A Radioimmunoassay for Measurement of 3,3′, 5′-Triiodothyronine (Reverse T3)

A highly specific antiserum to 3,3',5'-triiodothyronine (reverse T(3), rT(3)) was prepared by immunization of rabbits with D,L-rT(3)-human serum albumin conjugate. Of the various thyroid hormone derivatives tested, only 3,3'-diiodothyronine (3,3'-T(2)) cross-reacted significantly (10%) with rT(3)-binding sites on the antiserum, while thyroxine (T(4)) and triiodothyronine (T(3)) cross-reacted by less than 0.1%. The antiserum was used in a simple, sensitive, precise, and reproducible radioimmunoassay (RIA) for measurement of rT(3) in ethanolic extracts of serum. The dose-response curves of inhibition of the binding of [(125)I]rT(3) to antibody obtained by serial dilutions of serum extracts were essentially parallel to the standard assay curve. Recovery of nonradioactive rT(3) added to serum before extraction averaged 93%.Serum rT(3) concentrations were found to be (mean+/-SD) 41+/-10 ng/100 ml in 27 normal subjects, 103+/-49 ng/100 ml in 22 hyperthyroid patients, 19+/-9 ng/100 ml in 12 hypothyroid patients, and 54+/-7 ng/100 ml in five subjects with elevated serum thyroxine-binding globulin: the values in each of the latter three groups of individuals were significantly different from normal. Reverse T(3) was detected regularly in normal or supranormal concentrations in serum of 12 hypothyroid patients rendered euthyroid or mildly hyperthyroid by treatment with synthetic T(4). It is suggested that serum rT(3) values noted here should be taken to reflect the relative changes in serum rT(3) rather than its absolute values in health and thyroid disease. True serum rT(3) may be somewhat different because: (a) D.L-rT(3) employed in the standard curve and L-rT(3) present in human serum may react differently with anti-D,L-rT(2). (b) Even though 3,3'-T(2), which cross-reacted 10% in rT(3) RIA, has been considered unlikely to be present in human serum, it may circulate in low levels. (c) Cross-reaction of T(4) in rT(3) RIA of 0.06% although small, could contribute to RIA estimates of rT(2); the effect of T(4) would be particularly important in case of serum of hyperthyroid patients. Thus, serum rT(3) concentration in hyperthyroid patients averaged 89+/-48 mug/100 ml after correction for cross-reaction effects of T(4): this value was about 14% lower than that before correction (see above).Serum rT(3) concentration in cord sera of seven newborns averaged 136+/-19 ng/100 ml; it was clearly elevated and within the range of values seen in hyperthyroid patients. This was the case when the mean T(4) concentration in the newborn cord sera was moderately higher than normal and about one-half that in hyperthyroid patients, whereas serum T(3) was markedly below the normal adult level. A Pronase hydrolysate of thyroglobulin prepared from pooled normal thyroid glands contained 0.042, 3.0, and 0.16 mug/mg protein of rT(3), T(4), and T(3), respectively. The various data suggest that: (a) rT(3) is a normal component of human serum and thyroglobulin: (b) peripheral metabolism of T(4) is an important source of the rT(3) present in serum: (c) peripheral conversion of T(4) to T(3) and rT(3) may not necessarily be a random process.     

Reactive molecular dynamics simulation of the high-temperature pyrolysis of 2,2′,2′′,4,4′,4′′,6,6′,6′′-nonanitro-1,1′:3′,1′′-terphenyl (NONA)

