Tris(carboxymethyl)‐3,6,10‐triazadodecanedioic Acid (H5ttda) Exhibiting Fast Water Exchange – Potential Paramagnetic Reporters for Molecular Imaging

To confirm the observation that [Gd(ttda)] derivatives have a significantly shorter residence time τ_M of the coordinated H₂O molecule than [Gd(dtpa)], four new C‐functionalized [Gd(ttda)] complexes, [Gd(4‐Me‐ttda)] ( 1 ), [Gd(4‐Ph‐ttda)] ( 2 ), [Gd(9‐Me‐ttda)] ( 3 ), and [Gd(9‐Ph‐ttda)] ( 4 ), were prepared and characterized (H₅ttda=3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic acid; H₅dtpa=3,6,9‐tris(carboxymethyl)‐3,6,9‐triazaundecanedioic acid). The temperature dependence of the proton relaxivity for these complexes at 0.47 T and of the ¹⁷O transverse relaxation rate of H₂¹⁷O at 7.05 T confirm that the proton relaxivity is not limited by the H₂O‐exchange rate. The residence time of the H₂O molecules in the first coordination sphere of the gadolinium complexes at 310 K, as calculated from ¹⁷O‐NMR data, is 13, 43, 2.9, and 56 ns for 1, 2, 3 , and 4 , respectively. At 310 K, the longitudinal relaxivity of 2 is higher than for the parent compound [Gd(ttda)] and the other complexes of the series. The stability of the new compounds was studied by transmetallation with Zn²⁺ ions. All the new complexes are more stable than the parent compound [Gd(ttda)].     

Synthesis of Two N,N′-bis(N,N-dialkylamide) Derivatives of Diethylenetriaminepentaacetic Acid and the Stabilities of Their Complexes with Gd3+, Ca2+, Cu2+, and Zn2+

Two bis(N,N-dialkylamide) derivatives of DTPA [(carboxymethyl)iminobis (ethylenenitrilo) tetraacetic acid], DTPA-BDMA = the bis(N,N-dimethylamide) and DTPA-BDEA = the bis(N,N-diethylamide) were synthesized. Their protonation constants were determined by potentiometric titration in 0.10 M Me₄NNO₃ and by NMR pH titration at 25.0 ± 0.1 °C. Stability and selectivity constants were measured to evaluate the possibility of using the corresponding gadolinium(III) complexes for magnetic resonance imaging contrast agents. The stability constants of gadolinium(III), copper(II), zinc(II), and calcium(II) complexes with DTPA-BDMA and DTPA-BDEA were investigated quantitatively by potentiometry. The stability constant for gadolinium(III) complexes is larger than those for Ca(II), Zn(II), and Cu(II) complexes. The selectivity constants and modified selectivity constants of the amides for Gd³⁺ over endogenously available metal ions were calculated. Effectiveness of these two ligands in binding divalent and trivalent metal ions in biological media is assessed by comparing pM values at physiological pH 7.4. Spin-lattice relaxivity values R₁ for Gd(III) complexes were also determined. The observed relaxivity values were found to decrease with increasing pH in the acid range below pH 4 and relaxivity values became invariant with respect to pH changes over the range of 4–10. ¹⁷O NMR shifts showed that the [Dy(DTPA-BDMA)] and [Dy(DTPA-BDEA)] complexes had one inner-sphere water molecule. Water proton spin-lattice relaxation rates for the [Gd(DTPA-BDMA)] and [Gd(DTPA-BDEA)] complexes were also consistent with one inner-sphere gadolinium(III) coordination position.     

Synthesis and Characterization of Various Benzyl Diethylenetriaminepentaacetic Acids (dtpa) and Their Paramagnetic Complexes,Potential Contrast Agents for Magnetic Resonance Imaging

