Current interest in the regioselective N-functionalization of tetraazacycloalkanes (cyclen and cyclam) stems mainly from their complexes with radioactive metals for applications in diagnostic (64Cu, 111In, 67Ga) and therapeutic (90Y) medicine, and with paramagnetic ions for magnetic resonance imaging (Gd+3). Selective methods for the N-substitution of cyclen and cyclam is a crucial step in most syntheses of cyclen and cyclam-based radiometal complexes and bifunctional chelating agents. In addition, mixing different pendent groups to give hetero-substituted cyclen derivatives would be advantageous in many applications for fine-tuning the compound's physical properties. So far, numerous approaches for the regioselective N-substitution of tetraazacycloalkanes and more specifically cyclen and cyclam are reported. Unfortunately, none of them are general and every strategy has its own strong points and drawbacks. Herein, we categorize numerous regioselective N-alkylation methods into three strategies, such as 1) direct substitution of the macrocycle, 2) introduction of the functional groups prior to cyclization, and 3) protection/functionalization/deprotection. Our discussion is also split into the methods of mono- and tri-functionalization and di-functionalizataion based on number of substituents. At the end, we describe new trials for the new macrocycles which form more stable metal complexes with various radiometals, and briefly mention the commercially available tetraazacycloalkanes which are used for the biconjugation of biomolecules.
Chelating Agents ; Coordination Complexes ; Cyclization ; Ions ; Ligands* ; Magnetic Resonance Imaging ; Metals

The flavonoid-metal complexes showed obviously stronger bioactivities such as antibiosis, antivirus, anti-inflammatory, anti-tumor and anti-free-radical, possibly because of the stronger binding force caused by the change in complex structure and accessibility to target spots, or the synergy effect between flavonoids and metallic ions. This essay summarizes studies on bioactivity and mechanism of flavonoid-metal complexes, in order to provide reference for in-depth study and development on effective constituents contained in flavonoid traditional Chinese medicines.
Animals ; Coordination Complexes ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Flavonoids ; pharmacology ; Humans ; Medicine, Chinese Traditional

In this paper, the new carbon nanotube modified glassy carbon electrode (F-CNTs/GCE) was prepared to establish a new method for studying the molecular interaction mechanism between baicalin metal complexes (BMC) and bovine serum album (BSA), and the principle of this method was discussed deeply. Under the physiological condition, the thermodynamics and kinetics properties of interaction between BMC and BSA were studied by cyclic voltammetry (CV) to inference their molecular effective mechanism. The results show that the presence of F-CNTs can accelerate the electron transfer, and better response signal was showed in the BMC/BMC-BSA system. The detection of interaction of BMC-BSA used new method show that BMC-BSA generates stable thermodynamically non-covalent compounds, and the obtained average binding sites of BMC-BSA were 1.7; the number of electron transfer in BMC/BMC-BSA reaction process was 2, and non electroactive supramolecular compounds of BMC-BSA were generated by this interacting reaction. The relevant research work provides a new way to study the molecular mechanism for the interaction of drugs with protein, and with a certain reference value for discussion on the non covalent interactions.
Animals ; Cattle ; Coordination Complexes ; chemistry ; Electrodes ; Flavonoids ; chemistry ; Kinetics ; Nanotubes, Carbon ; Serum Albumin, Bovine ; chemistry ; Thermodynamics

Cisplatin is often effective in cancer treatment, but its clinical use is limited because of its nephrotoxicity. We have synthesized new platinum (II) coordination complexes (PC-1 & PC-2) containing trans-l and cis-1, 2-diaminocyclohexane (DACH) as carrier ligands and L-3 -phenyllactic acid (PLA) as a leaving group with the aim of reducing nephrotoxicity but maintaining its anticancer activity. In this study, new platinum (II) complex compounds were evaluated for selective cytotoxicity on cancer cell-lines and normal kidney cells. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human bladder carcinoma cell-lines (T-24/HT-1376). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues, was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be quite less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.
Cisplatin ; Coordination Complexes* ; Glucose ; Humans* ; Kidney* ; Ligands ; Platinum Compounds ; Platinum* ; Urinary Bladder Neoplasms* ; Urinary Bladder*

