Assessment of macrocyclic triamine ligands as synthons for organometallic 99mTc radiopharmaceuticals

In a search of coordination molecules suitable to the fac-{(99m)Tc(CO)3}(+) core as a synthon for (99m)Tc-radiopharmaceuticals, nonradioactive rhenium complexes of two macrocyclic triamine compounds with different chelate ring structures, 1,4,7-triazacyclononane (9N3) and 1,5,9-triazacyclododecane (12N3), were synthesized and characterized. (99m)Tc-labeled 9N3 and 12N3 compounds were also prepared using [(99m)Tc(OH 2)3(CO)3](+) and were characterized by both in vitro and in vivo studies. 9N3 produced a single rhenium complex, whereas 12N3 generated two major complexes. The crystallographic data and infrared absorption wavenumber assigned to the C-O stretch suggested that the coordination geometry of 9N3 would be more suitable to fac-{Re(CO)3}(+) than that of 12N3. In contrast, both 9N3 and 12N3 provided a single (99m)Tc-labeled compound. However (99m)Tc-labeled 9N3 exhibited higher stability than (99m)Tc-labeled 12N3 in rat plasma and in the presence of histidine at an elevated temperature. In biodistribution studies, both (99m)Tc-labeled compounds did not show any specific accumulation of radioactivity in any organs except for the excretory organs such as the liver and kidney. These findings showed that 9N3 would constitute a macrocyclic chelating molecule of choice to prepare (99m)Tc radiopharmaceuticals using a fac-{(99m)Tc(CO)3}(+) core.     

Aqueous synthesis of derivatized cyclopentadienyl complexes of technetium and rhenium directed toward radiopharmaceutical application

Half-sandwich complexes of the type [(RCOCp)M(CO)(3)] with M = Re and (99(m))Tc were synthesized from [M(OH(2))(3)(CO)(3)](+) in water. The R group can be an organic residue or a receptor binding biomolecule with a spacer to cyclopentadienyl (Cp). This provides a general route to Cp complexes of technetium without the need for starting from [TcBr(CO)(5)]. The X-ray structure of [(C(6)H(5)CH(2)COC(5)H(4))Tc(CO)(3)] has been elucidated. The compound crystallizes in the monoclinic space group P2(1)/c with a = 16.1454(9), b = 7.6300(6), and c = 12.3922(7) A and beta = 107.792(6) degrees. We have chosen a serotonergic receptor ligand (WAY) as an example for the derivatization of Cp with a bioactive molecule. WAY is linked to Cp by an aliphatic chain of variable length. The half-sandwich complexes were prepared from water and organic solvents. The structure of [(WAY4-Cp)Re(CO)(3)] could be elucidated. The compound crystallizes in the monoclinic space group P2(1)/c with a = 15.7112(6), b = 6.8775(3), and c = 25.5217(12) A and beta = 103.778(5) degrees. Quantification of inhibition constants gave a clear structure-activity relationship. A single methylene group between the receptor binding site and the half-sandwich complex gave an IC(50) of 217 nM for HT(1A), whereas a butylene linker resulted in retention of the inhibition constant with an IC(50) of 6 nM with respect to underivatized WAY. For use as radiopharmaceuticals, the compounds have also been prepared with (99m)Tc in quantitative yield.     

Determination of99Tc-DPD complex composition and valence states of technetium

DPD (2,3-dicarboxypropane-1,1-diphosphonic acid) forms two complexes with⁹⁹Tc, previously reduced by Sn(II): with _max at 410 nm (pH 3–7), and at 515 nm (pH 5–9.6). By Job's method, formation of complexes with DPD:Tc molar ratios of 21 and 23 was found in acidic medium (pH=3). In order to determine the valence states of Tc in the complex, taking into account that formation of⁹⁹Tc-DPD complex does not occur in absence of a reducing agent (here divalent tin), the redox potentiometric titration method was applied. In acidic medium (pH=3), Tc was reduced to Tc(III) by Sn(II), while in presence of DPD to Tc(IV). In strongly alkaline medium (pH>13) the situation was reverse: Tc(III) was formed in the DPD complex, while Tc(IV) in absence of the ligand. In slightly alkaline medium (pH about 8) in both cases (with or without the ligand) TC(III) was obtained at the titration end point. This phenomenon can explain the dependence of^99mTc-radiopharmaceutical complexes on the sequence of reagent addition. These conclusions are very important for^99mTc-DPD radiopharmaceutical solutions used in diagnostic nuclear medicine for skeletal imaging.     