Four derivatives of diethylenetriaminepentaacetic acid (=3,6,9‐tris(carboxymethyl)‐3,6,9‐triazaundecanedioic acid (H₅dtpa)), potential contrast agents for magnetic resonance imaging (MRI), carrying benzyl groups at various positions of the parent structure were synthesized and characterized by a thorough multinuclear NMR study, i.e., the (S)‐ and (R)‐stereoisomers 1a and 1b of 4‐benzyl‐3,6,9‐tris(carboxymethyl)‐3,6,9‐triazaundecanedioic acid (H₅[(S)‐(4‐Bz)dtpa] and H₅[(R)‐(4‐Bz)dtpa], the diamide derivative N,N″‐bis[(benzylcarbamoyl)methyl]diethylenetriamine‐N,N′,N″‐triacetic acid (=3,9‐bis[2‐(benzylamino)‐2‐oxoethyl]‐6‐(carboxymethyl)‐3,6,9‐triazaundecanedioic acid; H₃[dtpa(BzA)₂]; 2 ), and the diester derivative N,N″‐bis{[(benzyloxy)carbonyl]methyl}diethylenetriamine‐N,N′,N″‐triacetic acid (=3,9‐bis[2‐(benzyloxy)‐2‐oxoethyl]‐6‐(carboxymethyl)‐3,6,9‐triazaundecanedioic acid; H₃[dtpa(BzE)₂]; 3 ). From the ¹⁷O‐NMR chemical shift of H₂O induced by their dysprosium complexes with ligands 1 – 3 , it was concluded that only one H₂O molecule is contained in the first coordination sphere of these lanthanide complexes. The rotational correlation times (τ_R) of the complexes were estimated from the ²H‐NMR longitudinal relaxation rate of the deuterated diamagnetic lanthanum complexes. The exchange time of the coordinated H₂O molecule (τ_M) was studied through the temperature dependence of the ¹⁷O‐NMR transverse relaxation rate. As compared to [Gd(dtpa)]²⁻, the H₂O‐exchange rate is faster for [Gd{(S)‐(4‐Bz)dtpa}]²⁻ and [Gd{(R)‐(4‐Bz)dtpa}]²⁻‐, slower for [Gd{dtpa(BzA)₂}], and almost identical for [Gd{dtpa(BzE)₂}]. The analysis of the ¹H‐relaxivity of the gadolinium complexes recorded from 0.02 to 300 MHz established that i) the relaxivity of [Gd{dtpa(BzE)₂}] is similar to that of [Gd(dtpa)]²⁻, ii) the slightly slower molecular rotation of [Gd{dtpa(BzA)₂}] induces a mild enhancement of its relaxivity, and iii) the marked increase of relaxivity of [Gd{(S)‐(4‐Bz)dtpa}]²⁻ and [Gd{(R)‐(4‐Bz)dtpa}]²⁻ mainly results from an apparently shorter distance between the gadolinium ion and the H₂O protons of the coordinated H₂O molecule.     

Tris[3‐hydroxy‐2(1 H)‐pyridinonato]‐Komplexe von Al3+, Cr3+ und Fe3+ – Kristall‐ und Molekülstrukturen von 3‐Hydroxy‐2(1 H)‐pyridinon und Tris[3‐hydroxy‐2(1 H)‐pyridinonato]chrom(III)

Tris[3‐hydroxy‐2(1 H)‐pyridinonato] Complexes of Al³⁺, Cr³⁺, and Fe³⁺ – Crystal and Molecular Structures of 3‐Hydroxy‐2(1 H)‐pyridinone and Tris[3‐hydroxy‐2(1 H)‐pyridinonato]chromium(III) Tris[3‐hydroxy‐2(1 H)‐pyridinonato] complexes of Al³⁺, Cr³⁺ and Fe³⁺ are obtained by reactions of 3‐hydroxy‐2(1 H)pyridinone with the hydrates of AlCl₃, CrCl₃ or Fe(NO₃) in aqueous alkaline solutions as polycrystalline precipitates. The compounds are isotypic. X‐ray structure determinations were performed on single crystals of the uncoordinated 3‐hydroxy‐2(1 H)‐pyridinone ( 1 ) (orthorhombic, space group P2₁2₁2₁, a = 405.4(1), b = 683.0(1), c = 1770.3(3) pm, Z = 4) and of the chromium compound 3 (rhombohedral with hexagonal setting, space group R3c, a = 978.1(1), c = 2954.0(1) pm, Z = 6).     

Multiple‐Frequency and Variable‐Temperature EPR Study of Gadolinium(III) Complexes with Polyaminocarboxylates: Analysis and Comparison of the Magnetically Dilute Powder and the Frozen‐Solution Spectra

An electron paramagnetic resonance (EPR) study of glasses and magnetically dilute powders of [Gd(DTPA)(H₂O)]^2?, [Gd(DOTA)(H₂O)]^?, and macromolecular gadolinate(1?) complexes P792 was carried out at the X‐ and Q‐bands and at 240 GHz (DTPA=diethylenetriaminepentaacetato; DOTA=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetato). The results show that the zero‐field splitting (ZFS) parameters for these complexes are quite different in a powder as compared to the frozen aqueous solution. In several complexes, an inversion of the sign of the axial component D of the zero field splitting is observed, indicating a significant structural change. In contrary to what was expected, powder samples obtained by lyophilization do not allow a more precise determination of the static ZFS parameters. The results obtained in glasses are more relevant to the problem of electron spin relaxation in aqueous solution than those obtained from powders.     

