Bifunctional Single Amino Acid Chelates for Labeling of Biomolecules with the {Tc(CO)3}+and {Re(CO)3}+Cores. Crystal and Molecular Structures of [ReBr(CO)3(H2NCH2C5H4N)], [Re(CO)3{(C5H4NCH2)2NH}]Br, [Re(CO)3{(C5H4NCH2)2NCH2CO2H}]Br, [Re(CO)3{X(Y)NCH2CO2

Banerjee, Sangeeta Ray; Levadala, Murali K.; Lazarova, Neva; Wei, Lihui; Valliant, John F.; Stephenson, Karin A.; Babich, John W.; Maresca, Kevin P.; Zubieta, Jon

doi:10.1021/ic020476e

Cited by 163 publications

(89 citation statements)

References 53 publications

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“…Peaks related to residual solvents were also identified [21, 22]. Signals related to the dipicolylamine were assigned according to previously reported data of related compounds [5, 23]. Protons attached to the pyridyl nitrogen (H6/6′) are more deshielded and thereby signals are located downfield in the spectrum (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Subasinghe

Perera

Pakhomova

et al. 2016

Bioinorganic Chemistry and Applications

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A novel ligand bearing a central piperidinyl sulfonamide group, N(SO2pip)dpa, and its corresponding Re tricarbonyl complex, [Re(CO)3(N(SO2pip)dpa)]+, have been synthesized in good yield. The methylene CH2 signal seen as a singlet (4.54 ppm) in a 1H NMR spectrum of the ligand in DMSO-d 6 appears as two doublets (5.39, 5.01 ppm) in a spectrum of the [Re(CO)3(N(SO2pip)dpa)]+ complex and confirms the presence of magnetically nonequivalent protons upon coordination to Re. Structural results revealed that the Re–N bond lengths fall within the normal range establishing coordination of ligand to metal. The presence of intraligand π → π ⁎ and n → π ⁎ transitions is indicated by the absorption peaks around 200–250 nm in UV-visible spectra. Absorption peaks in UV-visible spectra around 300 nm for metal complexes were identified as MLCT transitions. The S–N stretch observed as a strong peak at 923 cm−1 for N(SO2pip)dpa appeared at a shorter frequency, at 830 cm−1 in an FTIR spectrum of the [Re(CO)3(N(SO2pip)dpa)]+. The intense fluorescence displayed by the N(SO2pip)dpa ligand has quenched upon coordination to Re. Relatively low IC50 values given by human breast cancer cells, MCF-7, (N(SO2pip)dpa = 139 μM, [Re(CO)3(N(SO2pip)dpa)]+ = 360 μM) indicate that N(SO2pip)dpa and [Re(CO)3(N(SO2pip)dpa)]+ are promising novel compounds that can be further investigated on their usage as potential anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Subasinghe

Perera

Pakhomova

et al. 2016

Bioinorganic Chemistry and Applications

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“…We recently reported a series of compounds, dubbed single amino acid chelates (SAACs), which can be conveniently obtained from commercially available amino acids in a single reaction step either by nucleophilic substitution with 2-chloromethylpydridine (for 27) or reductive amination with pyridine-2-carboxaldehyde and sodium triacetoxyborohydride in dichloroethane (DCE; for 28-31), as illustrated in Scheme 1; these served as building blocks in the synthesis of complexes 47, 48, and 54-58. [34][35][36][37] As a consequence of its low solubility in organic solvents, the direct reductive amination of glycine was not possible under these conditions. Compound 27 was therefore synthesized by nucleophilic substitution according to a published procedure [38] with minor modifications, in 35 % yield.…”

Section: Ligand Synthesesmentioning

confidence: 99%

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Bartholomä¹,

Vortherms²,

Hillier³

et al. 2010

ChemMedChem

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Nucleoside analogues are extensively used in the treatment of cancer and viral diseases. The antiproliferative properties of organorhenium(I) complexes, however, have been scarcely explored to date. Herein we present the syntheses, characterization, and in vitro evaluation of Re(I)(CO)(3) core complexes of thymidine and uridine. For the binding of the Re(I)(CO)(3) core, a tridentate dipicolylamine metal chelate was introduced at positions C5', C2', N3, and C5 with spacers of various lengths. The corresponding organometallic thymidine complexes were fully characterized by IR and NMR spectroscopy and mass spectrometry. Their cytotoxicity was assessed against the A549 lung carcinoma cell line. Toxicity is dependent on the site and mode of conjugation as well as on the nature and the length of the tether. Moderate toxicity was observed for conjugates carrying the rhenium moiety at position C5' or N3 (IC(50)=124-160 microM). No toxicity was observed for complexes modified at C2' or C5. Complex 53, with a dodecylene spacer at C5', exhibits remarkable toxicity and is more potent than cisplatin, with an IC(50) value of 6.0 microM. To the best of our knowledge, this is the first report of the antiproliferative properties of [M(CO)(3)](+1)-nucleoside conjugates. In competitive inhibition experiments with A549 cell lysates and purified recombinant human thymidine kinase 1 (hTK-1), enzyme inhibition was observed for complexes modified at either N3 or C5', but our results suggest that the toxicity cannot be attributed solely to interaction with hTK-1.