2,2′,2′′,4,4′,4′′,6,6′,6′′-Nonanitro-1,1′:3′,1′′-terphenyl (NONA) is currently recognized as an excellent heat-resistant explosive. To improve the atomistic understanding of the thermal decomposition paths of NONA, we performed a series of reactive force field (ReaxFF) molecular dynamics simulations under extreme conditions of temperature and pressure. The results show that two distinct initial decomposition mechanisms are the homolytic cleavage of the C–NO₂ bond and nitro–nitrite (NO₂ → ONO) isomerization followed by NO fission. Bimolecular and fused ring compounds are found in the subsequent decomposition of NONA. The product identification analysis under finite time steps showed that the gaseous products are CO₂, N₂, and H₂O. The amount of CO₂ is energetically more favorable for the system at high temperature or low density. The carbon-containing clusters are a favorable growth pathway at low temperatures, and this process was further demonstrated by the analysis of diffusion coefficients. The increase of the crystal density accelerates the decomposition of NONA judged by the analysis of reaction kinetic parameters and activation barriers. In the endothermic and exothermic stages, a 20% increase in NONA density increases the activation energies by 3.24 and 0.48 kcal mol⁻¹, respectively. The values of activation energies (49.34–49.82 kcal mol⁻¹) agree with the experimental data in the initial decomposition stage.

The bimolecular and fused ring compounds are found in the high-temperature pyrolysis of NONA using ReaxFF molecular dynamics simulations.     

Synthesis,cytotoxicity evaluation and molecular docking studies on 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone derivatives

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC, 1) was isolated from seeds of Syzygium nervosum A.Cunn. ex DC. exhibiting intriguing biological activities. Herein, thirty three DMC derivatives including 4′-O-monosubstituted-DMC (2), 7-O-acylated-4-hydroxycoumarin derivatives (3), stilbene–coumarin derivatives (4), 2′,4′-disubstituted-DMC (5), and flavanone derivatives (6), were synthesised through acylation, alkylations, and sulfonylation. These semi-synthetic DMC derivatives were evaluated for in vitro cytotoxicity against six carcinoma cell lines. It was found that most derivatives exhibited higher cytotoxicity than DMC. In particular, 4′-O-caproylated-DMC (2b) and 4′-O-methylated-DMC (2g) displayed the strongest cytotoxicity against SH-SY5Y with IC₅₀ values of 5.20 and 7.52 μM, respectively. Additionally, 4′-O-benzylated-DMC (2h) demonstrated the strongest cytotoxicity against A-549 and FaDu with IC₅₀ values of 9.99 and 13.98 μM, respectively. Our structure–activity relationship (SAR) highlights the importance of 2′-OH and the derivatisation pattern of 4′-OH. Furthermore, molecular docking simulation studies shed further light on how these bioactive compounds interact with cyclin-dependent kinase 2 (CDK2).

Semi-synthetic DMC derivatives were synthesised and displayed biological potency against various cancer cell lines.      

The Effect of 3′,5′-Adenosine Monophosphate on Granulocyte Adhesion

Human granulocyte adhesion to glass capillary tubes was tested in the presence of agents that increase intracellular levels of cyclic 3′,5′-adenosine monophosphate (cAMP). Adhesion was significantly reduced by 10^-3-10^-4 M dibutyryl cAMP, 10^-4-10^-6 M prostaglandin E₁ (PGE₁), 10^-4-10^-6 M histamine, or 10^-3 M theophylline. Adhesion was not suppressed by 10^-4 M theophylline unless it was combined with PGE₁ or histamine. Eosinophil and basophil adhesion was especially sensitive to suppression by the above agents. These findings suggest that intracellular cAMP may play a role in regulation of adhesiveness of human basophils, eosinophils, and neutrophils.     

Elucidating the intramolecular contrast in the STM images of 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules recorded at room-temperature and at the liquid-solid interface

Star-shaped 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules self-assemble at the solid–liquid interface into a compact hexagonal nanoarchitecture on graphite. High resolution scanning tunneling microscopy (STM) images of the molecules reveal intramolecular features. Comparison of the experimental data with calculated molecular charge density contours shows that the molecular features in the STM images correspond to molecular LUMO+2.

Intramolecular contrast in the STM images of 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules recorded at room-temperature and at the liquid–solid interface.     