Synthesis,Characterization, and DNA‐Binding Properties of the Chiral Ruthenium(II) Complexes Δ‐ and Λ‐[Ru(bpy)2(dmppd)]2+ (dmppd = 10,12‐Dimethylpteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione; bpy = 2,2′‐Bipyridine)

Two novel chiral ruthenium(II) complexes, Δ‐[Ru(bpy)₂(dmppd)]²⁺ and Λ‐[Ru(bpy)₂(dmppd)]²⁺ (dmppd = 10,12‐dimethylpteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione, bpy = 2,2′‐bipyridine), were synthesized and characterized by elemental analysis, ¹H‐NMR and ES‐MS. The DNA‐binding behaviors of both complexes were studied by UV/VIS absorption titration, competitive binding experiments, viscosity measurements, thermal DNA denaturation, and circular‐dichroism spectra. The results indicate that both chiral complexes bind to calf‐thymus DNA in an intercalative mode, and the Δ enantiomer shows larger DNA affinity than the Λ enantiomer does. Theoretical‐calculation studies for the DNA‐binding behaviors of these complexes were carried out by the density‐functional‐theory method. The mechanism involved in the regulating and controlling of the DNA‐binding abilities of the complexes was further explored by the comparative studies of [Ru(bpy)₂(dmppd)]²⁺ and of its parent complex [Ru(bpy)₂(ppd)]²⁺ (ppd = pteridino[6,7‐f] [1,10]phenanthroline‐11,13 (10H,12H)‐dione).     

The Role of Equilibrium and Kinetic Properties in the Dissociation of Gd[DTPA‐bis(methylamide)] (Omniscan) at near to Physiological Conditions

[Gd(DTPA‐BMA)] is the principal constituent of Omniscan, a magnetic resonance imaging (MRI) contrast agent. In body fluids, endogenous ions (Zn²⁺, Cu²⁺, and Ca²⁺) may displace the Gd³⁺. To assess the extent of displacement at equilibrium, the stability constants of DTPA‐BMA^3? complexes of Gd³⁺, Ca²⁺, Zn²⁺, and Cu²⁺ have been determined at 37 °C in 0.15 M NaCl. The order of these stability constants is as follows: GdL≈CuL>ZnL?CaL. Applying a simplified blood plasma model, the extent of dissociation of Omniscan (0.35 mM [Gd(DTPA‐BMA)]) was found to be 17 % by the formation of Gd(PO₄), [Zn(DTPA‐BMA)]^? (2.4 %), [Cu(DTPA‐BMA)]^? (0.2 %), and [Ca(DTPA‐BMA)]^? (17.7 %). By capillary electrophoresis, the formation of [Ca(DTPA‐BMA)]^? has been detected in human serum spiked with [Gd(DTPA‐BMA)] (2.0 mM ) at pH 7.4. Transmetallation reactions between [Gd(DTPA‐BMA)] and Cu²⁺ at 37 °C in the presence of citrate, phosphate, and bicarbonate ions occur by dissociation of the complex assisted by the endogenous ligands. At physiological concentrations of citrate, phosphate, and bicarbonate ions, the half‐life of dissociation of [Gd(DTPA‐BMA)] was calculated to be 9.3 h at pH 7.4. Considering the rates of distribution and dissociation of [Gd(DTPA‐BMA)] in the extracellular space of the body, an open two‐compartment model has been developed, which allows prediction of the extent of dissociation of the Gd^III complex in body fluids depending on the rate of elimination of the contrast agent.     

