174138-01-3

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 4730-54-5 1,4,7-triazacyclononane 
• 86031-24-5 O-(tert-butoxycarbonyl)hydroxylamine 
• 58632-95-4 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile 
• 58966-93-1 1,4,7-triazacyclononane trihydrochloride 
• 52667-89-7 N,N',N-tris(p-toluenesulfonyl)-1,4,7-triazacyclononane 
• 74651-77-7 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile 

Downstream Products

• 214350-91-1 (S)-2-(benzyloxycarbonylamino)-3-(4,7-bis(tert-butoxycarbonyl)-1,4,7-triazonan-1-yl)propanoic acid 
• 340041-92-1 4-(4-nitrobenzyl)oxazolidin-2-one 
• 1005484-24-1 1,4-di-tert-butyl 7-(2-{[(tert-butoxy)carbonyl]amino}-3-(4-nitrophenyl)propyl)-1,4,7-triazonane-1,4-dicarboxylate 
• 1301740-32-8 1-(o-phthalimidoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-35-1 1-(o-aminoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-36-2 1-(m-aminoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-37-3 1-(p-aminoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-38-4 1-{o-[bis(tert-butoxycarbonyl)guanidino]xylyl}-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-39-5 1-{m-[bis(tert-butoxycarbonyl)guanidino]xylyl}-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-40-8 1-{p-[bis(tert-butoxycarbonyl)guanidino]xylyl}-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-33-9 1-(m-phthalimidoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-34-0 1-(p-phthalimidoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-39-5 C₃₅H₅₈N₆O₈ 
• 1372398-21-4 4-bromo-2,6-bis(di-tertbutoxycarbonyl[1,4,7]triazacyclononane-1-yl-methyl)phenol 

Relevant academic research and scientific papers

DNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complex

The dinuclear copper(II) complex [Cu2{bcmp(-H)}(μ-OH)](NO3)2·H2O (1, bcmp = 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol) has been synthesized and characterized by electrospray ionization mass spectrometry, potentiometric titration and cyclovoltammetry. The X-ray structure of the analogous perchlorate salt [Cu2{bcmp(-H)}(μ-OH)](ClO4)2·2.5H2O (2) was determined. Cytotoxicity studies showed very promising activity of 1 against various pancreatic tumor cell lines with IC50 values comparable or even lower than those of cisplatin. The Cu complex displayed low toxicity against a human non-tumor cell line (HEK 293) demonstrating selectivity for cancer cells. 1 converts supercoiled pUC19 plasmid DNA into the nicked form at micromolar concentrations in the absence of added reductants. A detailed kinetic study on the hydrolysis of the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) has been performed. 1 hydrolyses BDNPP with a second order rate constant of 0.047 M s- 1 at pH 8 and 40 °C. Finally, single cell electrophoresis (comet assay) and fluorescence microscopy analysis showed that 1 interacts with cellular DNA and induces apoptotic cell death of Capan-1 pancreatic cancer cells. Western blotting analysis indicated that the Cu complex activates the p53 dependent pathway of apoptosis.

Self-assembly and selective exchange of oligoanions on the surface of monolayer protected Au nanoparticles in water

Self-assembled monolayers on Au nanoparticles terminating with TACN·ZnII head groups are attractive scaffolds for the formation of multivalent supramolecular structures at submicromolar concentrations in water.

Phototoxic activity and DNA interactions of water-soluble porphyrins and their rhenium(I) conjugates

In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one

Phosphodiester cleavage properties of copper(II) complexes of 1,4,7-triazacyclononane ligands bearing single alkyl guanidine pendants