Crystal and Molecular Structure of Copper(Ⅰ) Complex [Cu(PPh3)2(NO3)]

Mononuclear copper( Ⅰ ) complex [Cu(PPh3)2(NO3)] has been synthesized by ligand reduction of cupric nitrate with PPh3 in methanol and characterized by elemental analyses, molecular weight determination, IR spectra and X-ray single crystal analysis; its molar conductivity has also been measured. The crystal is monoclinic, space group C2/c, a=24.52(5), b=9. 187(2), c=15. 489(3) A; β=116.69 (3)°, V=3118.7(11) A3, Z=4, F(000)=1520, Dc=1.584 g/cm3, R=0.0276,Rw= 0. 0321. The results show that PPh3 coordinates as a monodentate ligand to the Cu( Ⅰ ) atoms, and (NO3) behaves as a bidentate ligand in the prepared complex.     

有机多胺Co(Ⅱ)配合物的合成、晶体结构及抑菌性能

以1-氨乙基哌嗪和丙烯腈为原料合成了新型有机多胺1-(N,N-二氨基丙基)氨基乙基-4-氨基丙基哌嗪,并以此为配体,与高氯酸钴进行配位反应,得到其配合物[Co(L)HCl](ClO4)2的晶体。通过元素分析、摩尔电导率和X射线衍射测试技术对所得晶体进行了分析。结果显示,该晶体结构属四方晶系,空间群I4/m,a=2.5006(3),b=2.5006(3),c=0.85615(11)nm,Mr=594.79,V=5.3534(10)nm3,Z=8,F(000)=2488,Dc=1.476g/cm3,μ(MoKα)=0.989mm-1,最终偏离因子R1=0.0666,wR2=0.1852(I2σ(I))。采用琼脂扩散法测定目标产物的抑菌性能。结果表明,[Co(L)HCl](ClO4)2对金黄色葡萄球菌、大肠杆菌、枯草芽孢杆菌、鳗弧菌均有一定的抑制作用。     

The Crystal Structure of Hexamolybdenum Halide NaMo_6X_9C_（l4）（X＝Cl_n＋I_（1－n）） by Solid State Reaction

ＴｈｅＣｒｙｓｔａｌＳｔｒｕｃｔｕｒｅｏｆＨｅｘａｍｏｌｙｂｄｅｎｕｍＨａｌｉｄｅＮａＭｏ_６Ｘ_９Ｃ_（ｌ４）（Ｘ＝Ｃｌ_ｎ＋Ｉ_（１－ｎ））ｂｙＳｏｌｉｄＳｔａｔｅＲｅａｃｔｉｏｎ￥ＧｕｏＧｕｏ－Ｃｏｎｇ；ＺｈｕａｎｇＨｏｎｇ－Ｈｕｉ；ＷａｎｇＭａｎ?..     

水杨醛-L-缬氨酸合铜(Ⅱ)配合物的合成、晶体结构及热分析研究

X射线单晶结构分析结果表明，深蓝色的水杨醛-L-缬氨酸二吡啶合铜（Ⅱ）配合物晶体-C22H23CuN3O3属单斜晶系，空间群对1114可观测衍射最终一致性因子为R＝0．066，该配合物中心离子是5配位的，其中希夫碱配体提供3个配位原子：N（1）、O（1）、0（2）；另外2个配位原子为2个吹吹分子提供的N（2），N（3）。N（1），N（2），N（3）组成三角形平面与O（1），O（2）构成三角双锥，Cu的配住为畸变三角双锥构型。其中，N（1），N（2），N（3）为赤道配位原子，而O（1）－Cu－O（2）为配合物的轴。     

Synthesis and Crystal Structure of Ni(Ⅱ) Complex with N-Salicylaldehyde-N''''-phenoxyacetylhydrazine Ligand

1INTRODUCTIONHydrazoneshavebeenattractingmuchatten-tionfromchemistsinrecentyearsbecauseoftheirbiologicalactivities,chemicalandindustrialversa-tility,andstrongtendencytochelatetotransitionmetals[1,2],lanthanidemetals[3]andmaingroupmetals[4,5].Inthehydrazonecomplexes,thehydra-zoneligandcanactasaneutralormononegativebidentateligand,orevenasadianionictridentateliganddependingonthedonoratomsoftheligandsandthereactionconditions.Ontheotherhand,variouscompoundsderivedfromphenoxyaceticacidareveryus…     

Synthesis and Crystal Structure of Ni(Ⅱ) Complex with N-Salicylaldehyde-N''-phenoxyacetylhydrazine Ligand