Dissociation Kinetics of Open‐Chain and Macrocyclic Gadolinium(III)‐Aminopolycarboxylate Complexes Related to Magnetic Resonance Imaging: Catalytic Effect of Endogenous Ligands

The kinetics of the metal exchange reactions between open‐chain Gd(DTPA)^2? and Gd(DTPA‐BMA), macrocyclic Gd(DOTA)^? and Gd(HP‐DO3A) complexes, and Cu²⁺ ions were investigated in the presence of endogenous citrate, phosphate, carbonate and histidinate ligands in the pH range 6–8 in NaCl (0.15 M ) at 25 °C. The rates of the exchange reactions of Gd(DTPA)^2? and Gd(DTPA‐BMA) are independent of the Cu²⁺ concentration in the presence of citrate and the reactions occur via the dissociation of Gd³⁺ complexes catalyzed by the citrate ions. The HCO₃^?/CO₃^2? and H₂PO₄^? ions also catalyze the dissociation of complexes. The rates of the dissociation of Gd(DTPA‐BMA), catalyzed by the endogenous ligands, are about two orders of magnitude higher than those of the Gd(DTPA)^2?. In fact near to physiological conditions the bicarbonate and carbonate ions show the largest catalytic effect, that significantly increase the dissociation rate of Gd(DTPA‐BMA) and make the higher pH values (when the carbonate ion concentration is higher) a risk‐factor for the dissociation of complexes in body fluids. The exchange reactions of Gd(DOTA)^? and Gd(HP‐DO3A) with Cu²⁺ occur through the proton assisted dissociation of complexes in the pH range 3.5–5 and the endogenous ligands do not affect the dissociation rates of complexes. More insights into the interaction scheme between Gd(DTPA‐BMA) and Gd(DTPA)^2? and endogenous ligands have been obtained by acquiring the ¹³C NMR spectra of the corresponding diamagnetic Y(III)‐complexes, indicating the increase of the rates of the intramolecular rearrangements in the presence of carbonate and citrate ions. The herein reported results may have implications in the understanding of the etiology of nephrogenic systemic fibrosis, a rare disease that has been associated to the administration of Gd‐containing agents to patients with impaired renal function.     

Syntheses,characterization and biological studies of zinc(II), copper(II) and cobalt(II) complexes with Schiff base ligand derived from 2‐hydroxy‐1‐naphthaldehyde and selenomethionine

Novel zinc(II), copper(II), and cobalt(II) complexes of the Schiff base derived from 2‐hydroxy‐1‐naphthaldehyde and D, L ‐selenomethionine were synthesized and characterized by elemental analysis, IR, electronic spectra, conductance measurements, magnetic measurements and powder XRD. The analytical data showed the composition of the metal complex to be ML(H₂O), where L is the Schiff base ligand and M = Co(II), Cu(II) and Zn(II). IR results confirmed the tridentate binding of the Schiff base ligand involving azomethine nitrogen, naphthol oxygen and carboxylato oxygen atoms. ¹H NMR spectral data of lithium salt of the Schiff base ligand [Li(HL)] and ZnL(H₂O) agreed with the proposed structures. The conductivity values of complexes between 12.50 and 15.45 S cm² mol^?1 in DMF suggested the presence of non‐electrolyte species. The powder XRD studies indicated that Co(II) complex is amorphous, whereas Cu(II) and Zn(II) complexes are crystalline. The results of antibacterial and antifungal screening studies indicated that Li(HL) and its metal complexes are active, but CuL(H₂O) is most active among them. Copyright © 2010 John Wiley & Sons, Ltd.     

Chloro(η6‐p‐cymene)(phosphoramidite)ruthenium(II), a 16‐Electron Fragment Stabilized by an η2‐Aryl–Metal Interaction,and Its Use in Asymmetric Cyclopropanation