Three new metal-coordinating ligands, L1·4HCl [1-(2-guanidinoethyl)-1,4,7-triazacyclononane tetrahydrochloride], L 2·4HCl [1-(3-guanidinopropyl)-1,4,7-triazacyclononane tetrahydrochloride], and L3·4HCl [1-(4-guanidinobutyl)-1,4,7- triazacyclononane tetrahydrochloride], have been prepared via the selective N-functionalization of 1,4,7-triazacyclononane (tacn) with ethylguanidine, propylguanidine, and butylguanidine pendants, respectively. Reaction of L 1·4HCl with Cu(ClO4)2·6H 2O in basic aqueous solution led to the crystallization of a monohydroxo-bridged binuclear copper(II) complex, [Cu2L 12(μ-OH)](ClO4)3·H 2O (C1), while for L2 and L3, mononuclear complexes of composition [Cu(L2H)Cl2]Cl· (MeOH)0.5· (H2O)0.5 (C2) and [Cu(L 3H)Cl2]Cl· (DMF)0.5· (H 2O)0.5 (C3) were crystallized from methanol and DMF solutions, respectively. X-ray crystallography revealed that in addition to a tacn ring from L1 ligand, each copper(II) center in C1 is coordinated to a neutral guanidine pendant. In contrast, the guanidinium pendants in C2 and C3 are protonated and extend away from the Cu(II)-tacn units. Complex C1 features a single μ-hydroxo bridge between the two copper(II) centers, which mediates strong antiferromagnetic coupling between the metal centers. Complexes C2 and C3 cleave two model phosphodiesters, bis(p-nitrophenyl)phosphate (BNPP) and 2-hydroxypropyl-p-nitrophenylphosphate (HPNPP), more rapidly than C1, which displays similar reactivity to [Cu(tacn)(OH2)2] 2+. All three complexes cleave supercoiled plasmid DNA (pBR 322) at significantly faster rates than the corresponding bis(alkylguanidine) complexes and [Cu(tacn)(OH2)2]2+. The high DNA cleavage rate for C1 {kobs = 1.30 (±0.01) × 10-4 s-1 vs 1.23 (±0.37) × 10-5 s-1 for [Cu(tacn)(OH2)2]2+ and 1.58 (±0.05) × 10-5 s-1 for the corresponding bis(ethylguanidine) analogue} indicates that the coordinated guanidine group in C1 may be displaced to allow for substrate binding/activation. Comparison of the phosphate ester cleavage properties of complexes C1-C3 with those of related complexes suggests some degree of cooperativity between the Cu(II) centers and the guanidinium groups.

TACN-based cationic lipids with amino acid backbone and double tails: Materials for non-viral gene delivery

Cationic lipids have become an efficient type of non-viral vectors for gene delivery. In this Letter, four cationic lipids containing 1,4,7- triazacyclononane (TACN) headgroup, glutamic/aspartic acid backbone and dioleyl tails were designed and synthesize

Phosphate diester cleavage, DNA interaction and cytotoxic activity of a bimetallic bis(1,4,7-triazacyclononane) zinc complex

The dinuclear zinc complex [Zn2{bcmp(-H)}(μ-Cl)](ClO 4)2·H2O {bcmp = 2,6-bis(1,4,7- triazacyclonon-1-ylmethyl)-4-methylphenol} has been synthesized and structurally characterized. The DNA binding affinity was assessed by ethidium bromide fluorescence quenching experiments. The complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration. Mechanistic studies were carried out using the DNA and RNA models bis(2,4-dinitrophenyl) phosphate (BDNPP) and 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). A detailed kinetic analysis suggested that the bridging OH group of the solution species [Zn 2{bcmp(-H)}(μ-OH)]2+ acts as the nucleophile in the hydrolysis of BDNPP, while in the case of HPNP, the bridging OH group acts as a general base and seems to shift to a terminal position upon substrate coordination. Finally, the cytotoxicity profile of the dinuclear zinc(II) complex was assessed. The complex showed promising in vitro antitumour activity against pancreatic and lung cancers cell lines. A new bimetallic Zn complex with a phenolate scaffold ligand with two aza-crown binding sites has been synthesized and characterized. DNA binding, cleavage and cytotoxicity results are reported.