The title complex NiL(py)3, where H2L = N-salicylaldehyde-N'-phenoxyacetyl hydrazine, was prepared and characterized by X-ray diffraction. The single crystal of the title compound, Ni(C15H12N2O3)(C5H5N)3, is of monoclinic, space group P21/c with a = 11.900(1), b = 9.6855(7), c = 23.658(2)A,β = 92.357(2)°, V = 2724.5(4) A3, Z = 4, F(000) = 1176, Dc = 1.376 g/cm3, μ = 0.753 mm-1, R = 0.0332 and Wr = 0.0820. The coordination polyhedron around the nickel atom is an elongated octahedron. The basal plane consists of one phenol oxygen, one amine carbonyl oxygen and one hydrazine nitrogen atoms from the ligand L2- and one nitrogen atom from one coordinated pyridine ligand, while the axial sites are occupied by two nitrogen atoms of two coordinated pyridine ligands.     

Preparation of technetium-99m-humic complex by ligand exchange from hexakis (thiourea-S)technetium(III) complex

The preparation of technetium-99m-humic complex without presence of any metal reductant was studied. For the preparation of Tc-HA complex by ligand substitution hexakis(thiourea-S)technetium(III) complex was used as a precursor. Ligand exchanging reaction was studied with two different humate/thiourea concentration ratios. After mixing of [^99mTc(tu)₆]³⁺ complex with natrium humate under a nitrogen atmosphere a formation of technetium humate wasobserved. The determination of reaction products was performed by combination of gel and paper chromatography. Reaction yields are dependent on humate/thiourea concentration ratio and reaction time. Tc-HA complex was obtained with the highest yield of 62%. Reaction mixture also contains a technetium dioxide as a side product of exchanging reaction and other technetium species, which are also discussed. Oxidation state of technetium in prepared Tc-HA complex is apparently unchanged.     

Synthesis and Structural Characterization of the Complex 〔Et_4N〕_2〔Ni_2(C_2S_4)(C_3S_5)_2〕

１ＩＮＴＲＯＤＵＣＴＩＯＮＴｈｅｃｈｅｍｉｓｔｒｙｏｆｃｏｍｐｏｕｎｄｓｗｉｔｈｄｍｉｔ（ｄｍｉｔ＝１,３ ｄｉｔｈｉｏｌｅ ２ ｔｈｉｏｎｅ ４,５ ｄｉｔｈｉｏｌａｔｅ）ｈａｓａｔｒａｃｔｅｄｃｏｎｓｉｄｅｒａｂｌｅａｔｅｎｔｉｏｎｒｅｃｅｎｔｌ...     

Microwave-assisted synthesis of organometallic complexes of ⁹⁹mTc(CO)₃ and Re(CO)₃: its application to radiopharmaceuticals

(99m)Tc-tricarbonyl [(99m)Tc(CO)(3)] complexes have been conventionally synthesized by heating [(99m)Tc(CO)(3)(H(2)O)(3)](+) and a tridentate chelating ligand under atmospheric pressure; however, this method is poor in terms of chemical yield and reproducibility. Moreover, since the half-life of (99m)Tc is very short (6 h), the development of facile and rapid methods of synthesizing (99m)Tc-labeled compounds, which could be used as radioactive tracers for single photon emission computed tomography (SPECT), is required. Thus, we initiated a study on the application of a microwave reaction to the synthesis of (99m)Tc(CO)(3)-2-picolylamine monoacetic acid (PAMA) [(99m)Tc(CO)(3)-PAMA] complexes on the basis of the fact that synthesis of metal complexes proceeds rapidly by microwave irradiation owing to an efficient exothermic phenomenon and heat conduction effect. Formation of by-products could be markedly suppressed by comparison with that in conventional methods. In the present study, rhenium (Re), an element belonging to the same group in the periodic table as technetium (Tc), and which also forms bipyramidal complexes, was first used to investigate the synthetic reaction because no stable isotopes exist for Tc. As a result, when water was used as the solvent under the irradiation of microwaves within 1 min, the Re(CO)(3)-PAMA complex could be directly synthesized from ethyl ester of PAMA (PAMAEE) and [Re(CO)(3)(H(2)O)(3)]Br in one step and with a high yield (94%). Finally, the (99m)Tc(CO)(3)-PAMA complex was successfully synthesized at a high radiochemical yield (>99%) within 1 min of reaction using (99m)Tc instead of Re under the same conditions.     