Chloride abstraction from the half‐sandwich complexes [RuCl₂(η⁶‐p‐cymene)(P*‐κP)] ( 2a : P* = (S_a,R,R)‐ 1a = (1S_a)‐[1,1′‐binaphthalene]‐2,2′‐diyl bis[(1R)‐1‐phenylethyl)]phosphoramidite; 2b : P* = (S_a,R,R)‐ 1b = (1S_a)‐[1,1′‐binaphthalene]‐2,2′‐diyl bis[(1R)‐(1‐(1‐naphthalen‐1‐yl)ethyl]phosphoramidite) with (Et₃O)[PF₆] or Tl[PF₆] gives the cationic, 18‐electron complexes dichloro(η⁶‐p‐cymene){(1S_a)‐[1,1′‐binaphthalene]‐2,2′‐diyl {(1R)‐1‐[(1,2‐η)‐phenyl]ethyl}[(1R)‐1‐phenylethyl]phosphoramidite‐κP}ruthenium(II) hexafluorophosphate ( 3a ) and [Ru(S)]‐dichloro(η⁶‐p‐cymene){(1S_a)‐[1,1′‐binaphthalene]‐2,2′‐diyl {(1R)‐1‐[(1,2‐η)‐naphthalen‐1‐yl]ethyl}[(1R)‐1‐(naphthalen‐1‐yl)ethyl]phosphoramidite‐κP)ruthenium(II) hexafluorophosphate ( 3b ), which feature the η²‐coordination of one aryl substituent of the phosphoramidite ligand, as indicated by ¹H‐, ¹³C‐, and ³¹P‐NMR spectroscopy and confirmed by an X‐ray study of 3b . Additionally, the dissociation of p‐cymene from 2a and 3a gives dichloro{(1S_a)‐[1,1′‐binaphthalene]‐2,2′‐diyl [(1R)‐(1‐(η⁶‐phenyl)ethyl][(1R)‐1‐phenylethyl]phosphoramidite‐κP)ruthenium(II) ( 4a ) and di‐μ‐chlorobis{(1S_a)‐[1,1′‐binaphthalene]‐2,2′‐diyl [(1R)‐1‐(η⁶‐phenyl)ethyl][(1R)‐1‐phenylethyl]phosphoramidite‐κP}diruthenium(II) bis(hexafluorophosphate) ( 5a ), respectively, in which one phenyl group of the N‐substituents is η⁶‐coordinated to the Ru‐center. Complexes 3a and 3b catalyze the asymmetric cyclopropanation of α‐methylstyrene with ethyl diazoacetate with up to 86 and 87% ee for the cis‐ and the trans‐isomers, respectively.     

Thermodynamic Stability and Physicochemical Characterization of Ligand (4S)‐4‐Benzyl‐3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic Acid (H5[(S)‐4‐Bz‐ttda]) and Its Complexes Formed with Lanthanides,Calcium(II), Zinc(II), and Copper(II) Ions

A derivative of H₅ttda (=3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic acid=N‐{2‐[bis(carboxymethyl)amino]ethyl}‐N‐{3‐[bis(carboxymethyl)amino]propyl}glycine), H₅[(S)‐4‐Bz‐ttda] (=(4S)‐4‐benzyl‐3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic acid=N‐{(2S)‐2‐[bis(carboxymethyl)amino]‐3‐phenylpropyl}‐N‐{3‐[bis(carboxymethyl)amino]propyl}glycine; 1 ) carrying a benzyl group was synthesized and characterized. The stability constants of the complexes formed with Ca²⁺, Zn²⁺, Cu²⁺, and Gd³⁺ were determined by potentiometric methods at 25.0±0.1° and 0.1M ionic strength in Me₄NNO₃. The observed water proton relaxivity value of [Gd{(S)‐4‐Bz‐ttda}]²⁻ was constant with respect to pH changes over the range pH 4.5–12.0. From the ¹⁷O‐NMR chemical shift of H₂O induced by [Dy{(S)‐4‐Bz‐ttda}]²⁻ at pH 6.80, the presence of 0.9 inner‐sphere water molecules was deduced. The water proton spin‐lattice relaxation rate for [Gd{(S)‐4‐Bz‐ttda}]²⁻ at 37.0±0.1° and 20 MHz was 4.90±0.05 mM ⁻¹ s⁻¹. The EPR transverse electronic relaxation rate and ¹⁷O‐NMR transverse‐relaxation time for the exchange lifetime of the coordinated H₂O molecule (τ_M), and ²H‐NMR longitudinal‐relaxation rate of the deuterated diamagnetic lanthanum complex for the rotational correlation time (τ_R) were thoroughly investigated, and the results were compared with those previously reported for the other lanthanide(III) complexes. The exchange lifetime (τ_M) for [Gd{(S)‐4‐Bz‐ttda}]²⁻ (2.3±1.3 ns) was significantly shorter than that of the [Gd(dtpa)(H₂O)]²⁻ complex (dtpa=diethylenetriaminepentaacetic acid). The rotational correlation time τ_R for [Gd{(S)‐4‐Bz‐ttda}]²⁻ (70±6 ps) was slightly longer than that of the [Gd(dtpa)(H₂O)]²⁻ complex. The marked increase of relaxivity of [Gd{(S)‐4‐Bz‐ttda}]²⁻ mainly resulted from its longer rotational time rather than from its fast water‐exchange rate. The noncovalent interaction between human serum albumin (HSA) and the [Gd{(S)‐4‐Bz‐ttda}]²⁻ complex containing the hydrophobic substituent was investigated by measuring the solvent proton relaxation rate of the aqueous solutions. The association constant (K_A) was less than 100 M ⁻¹, indicating a weaker interaction of [Gd{(S)‐4‐Bz‐ttda}]²⁻ with HSA.     