PURPOSE: The estrogen receptor (ER), which is over-expressed in ER-positive breast tumors, has been imaged by positron emission tomography (PET) using [18F] labeled estrogen ligands, especially [18F]FES. However, [18F] has relatively short-lived half-life (t1/2=1.8 h) and the labeling yield of radio-fluorination is usually low compared with 64Cu (t1/2=12.7 h). 1,4,7,10-tetraazacyclododecane (cyclen) is used to form stable metal complexes with copper, indium, gallium, and gadolinium. With these in mind, we prepared cyclen-based Cu complexes which mimic estradiol in aspect of two hydroxyl groups. MATERIALS AND METHODS: 1,7-Protected cyclen, 1,7-bis (benzyloxycarbonyl)-cyclen was synthesized according to the reported procedure. After introducing two 4-benzyloxybenzyl groups at 4,10-positions, the benzyloxycarbonyl and benzyl groups were removed at the same time by hydrogenation on Pd/C to give 1,7-bis(4-hydroxybenzyl)-1,4,7,10-tetraazacyclododecane (1). RESULTS: The prepared ligand 1 was fully characterized by 1H, 13C NMR, and mass spectrometer. The synthesized ligand was reacted with copper chloride and copper perchlorate to give copper complexes [Cu(1)]2+2(ClO4-) and [Cu(1)Cl]+Cl- which were confirmed by high-resolution mass (FAB). CONCLUSION: We successfully synthesized a cyclen derivative of which two phenol groups are located on trans position of N-atoms. And, two Cu(II) complexes of +2 and +1 overall charge, were prepared as a potential PET tracers for ER imaging.
Breast Neoplasms ; Coordination Complexes ; Copper* ; Estradiol ; Estrogens* ; Gadolinium ; Gallium ; Half-Life ; Hydrogen ; Hydrogenation ; Indium ; Ligands ; Phenol ; Positron-Emission Tomography

We have synthesized new platinum(H) analogs containing 1,2-diaminocyclohexane (dach) as a carrier ligand, 1,3-bis(diphenylphosphino) propane (DPPP) /1,2-bis(diphenylphosphino)ethane (DPPE) as a leaving group and nitrates to improve solubility. In the present study, the cytotoxicity of (Pt(trans-l-dach)(DPPP))cntdot2NO3 (KHPC-001) and (Pt(trans-l-dach)(DPPE)) cntdot 2NO3 (KHPC-002) was evaluated and compared on various P-388 cancer cell lines and porcine kidney cell line (LLC-PK1). The new platinum complexes demonstrated high efficacy on P-388 mouse leukemia cell line as well as cisplatin-resistant (P-388/CDDP) and adriamycin-resistant (P-388/ADR) P-388 cell lines. The intracellular platinum content was measured by a flame atomic absorption spectrophotometer (FAAS), and it was comparable to the results of IC50 of the three complexes on LLC-PK1I and P-388/S cells, while only DPPE compound was accumulated in high volume in P-388/ADR and P-388/CDDP cells. While the DNA-interstrand cross-links of KHPC-001, KHPC-002 and cisplatin were similar on P-388/S leukemia cells, these new platinum complexes were much less DNA cross-linking to a kidney derived cell line, LLC-PK1. These results indicate that KHPC-001 and KHPC-002 are a third-generation platinum complexes with potent antitumor activity and low nephrotoxicity.
Absorption ; Animals ; Cell Line ; Cisplatin ; Coordination Complexes* ; DNA ; Inhibitory Concentration 50 ; Kidney ; Leukemia ; Mice ; Nitrates ; Platinum ; Propane ; Solubility

This study aimed to characterize and MRI track the mesenchymal stem cells labeled with chitosan-coated superparamagnetic iron oxide (Chitosan-SPIO). Chitosan-SPIO was synthesized from a mixture of FeCl2 and FeCl3. The human bone marrow derived mesenchymal stem cells (hBM-MSC) were labeled with 50 microg Fe/mL chitosan-SPIO and Resovist. The labeling efficiency was assessed by iron content, Prussian blue staining, electron microscopy and in vitro MR imaging. The labeled cells were also analyzed for cytotoxicity, phenotype and differentiation potential. Electron microscopic observations and Prussian blue staining revealed 100% of cells were labeled with iron particles. MR imaging was able to detect the labeled MSC successfully. Chitosan-SPIO did not show any cytotoxicity up to 200 microgram Fe/mL concentration. The labeled stem cells did not exhibit any significant alterations in the surface markers expression or adipo/osteo/chondrogenic differentiation potential when compared to unlabeled control cells. After contralateral injection into rabbit ischemic brain, the iron labeled stem cells were tracked by periodical in vivo MR images. The migration of cells was also confirmed by histological studies. The novel chitosan-SPIO enables to label and track MSC for in vivo MRI without cellular alteration.
Animals ; Brain Ischemia/chemically induced/pathology/therapy ; Cell Differentiation ; Chitosan/*chemistry ; Coordination Complexes/*chemistry/toxicity ; Ferric Compounds/*chemistry ; Humans ; Magnetic Resonance Imaging ; Magnetics ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*chemistry/cytology ; Metal Nanoparticles/*chemistry ; Phenotype ; Rabbits