Crystal and Molecular Structure of Copper(Ⅰ) Complex 〔Cu(PPh_3)_2(NO_3)〕

1　 INTRODUCTIONCopper( ) displays a wide diversity in its structural chemistry,the copper co-ordination number ranging from two to four.Procedures to synthesize copper( )complexes are of greatinterestbecause of the diversity of products resulting from al-mostthe same methodology.Ithaslong been accepted thatcopper( ) complexesarediamagnetic and provide no optical absorption bands( no d- d transition isencountered) for a copper( ) ion with a d10 configuration and no electron spin reso-n…     

Synthesis and Structure of the Copper(Ⅰ) Complex [Cu(PPh3)2(BH4)]

Mononuclear copper( Ⅰ ) complex [Cu(PPh3)2(BH4)] has been synthesized by ligand replacement reaction in methanol and characterized by elemental analyses, molecular weight determination, IR spectra and X-ray single crystal analysis,its conductivity has also been measured. The crystal is monoclinic, space group C2/c, a =24.776(4), b=9.173(7), c=15.564(2)A; β=116.10(1)°, V=3176.73 A3, Z =4, F(000)=1256, μ(MoKα)=8.11 cm-1, Dc=1. 26 g/cm3, M=602.79, R=0. 039, Rw= 0. 050. The results show that PPh3 coordinates as monodentate ligand to the Cu ( Ⅰ ) atoms, and BH4 behaves as a bidentate ligand in the prepared complex.The central copper atom belongs to tetrahedron coordination geometry.     

Syntheses and characterization of dicarbonyl-nitrosyl complexes of technetium(I) and rhenium(I) in aqueous media: spectroscopic, structural, and DFT analyses

This work describes new synthetic routes to produce mixed carbonyl-nitrosyl complexes of technetium(I) and rhenium(I) in aqueous media. NaNO2, NOHSO4, and NO2(g) have been used to produce in situ nitrous acid as the primary source of NO+. Starting from the organometallic precursor fac-[MX3(CO)3]+, 1 (M = 99Tc, Re; X = Cl, Br), the formation of mixed dicarbonyl-mononitrosyl complexes was observed in aqueous hydrochloric and hydrobromic acid. Time-dependent analyses of the reactions by means of HATR-IR and 99Tc NMR spectroscopy in solution revealed the almost quantitative substitution of one CO ligand by NO+ and, thus, the formation of complexes with facial arrangement of the three pi-acceptor ligands. In the case of technetium, the monomeric complex (NEt4)[TcCl3(CO)2NO] (3a) and the dimeric, chloride-bridged, neutral complex [TcCl(mu-Cl)(CO)2NO]2 (4a) were produced. In the case of rhenium, the monomeric species (NEt4)[ReBr2X(CO)2NO] (X = Br (3b), NO3 (5)) was solely isolated. The X-ray structure of complexes 4a and 5 are discussed. The crystallographic analyses revealed the coordination of the NO+ group trans to the terminal chloride (4a) or the bromide (5), respectively. Crystal data: complex 4a (C4Cl4N2O(6)Tc2), monoclinic, Cc, a = 18.82(3) A, b = 6.103(6) A, c = 12.15(2) A, alpha = 90 degrees , beta = 105.8(2) degrees , gamma = 90 degrees , V = 1343(3) A(3), Z = 4; complex 5 (C10H20N3O(6)Br2Re), orthorhombic, P2(1)2(1)2(1), a = 10.2054(5) A, b = 12.5317(7) A, c = 13.9781(7) A, V = 1787.67(16) A(3), Z = 4. The isolated complexes and their potential facial isomers have been further investigated by density functional theory (DFT) calculations. The energy differences of the isomers are relatively small; however, the calculated energies are consistent with the formation of the observed and isolated compounds. The calculated bond lengths and angles of complex 5 are in good agreement with the data determined by X-ray diffraction. Experiments on the no-carrier-added level starting from fac-[99mTc(H2O)3(CO)3]+ revealed the formation of the complex fac-[99mTcCl(H2O)2(CO)2NO]+ in reasonable good yields. This aqueous-based, synthetic approach will enable the future evaluation of this novel, low-valent metal precursor for potential use in radiopharmacy.     