Koordinativ ungesättigte Dirutheniumkomplexe: Synthese und Kristallstrukturen von [Ru2(CO)3L(μ‐η1 : η2‐C≡CPh)(μ‐PtBu2)(μ‐Ph2PCH2PPh2)] (L = CO,PnBu3)

Coordinatively Unsaturated Diruthenium Complexes: Synthesis and X‐ray Crystal Structures of [Ru₂(CO)₃L(μ‐η¹ : η²‐C≡CPh)(μ‐P^tBu₂)(μ‐Ph₂PCH₂PPh₂)] (L = CO, PⁿBu₃) [Ru₂(CO)₄(μ‐H)(μ‐P^tBu₂)(μ‐dppm)] ( 1 ) reacts with several phosphines (L) in refluxing toluene under substitution of one carbonyl ligand and yields the compounds [Ru₂(CO)₃L(μ‐H)(μ‐P^tBu₂)(μ‐dppm)] (L = PⁿBu₃, 2 a ; L = PCy₂H, 2 b ; L = dppm‐P, 2 c ; dppm = Ph₂PCH₂PPh₂). The reactivity of 1 as well as the activated complexes 2 a – c towards phenylethyne was studied. Thus 1 , 2 a and 2 b , respectively, react with PhC≡CH in refluxing toluene with elimination of dihydrogen to the acetylide‐bridged complexes [Ru₂(CO)₄(μ‐η¹ : η²‐C≡CPh)(μ‐P^tBu₂)(μ‐dppm)] ( 3 ) and [Ru₂(CO)₃L(μ‐η¹ : η²‐C≡CPh)(μ‐P^tBu₂)(μ‐dppm)] ( 4 a and 4 b ). The molecular structures of 3 and 4 a were determined by crystal structure analyses.     

Physicochemical characterization of the dimeric lanthanide complexes [en{Ln(DO3A)(H2O)}2] and [pi{Ln(DTTA)(H2O)}2]2-: a variable-temperature 17O NMR study

The Gd(III) complexes of the two dimeric ligands [en(DO3A)2] {N,N'-bis[1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-10-yl-methylcarbonyl]-N,N'-ethylenediamine} and [pi(DTTA)2]8- [bisdiethylenetriaminepentaacetic acid (trans-1,2-cyclohexanediamine)] were synthesized and characterized. The 17O NMR chemical shift of H2O induced by [en{Dy(DO3A)}2] and [pi{Dy(DTTA)}2]2- at pH 6.80 proved the presence of 2.1 and 2.2 inner-sphere water molecules, respectively. Water proton spin-lattice relaxation rates for [en{Gd(DO3A)(H2O)}2] and [pi{Gd(DTTA)(H2O)}2]2- at 37.0 +/- 0.1 degrees C and 20 MHz are 3.60 +/- 0.05 and 5.25 +/- 0.05 mM(-1) s(-1) per Gd, respectively. The EPR transverse electronic relaxation rate and 17O NMR transverse relaxation time for the exchange lifetime of the coordinated H2O molecule and the 2H NMR longitudinal relaxation rate of the deuterated diamagnetic lanthanum complex for the rotational correlation time were thoroughly investigated, and the results were compared with those reported previously for other lanthanide(III) complexes. The exchange lifetimes for [en{Gd(DO3A)(H2O)}2] (769 +/- 10 ns) and [pi{Gd(DTTA)(H2O)}2]2- (910 +/- 10 ns) are significantly higher than those of [Gd(DOTA)(H2O)]- (243 ns) and [Gd(DTPA)(H2O)]2- (303 ns) complexes. The rotational correlation times for [en{Gd(DO3A)(H2O)}2] (150 +/- 11 ps) and [pi{Gd(DTTA)(H2O)}2]2- (130 +/- 12 ps) are slightly greater than those of [Gd(DOTA)(H2O)]- (77 ps) and [Gd(DTPA)(H2O)]2- (58 ps) complexes. The marked increase in relaxivity (r1) of [en{Gd(DO3A)(H2O)}2] and [pi{Gd(DTTA)(H2O)}2]2- result mainly from their longer rotational correlation time and higher molecular weight.     