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“…30,35 The similarity of the central Re–N bond distances of the analogous [Re(CO) 3 ( N (SO 2 R)dpa)]PF 6 complexes (average = ∼2.277 Å) and in 4 and 6 (average = ∼2.272 Å) indicates that the donating ability of the sulfonamide N is similar for both ligands. 35 Furthermore, all three donor N atoms show good overlap when the C1, C2, C3, and Re atoms in [Re(CO) 3 ( N (SO 2 tol)dien)]PF 6 and [Re(CO) 3 ( N (SO 2 tol)dpa)]PF 6 are superimposed (Figure 3).…”

Section: Resultsmentioning

confidence: 96%

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)₃(N(SO₂R)dien)]PF₆ Complexes with Hydrophilic Sulfonamide Ligands

et al. 2014

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Tertiary sulfonamide nitrogen-to-metal bonds of normal length are very rare. We recently discovered such a bond in one class of fac-[Re(CO)3(N(SO2R)(CH2Z)2)]n complexes (Z = 2-pyridyl) with N(SO2R)dpa ligands derived from di-(2-picolyl)amine (N(H)dpa). fac-[M(CO)3(N(SO2R)(CH2Z)2)]n agents (M = 186/188Re, 99mTc) could find use as radiopharmaceutical bioconjugates when R is a targeting moiety. However, the planar, electron-withdrawing 2-pyridyl groups of N(SO2R)dpa destabilize the ligand to base and create relatively rigid chelate rings, raising the possibility that the rare M– N(sulfonamide) bond is an artifact of a restricted geometry. Also, the hydrophobic 2-pyridyl groups could cause undesirable accumulation in the liver, limiting future use in radiopharmaceuticals. Our goal is to identify a robust, hydrophilic, and flexible N(CH2Z)2 chelate framework. New C2-symmetric ligands, N(SO2R)(CH2Z)2 with (Z = CH2NH2; R = Me, dmb, or tol), were prepared by treating N(H)dien(Boc)2, a protected diethylenetriamine (N(H)dien) derivative, with methanesulfonyl chloride (MeSO2Cl), 3,5-dimethylbenzenesulfonyl chloride (dmbSO2Cl), and 4-methylbenzenesulfonyl chloride (tolSO2Cl). Treatment of fac-[Re(CO)3(H2O)3]+ with these ligands, designated as N(SO2R)dien, afforded new fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes. Comparing the fac-[Re(CO)3(N(SO2Me)dien)]PF6 and fac-[Re(CO)3(N(SO2Me)dpa)]PF6 complexes, we find that the ReI–N(sulfonamide) bonds are normal in length and statistically identical and that the methyl 13C NMR signal has an unusually upfield shift compared to that in the free ligand. We attribute this unusual upfield shift to the fact that the sulfonamide N undergoes an sp2-to-sp3 rehybridization upon coordination to ReI in both complexes. Thus, the sulfonamide N of N(SO2R)dien ligands is a good donor, even though the chelate rings are conformationally flexible. Addition of the strongly basic and potentially monodentate ligand, 4-dimethylaminopyridine, did not affect the fac-[Re(CO)3(N(SO2tol)dien)]PF6 complex, even after several weeks. This complex is also stable to heat in aqueous solution. These results indicate that N(SO2R)dien ligands form fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes sufficiently robust to be utilized for radiopharmaceutical development.

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Cited by 163 publications

References 53 publications

Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)₃(N(SO₂R)dien)]PF₆ Complexes with Hydrophilic Sulfonamide Ligands

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Bifunctional Single Amino Acid Chelates for Labeling of Biomolecules with the {Tc(CO)3}+and {Re(CO)3}+Cores. Crystal and Molecular Structures of [ReBr(CO)3(H2NCH2C5H4N)], [Re(CO)3{(C5H4NCH2)2NH}]Br, [Re(CO)3{(C5H4NCH2)2NCH2CO2H}]Br, [Re(CO)3{X(Y)NCH2CO2

Cited by 163 publications

References 53 publications

Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)3 Thymidine Complexes

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)3(N(SO2R)dien)]PF6 Complexes with Hydrophilic Sulfonamide Ligands

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Product

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Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)₃(N(SO₂R)dien)]PF₆ Complexes with Hydrophilic Sulfonamide Ligands