Self-Assembled Multivalent Ag-SR Coordination Polymers with Phosphatase-Like Activity

We show herein the phosphatase-like catalytic activity of coordination polymers obtained after adding Ag+-ions to thiols bearing hydrophobic alkyl chains terminated with a 1,4,7-triazacyclononane (TACN) group. The subsequent addition of Zn2+ -ions to the self-assembled polymers resulted in the formation of multivalent metal coordination polymers capable of catalysing the transphosphorylation of an RNA-model compound (2-hydroxypropyl-4-nitrophenyl phosphate, HPNPP) with high reactivity. Analysis of a series of metal ions showed that the highest catalytic activity was obtained when Ag+-ions were used as the first metal ions to construct the backbone of the coordination polymer through interaction with the -SH group followed by Zn2+-ions as the second metal ions complexed by the TACN-macrocycle. Furthermore, it was demonstrated that the catalytic activity could be modulated by changing the length of the hydrophobic alkyl chain.

Toward supramolecular nanozymes for the photocatalytic activation of Pt(iv) anticancer prodrugs

A supramolecular nanozyme for the photocatalytic conversion of a Pt(iv) anticancer complex to cisplatin is described herein. We employed 1.9 nm Au nanoparticles decorated with thiol ligands bearing a TACN (1,4,7-triazacyclononane) headgroup to encapsulate FMN (riboflavin-5′-phosphate). In the presence of an electron donor, flavin-loaded nanoparticles photocatalyzed the reductive activation of the prodrug cis,cis,trans-[Pt(NH3)2(Cl2)(O2CCH2CH2COOH)2] to cisplatin, achieving turnover frequency values of 7.4 min-1.

Synthesis and evaluation of novel 1,4,7-triazacyclononane derivatives as Cu2+ and Ga3+ chelators

Advances in chelator design are the cornerstone for the development of metals like copper and gallium based biomedical agents and radiopharmaceuticals. To develop optimal chelating ligands, we explored the synthesis and chelating properties of azaheterocycle pendant armed 1,4,7-triazacyclononane (TACN) dimethylcarboxylate derivatives and dimethylphosphonate derivatives. In the complexation kinetics test, dicarboxylate pendant armed TACN derivatives 2,2′-(7-((1H-imidazol-2-yl)methyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-Im), 2,2′-(7-((1-methyl-1H-imidazol-2-yl)methyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-MeIm), and 2,2′-(7-(thiazol-2-ylmethyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-Thia) exhibited fast complexation kinetics towards Cu (II) cations, which were comparable to the frequently explored ligand 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). And the diphosphonate pendant armed TACN derivative ((7-(thiazol-2-ylmethyl)-1,4,7-triazonane-1,4-diyl)bis(methylene))bis(phosphonic acid) (NODP-Thia) bound with Ga (III) cations at a much faster rate than NOTA. Density functional theory studies confirmed that the better complexation kinetics and metal chelating efficiency of NODA-Im, NODA-MeIm, NODA-Thia, and NODP-Thia could be ascribed to the lower Gibbs energies of corresponding chelator-metal complexes than NOTA-metal complexes. The kinetic inertness of the Cu (II) complex with NODA-Im, NODA-MeIm, and NODA-Thia was also demonstrated by cyclic voltammetry studies. Subsequently radiolabeling experiment demonstrated that these metal chelators could efficiently labeled with 64Cu or 68Ga in good radiochemical purities. These preliminary findings support NODA-Im, NODA-MeIm, NODA-Thia, and NODP-Thia as promising leading chelating agents for the development of bifunctional Cu2+ and Ga3+ chelators in biomedical applications.

Design, Synthesis, and Biological Evaluation of Boron-Containing Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a binary therapeutic method for cancer treatment based on the use of a combination of a cancer-specific drug containing boron-10 (10B) and thermal neutron irradiation. For successful BNCT,10B-containing molecules need to accumulate specifically in cancer cells, because destructive effect of the generated heavy particles is limited basically to boron-containing cells. Herein, we report on the design and synthesis of boron compounds that are functionalized with 9-, 12-, and 15-membered macrocyclic polyamines and their Zn2+complexes. Their cytotoxicity, intracellular uptake activity into cancer cells and normal cells, and BNCT effect are also reported. The experimental data suggest that mono- and/or diprotonated forms of metal-free [12]aneN4- and [15]aneN5-type ligands are uptaken into cancer cells, and their complexes with intracellular metals such as Zn2+would induce cell death upon thermal neutron irradiation, possibly via interactions with DNA.