Structure and Magnetic Properties of Mononuclear Copper(II) Complexes with 2,2‐Bipyrimidine, 2,3‐Bis(2‐pyridyl)pyrazine,and 4‐Terpyridone Based Ligands

Four new complexes of [Cu(bpm)(ox)(H₂O)] ( 1 ), [Cu(tpd)(dca)(H₂O)] ( 2 ), [Cu(bppz)(N₃)₂] ( 3 ), and [Cu(bpm)₂(μ_1,3‐N₃)(N₃)] ( 4 ) (bpm = 2,2′‐bipyrimidine, bppz = 2,3‐bis(2‐pyridyl)pyrazine, tpd = 4‐terpyridone, dca = dicyanamide, ox = oxalate) have been prepared and characterized by X‐ray single‐crystal analysis and variable‐temperature magnetic measurements. Compounds 1–4 are essentially mononuclear Cu(II) complexes. However, in complex 1 , Cu(II) it was found that intermolecular hydrogen bonding through between H₂O and ox formed 1‐D chain structure. In complex 2 it was found that the hydrogen bonding between H₂O and tpd of the next molecule led to for a binuclear Cu(II) complex. In complex 3 , two nitrogen atoms, one of the pyridyl group of bppz and one of N₃^? ligands, are weakly coordinated to neighbor Cu(II) ion thus leading to formation of a 1‐D chain structure. In complex 4 , one nitrogen atom of terminated N₃^? is weakly coordinated to the neighbor Cu(II) site to form a 1‐D polymeric structure. The magnetic susceptibility measurements indicate that complex 1 and 4 exhibit a weak antiferromagnetic interaction whereas a ferromagnetic coupling has been established for complexes 2 and 3 .     

New insights into water‐soluble and water‐coordinated copper 15‐metallacrown‐5 gadolinium complexes designed for high‐field magnetic resonance imaging applications

The development of contrast agents specifically designed for high‐field magnetic resonance imaging (MRI) is required because the relaxation efficiency of classic Gd(III) contrast agents significantly decreases with increasing magnetic field strengths. With an idea of exploring the unique structure of lanthanide (Ln) 15‐MC‐5 metallacrowns, we developed a series of water‐soluble Gd(III) aqua‐complexes, bearing aminohydroxamate (glycine, α‐alanine, α‐phenylalanine and α‐tyrosine) ligands, with increasing number of water molecules directly coordinated to the Gd(III) ion: Gd(H₂O)₄[15‐MC_Cu(II)Glyha‐5](Cl)₃ ( 1 (Gd)), Gd(H₂O)₄[15‐MC_Cu(II)Alaha‐5](Cl)₃ ( 2 (Gd)), Gd(H₂O)₃[15‐MC_{Cu(II)Phalaha}‐5](Cl)₃ ( 3 (Gd)) and Gd(H₂O)₃[15‐MC_Cu(II)Tyrha‐5](Cl)₃ ( 4 (Gd)). In these systems, the Ln(III) central ion is coordinated by five oxygen donor atoms of the ligands and three or four inner‐sphere water molecules. The X‐ray crystal structure of metallacrown Ln(H₂O)_3,4[15‐MC_Cu(II)Rha‐5]³⁺ agrees with density functional theory predictions. The calculations demonstrate that the exchange of coordinated water molecules can proceed easily, resulting in increased relaxivity parameters. The longitudinal relaxivities (r₁) of 1 (Gd)– 4 (Gd) in water at ultrahigh magnetic field of 9.4 T were determined to be 11.5, 14.8, 13.9 and 12.2 mM^?1 s^?1, respectively. The ability to increase the number of Ln(III) inner‐sphere water molecules up to four, the planar metallacrown structure and the rich hydration shell due to strong hydrogen bonds between the [15‐MC‐5] moiety and bulk water molecules provide new opportunities for potential MRI applications.     

Lanthanide(III) Complexes of 4,10‐Bis(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid (trans‐H6do2a2p) in Solution and in the Solid State: Structural Studies Along the Series