Synthesis and characterization of novel oxotechnetium (99Tc and 99mTc) and oxorhenium complexes from the 2,2'-bipyridine (NN)/thiol (S) mixed-ligand system

The synthesis and characterization of oxotechnetium and oxorhenium mixed-ligand complexes of the general formula MO[NN][S](3) (M = (99)Tc and Re), where NN represents the bidentate ligand 2,2'-bipyridine and S represents a monodentate thiophenol, is reported. The complexes were prepared by ligand exchange reactions using (99)Tc-gluconate and ReOCl(3)(PPh(3))(2) as precursors for the oxotechnetium and oxorhenium complexes, respectively. Compound 1 (M = (99)Tc, S = 4-methylthiophenol) crystallizes in the monoclinic space group P2(1)/a, a = 23.12(1) A, b = 14.349(6) A, c = 8.801(4) A, beta = 94.81(2) degrees, V = 2918(2) A(3), Z = 4. Compound 3 (M = Re, S = 4-methylthiophenol) crystallizes in the monoclinic space group P2(1)/a, a = 23.018(9) A, b = 14.421(5) A, c = 8.775(3) A, beta = 94.78(1) degrees, V = 2903(2) A(3), Z = 4. Compound 4 (M = Re, S = 4-methoxythiophenol) crystallizes in the orthorhombic space group Pbca, a = 16.32(1) A, b = 24.55(2) A, c = 16.94(1) A, V = 6788(9) A(3), Z = 8. In all cases, the coordination geometry around the metal is distorted octahedral with the equatorial plane being defined by the three sulfur atoms of the thiophenols and one nitrogen atom of 2,2'-bipyridine, while the apical positions are occupied by the second nitrogen atom of 2,2'-bipyridine and the oxygen of the M=O core. The complexes are stable, neutral, and lipophilic. Complete (1)H and (13)C NMR assignments are reported for all complexes. The analogous oxotechnetium complexes have been also synthesized at tracer level ((99m)Tc) by mixing the 2,2'-bipyridine and the corresponding thiol with Na(99m)TcO(4) generator eluate using NaBH(4) as reducing agent. Their structure was established by chromatographic comparison with authentic oxotechnetium and oxorhenium complexes using high performance liquid chromatography techniques.     

Synthesis and Structure of the Copper(Ⅰ) Complex 〔Cu(PPh_3)_2(BH_4)〕

1　INTRODUCTIONCopper( ) displayswide diversity in itsstructuralchemistry,the copper coor dination number ranging from two to four.Procedures to synthesize copper( )complexes itself are of great interest because of the diversity of products resultingfrom almost the same methodology.Ithas long been accepted that because copper( ) complexesare diamagnetic,and hence,provideno opticalabsorption bands( nod d transition is encountered) for a copper( ) ion with a d10 configuration and noelect…     

含双二苯基膦乙烷镍配合物的合成与性质

在氯访中通过取代反应制备了含双二苯基膦乙烷（ｄｐｐｅ）的镍配合物［Ｎｉ（ｄｐｐｅ）Ｃｌ_２］,并通过元素分析、热分析、红外光谱、核磁、电导测定、光电子能谱及Ｘ－射线单晶分析表征了配合物的结构和性质,晶体属于单斜品系,空间群为ｐ２_１／ｃ。晶胞参数如下：ａ＝１１．４２９（２）,ｂ＝１３．３４６（２）,ｃ二１５．９５３（７）Ａ;β＝９９．１３（３）°,Ｖ＝２４０２．５Ａ~３, Ｚ＝４, Ｆ（０００）＝１０８８, Ｄ_（ｃａｌｃ）＝１４６０９· ｃｍ~（－３）, ｐ＝１１．７８２ｃｍ~（－１）, Ｒ＝０．０４４７０, Ｒｗ＝０．０５３５２。分析结果表明,配合物中双二苯基膦乙烷属双齿配体,氯离子是单齿配体．     

Synthesis and Crystal Structure of a Copper(II) Complex with α-Hydroxylated Acid, [Cu(C_(14)H_8O_3)(C_5H_(13)NO)(H_2O)].0.5H_2O

1 INTRODUCTION There has been considerable interest of copper(II) -hydroxylate complexes in the structural chemistry and biochemistry. There are two structural types in copper(II) -hydroxylate com- plexes: mononuclear[1~6] and dinuclear structure[7~9]. The present work is a part of our study on the copper complexes of -hydroxylated acid and reports the synthesis and structure of a mononuclear copper(II) complex with 9-hydroxy- fluorene-9-carboxylato acid, [Cu(C14H8O3)(C5H13- NO)(H…     

Synthesis and Crystal Structure of cis—[meso—1,3—Bis（propylsulfinyl）propane]dichloroplatinum（Ⅱ）

1 INTRODUCTION A number of Pt complexes with monosulfoxide have been isolated and characterized[1]. It was indicated that the sulfoxide group trends to coordinate to soft metals (Pt, Pd, etc.) by its sulfur atom[2]. Pt(Ⅱ) trends to bond to disulfoxides in cis-mode and such complexes have potential antitumor activity[2]. However, only few examples of such complexes have been structurally characterized[3]. We will report herein the crystal structure of a new Pt(Ⅱ) complex with a disulf…