Bioconcentration, metabolism and neurotoxicity of the organophorous flame retardant 1,3-dichloro 2-propyl phosphate (TDCPP) to zebrafish.

Organophosphate flame retardants are ubiquitous environmental contaminants; however, knowledge is limited regarding their environmental health risks and toxicity. Here, we investigated the effects of acute and long-term exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCPP) to the nervous system of zebrafish. Zebrafish embryos (2 h post-fertilization) were exposed to TDCPP (0-100 µg/L) for 6 months up until sexual maturation. Concentrations of TDCPP and its metabolic product (bis(1,3-dichloro-2-propyl) phosphate, BDCPP) were measured in the tissues of 5 day post-fertilization (dpf) larvae. There was no effect on locomotion, acetylcholinesterase activity, levels of the neurotransmitters dopamine and serotonin, and expression of mRNAs and proteins related to central nervous system development (e.g., myelin basic protein, α1-tubulin) in any exposure group. However, in adult fish, reductions of dopamine and serotonin levels were detected in the brains of females but not males. Downregulation of nervous system development genes was observed in both the male and female brain tissues. TDCPP concentrations were measured in adult fish tissues including the brain, and greater levels were detected in females. Our results showed that females are more sensitive to TDCPP stress than males in terms of TDCPP-induced neurotoxicity. We demonstrate that long-term exposure to lower concentrations of TDCPP in fish can lead to neurotoxicity.

Design of luminescent biotinylation reagents derived from cyclometalated iridium(III) and rhodium(III) bis(pyridylbenzaldehyde) complexes.

A new class of luminescent biotinylation reagents derived from cyclometalated iridium(III) and rhodium(III) bis(pyridylbenzaldehyde) biotin complexes, [Ir(pba)(2)(bpy-C6-biotin)](PF(6)) (1), [Ir(pba)(2)(bpy-TEG-biotin)](PF(6)) (2), and [Rh(pba)(2)(bpy-C6-biotin)](PF(6)) (3), together with their biotin-free counterparts [Ir(pba)(2)(bpy-Et)](PF(6)) (4) and [Rh(pba)(2)(bpy-Et)](PF(6)) (5) [Hpba = 4-(2-pyridyl)benzaldehyde, bpy-C6-biotin = 4-[(6-biotinamido)hexylaminocarbonyl]-4'-methyl-2,2'-bipyridine, bpy-TEG-biotin = 4-[(13-biotinamido-4,7,10-trioxa)tridecylaminocarbonyl]-4'-methyl-2,2'-bipyridine, bpy-Et = 4-(ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine], have been synthesized and characterized and their photophysical and electrochemical properties studied. Upon photoexcitation, the iridium(III) complexes 1, 2, and 4 exhibited intense and long-lived orange-yellow luminescence in fluid solutions at 298 K and in rigid glass at 77 K. The rhodium(III) complexes 3 and 5 were weakly emissive in fluid solutions at 298 K but showed intense luminescence in low-temperature glass. In view of the structured emission profiles and the long lifetimes, the emission of all of the complexes has been assigned to a triplet intraligand ((3)IL) (pi --> pi*) (pba) excited state, which was probably mixed with some triplet metal-to-ligand charge-transfer ((3)MLCT) [dpi(Ir or Rh) --> pi*(pba)] character. To investigate the reactivity of the aldehyde groups, complex 2 was reacted with n-butylamine, resulting in the formation of the complex [Ir(ppy-CH(2)NHC(4)H(9))(2)(bpy-TEG-biotin)](PF(6)) (2a) [Hppy-CH(2)NHC(4)H(9) = 2-[4-[N-(n-butyl)aminomethyl]phenyl]pyridine]. All of the aldehyde complexes have been used to biotinylate bovine serum albumin (BSA) to form bioconjugates 1-BSA-5-BSA. The bioconjugates have been isolated, purified, and characterized and their photophysical properties studied. Upon photoexcitation, all of the bioconjugates were luminescent and the emission has been attributed to a (3)MLCT [dpi(Ir) --> pi*(N(wedge)N)] state for the iridium(III) conjugates and a mixed (3)IL (pi --> pi*) (N(wedge)N and N(wedge)C)/(3)MLCT [dpi(Rh) --> pi*(N(wedge)N)] state for the rhodium(III) conjugates. The avidin-binding properties of complexes 1, 2, 2a, and 3 and bioconjugates 1-BSA-3-BSA have been investigated using the 4'-hydroxyazobenzene-2-carboxylic acid assay. Emission titrations showed that complex 2a displayed a significant change of the emission profile upon binding to avidin. Additionally, the cytotoxicity of all of the iridium(III) and rhodium(III) complexes toward the human cervix epithelioid carcinoma cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay. Furthermore, the cellular uptake properties of the complexes and bioconjugate 2-BSA have been investigated by laser-scanning confocal microscopy.

Synthesis, photophysical and electrochemical properties, and protein-binding studies of luminescent cyclometalated iridium(III) bipyridine estradiol conjugates.

A new series of luminescent cyclometalated iridium(III) bipyridine estradiol conjugates [Ir(N-C)2(N-N)](PF6) (N-N = 5-(4-(17alpha-ethynylestradiolyl)phenyl)-2,2'-bipyridine, bpy-est, HN-C = 2-phenylpyridine, Hppy (1 a), 1-phenylpyrazole, Hppz (2 a), 7,8-benzoquinoline, Hbzq (3 a), 2-phenylquinoline, Hpq (4 a), 2-((1,1'-biphenyl)-4-yl)benzothiazole, Hbsb (5 a); N-N = 4-(N-(6-(4-(17alpha-ethynylestradiolyl)benzoylamino)hexyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, bpy-C6-est, HN-C = Hppy (1 b), Hppz (2 b), Hbzq (3 b), Hpq (4 b), Hbsb (5 b)) was synthesized, characterized, and their photophysical and electrochemical properties studied. Upon photoexcitation, all the complexes displayed intense and long-lived emission in fluid solutions at 298 K and in low-temperature glass. The emission of complexes 1 a-3 a and 1 b-3 b was assigned to a triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir)-->pi*(bpy-est and N-C-)) state mixed with some triplet intraligand ((3)IL) (pi-->pi*) (N-C- and N-N) character. However, the emissive states of the pq- and bsb- complexes 4 a, 4 b, 5 a, and 5 b showed substantial (3)IL (pi-->pi*) (pq-/bsb-) character. The lipophilicity of all the complexes was determined by reversed-phase HPLC. Upon binding to estrogen receptor alpha, all of these iridium(III) estradiol conjugates exhibited emission enhancement and lifetime extension, rendering them a novel series of luminescent probes for this receptor.