Complexes of 4,10‐bis(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid (trans‐H₆do2a2p, H₆ L ) with transition metal and lanthanide(III) ions were investigated. The stability constant values of the divalent and trivalent metal‐ion complexes are between the corresponding values of H₄dota and H₈dotp complexes, as a consequence of the ligand basicity. The solid‐state structures of the ligand and of nine lanthanide(III) complexes were determined by X‐ray diffraction. All the complexes are present as twisted‐square‐antiprismatic isomers and their structures can be divided into two series. The first one involves nona‐coordinated complexes of the large lanthanide(III) ions (Ce, Nd, Sm) with a coordinated water molecule. In the series of Sm, Eu, Tb, Dy, Er, Yb, the complexes are octa‐coordinated only by the ligand donor atoms and their coordination cages are more irregular. The formation kinetics and the acid‐assisted dissociation of several Ln^III–H₆ L complexes were investigated at different temperatures and compared with analogous data for complexes of other dota‐like ligands. The [Ce( L )(H₂O)]^3? complex is the most kinetically inert among complexes of the investigated lanthanide(III) ions (Ce, Eu, Gd, Yb). Among mixed phosphonate–acetate dota analogues, kinetic inertness of the cerium(III) complexes is increased with a higher number of phosphonate arms in the ligand, whereas the opposite is true for europium(III) complexes. According to the ¹H NMR spectroscopic pseudo‐contact shifts for the Ce–Eu and Tb–Yb series, the solution structures of the complexes reflect the structures of the [Ce(H L )(H₂O)]^2? and [Yb(H L )]^2? anions, respectively, found in the solid state. However, these solution NMR spectroscopic studies showed that there is no unambiguous relation between ³¹P/¹H lanthanide‐induced shift (LIS) values and coordination of water in the complexes; the values rather express a relative position of the central ions between the N₄ and O₄ planes.     

2‐(2′‐Pyridyl)‐4,6‐diphenylphosphinine versus 2‐(2′‐Pyridyl)‐4,6‐diphenylpyridine: Synthesis,Characterization, and Reactivity of Cationic RhIII and IrIII Complexes Based on Aromatic Phosphorus Heterocycles

The bidentate P,N hybrid ligand 1 allows access for the first time to novel cationic phosphinine‐based Rh^III and Ir^III complexes, broadening significantly the scope of low‐coordinate aromatic phosphorus heterocycles for potential applications. The coordination chemistry of 1 towards Rh^III and Ir^III was investigated and compared with the analogous 2,2′‐bipyridine derivative, 2‐(2′‐pyridyl)‐4,6‐diphenylpyridine ( 2 ), which showed significant differences. The molecular structures of [RhCl(Cp*)( 1 )]Cl and [IrCl(Cp*)( 1 )]Cl (Cp*=pentamethylcyclopentadienyl) were determined by means of X‐ray diffraction and confirm the mononuclear nature of the λ³‐phosphinine–Rh^III and Ir^III complexes. In contrast, a different reactivity and coordination behavior was found for the nitrogen analogue 2 , especially towards Rh^III as a bimetallic ion pair [RhCl(Cp*)( 2 )]⁺[RhCl₃(Cp*)]^? is formed rather than a mononuclear coordination compound. [RhCl(Cp*)( 1 )]Cl and [IrCl(Cp*)( 1 )]Cl react with water regio‐ and diastereoselectively at the external P?C double bond, leading exclusively to the anti‐addition products [MCl(Cp*)( 1 H ? OH)]Cl as confirmed by X‐ray crystal‐structure determination.     

Mixed‐Ligand Complexes of Copper(II) with α‐Hydroxycarboxylic Acids and 1,10‐Phenanthroline

Eight new two‐ligand complexes of copper(II) with 1,10‐phenanthroline and one of four different α‐hydroxy‐carboxylic acids (glycolic, lactic, mandelic and benzylic) were prepared. The complexes of general formula [Cu(HL)₂(phen)] · nH₂O (HL = monodeprotonated acid) ( 1 – 4 ) were characterized by elemental analysis, IR, electronic and EPR spectroscopy, magnetic measurements and thermo‐gravimetric analysis. The complexes of general formulae [Cu(HL)(phen)₂](HL) · H₂L · nSolv [ 1 a (HL = HGLYO^–, n = 1, Solv = MeCN) and 3 a (HL = HMANO^–, n = 0)] and [Cu(L)(phen)(OH₂)] · nH₂O [ 2 a (L = LACO^2–, n = 4) and 4 a (L = BENO^2–, n = 2)] were characterized by X‐ray diffractometry. In all these latter a pentacoordinated copper atom has a basically square pyramidal coordination polyhedron, the distortion of which towards a trigonal bipyramidal configuration has been evaluated in terms of the parameter τ. In 1 a and 3 a there are three forms of α‐hydroxycarboxylic acid: a monodentate monoanion, a monoanionic counterion, and a neutral molecule lying in the outer coordination sphere; in 2 a and 4 a the α‐hydroxycarboxylic acid is a bidentate dianion coordinating through carboxyl and hydroxyl oxygens.