Whole body integrated magnetic resonance imaging (MR)/positron emission tomography (PET) imaging systems have recently become available for clinical use and are currently being used to explore whether the combined anatomic and functional capabilities of MR imaging and the metabolic information of PET provide new insight into disease phenotypes and biology, and provide a better assessment of oncologic diseases at a lower radiation dose than a CT. This review provides an overview of the technical background of combined MR/PET systems, a discussion of the potential advantages and technical challenges of hybrid MR/PET instrumentation, as well as collection of possible solutions. Various early clinical applications of integrated MR/PET are also addressed. Finally, the workflow issues of integrated MR/PET, including maximizing diagnostic information while minimizing acquisition time are discussed.
Coordination Complexes/chemistry/diagnostic use ; Heart/radiography ; Humans ; *Magnetic Resonance Imaging ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplasms/pathology/radiography ; *Positron-Emission Tomography ; Radiopharmaceuticals/diagnostic use ; Tomography, X-Ray Computed ; Whole Body Imaging/*standards/*trends

The complexes of tailor made ligands with life essential metal ions may be an emerging area to answer the problems of multi drug resistance. The coordination complexes of VO(II), Co(II), Ni(II) and Cu(II) with the Schiff bases derived from isatin with 3-chloro-4-floroaniline and 2-pyridinecarboxaldehyde with 4-aminoantipyrine have been synthesized by conventional as well as microwave methods. These compounds have been characterized by elemental analysis, molar conductance, electronic spectra, FT-IR, FAB mass and magnetic susceptibility measurements. FAB mass data show degradation of complexes. Both the ligands behave as bidentate and tridentate coordinating through O and N donor. The complexes exhibit coordination number 4, 5 or 6. The Schiff base and metal complexes show a good activity against the bacteria; Staphylococcus aureus, Escherichia coli and Streptococcus fecalis and fungi Aspergillus niger, Trichoderma polysporum, Candida albicans and Aspergillus flavus. The antimicrobial results also indicate that the metal complexes are better antimicrobial agents as compared to the Schiff bases. The minimum inhibitory concentrations of the metal complexes were found in the range 10~40 microg/mL.
Ampyrone ; Anti-Infective Agents ; Aspergillus flavus ; Aspergillus niger ; Candida albicans ; Coordination Complexes ; Drug Resistance ; Electronics ; Electrons ; Escherichia coli ; Fungi ; Humans ; Ions ; Isatin ; Ligands ; Magnetics ; Magnets ; Microbial Sensitivity Tests ; Microwaves ; Molar ; Pyridines ; Schiff Bases ; Staphylococcus aureus ; Streptococcus ; Tissue Donors ; Trichoderma

Cyclic voltammetric measurements were performed for Co(II), Ni(II), Cu(II) and Zn(II) complexes of 1 : 1 alternating copolymer, poly(3-nitrobenzylidene-1-naphthylamine-co-succinic anhydride) (L) and Ni(II) and Cu(II) complexes of 1 : 1 alternating copolymer, poly(3-nitrobenzylidene-1-naphthylamine-co-methacrylic acid) (L1). The in vitro biological screening effects of the investigated compounds were tested against the fungal species including Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola and Candida albicans and bacterial species including Staphylococcus aureus, Escherichia coli, Klebsiella pneumaniae, Proteus vulgaris and Pseudomonas aeruginosa by well diffusion method. A comparative study of inhibition values of the copolymers and their complexes indicates that the complexes exhibit higher antimicrobial activity. Copper ions are proven to be essential for the growth-inhibitor effect. The extent of inhibition appeared to be strongly dependent on the initial cell density and on the growth medium. The nuclease activity of the above metal complexes were assessed by gel electrophoresis assay and the results show that the copper complexes can cleave pUC18 DNA effectively in presence of hydrogen peroxide compared to other metal complexes. The degradation experiments using Rhodamine B dye indicate that the hydroxyl radical species are involved in the DNA cleavage reactions.
Aspergillus flavus ; Aspergillus niger ; Candida albicans ; Cell Count ; Coordination Complexes ; Copper ; Diffusion ; DNA ; DNA Cleavage ; Electrophoresis ; Escherichia coli ; Hydrogen Peroxide ; Hydroxyl Radical ; Ions ; Klebsiella ; Mass Screening ; Proteus vulgaris ; Pseudomonas aeruginosa ; Rhizoctonia ; Rhizopus ; Rhodamines ; Staphylococcus aureus