Effects of glucagon on adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in human plasma and urine

Glucagon, infused intravenously into fasting, well-hydrated, normal men in doses of 25-200 ng/kg per min, induced up to 30-fold increases in both plasma and urinary cyclic AMP. Cyclic GMP levels were unaffected by glucagon. Simultaneous cyclic AMP and inulin clearance studies demonstrated that the glucagon-induced increase in urinary cyclic AMP was entirely due to glomerular filtration of the elevated plasma levels of the nucleotide.The cyclic AMP response to glucagon was not mediated by parathyroid hormone or epinephrine, and trypsintreated glucagon was completely inactive.The perfused rat liver released cyclic AMP into the perfusate in response to glucagon, indicating that the liver is a possible source of the cyclic AMP entering the extracellular fluids in response to glucagon in vivo.     

Mimicking 2,2′:6′,2′′:6′′,2′′′-quaterpyridine complexes for the light-driven hydrogen evolution reaction: synthesis,structural, thermal and physicochemical characterizations

The synthetic difficulties associated with quaterpyridine (qtpy) complexes have limited their use in the formation of various metallosupramolecular architectures in spite of their diverse structural and physicochemical properties. Providing a new facile synthetic route to the synthesis of functionalised qtpy mimics, we herein report the synthesis of three novel –NH₂ functionalized qtpy-like complexes 12–14 with the general formula M(C₁₆H₁₄N₁₂)(NO₃)₂ (M = Co(ii), Ni(ii) and Cu(ii)) in high yield and purity. Characterization of these complexes has been done by single crystal X-ray diffraction (SCXRD), thermogravimetric analysis, UV-Vis, infrared, mass spectrometry and cyclic voltammetry. As indicated by SCXRD, in all the synthesized complexes, the metal ions show a strongly distorted octahedral coordination geometry and typical hydrogen bonding networks involving DAT groups. In addition, complexes 12–14 have been analyzed as potential photocatalysts for hydrogen evolution reaction (HER) displaying good turnover numbers (TONs). Hydrogen produced from these photocatalysts can serve as the possible alternative for fossil fuels. To the best of our knowledge, this is the only study showcasing –NH₂ functionalized qtpy-like complexes of Co(ii), Ni(ii) and Cu(ii) and employing them as photocatalysts for HER. Thus, a single proposed strategy solves two purposes-one related to synthesis while second is related to our environment.

Facile synthesis of three novel –NH₂ functionalized qtpy-like complexes, their characterizations and study of their photocatalytic properties for hydrogen evolution reaction.     

Cyclic 3′,5′-adenosine monophosphate in human blood platelets: II. Effect of N6-2′-0-dibutyryl cyclic 3′,5′-adenosine monophosphate on platelet function

The relation of cyclic 3',5'-adenosine monophosphate to platelet function has been studied by investigating the influence of this compound and of its N(6)-2'-0-dibutyryl derivative on platelet aggregation and other aspects of platelet behavior after demonstration of adenyl cyclase activity in disrupted platelets.Dibutyryl cyclic AMP inhibited platelet aggregation induced by ADP, epinephrine, collagen, and thrombin. Cyclic AMP was also inhibitory but was less effective. The platelet "release reaction" was also inhibited; specifically, there was inhibition of the induction of platelet factor 3 activity and of the release of labeled 5-hydroxytryptamine. Platelet swelling produced by ADP was not inhibited.The action of dibutyryl cyclic AMP did not result from contamination with 5'-AMP, nor was it attributable to production of 5'-AMP by plasma enzymes. Dibutyryl cyclic AMP was degraded to 2'-O-monobutyryl cyclic AMP and to cyclic AMP in plasma, but plasma exhibited no cyclic nucleotide phosphodiesterase activity, and the production of 5'-AMP did not occur. The in vitro effects of dibutyryl cyclic AMP were associated with uptake of the compound by platelets.Adenyl cyclase activity of platelet homogenates was demonstrated with production of 9.27 x 10(-11) (+/-2.62 x 10(-11)) mole cyclic AMP per min per 10(10) platelets. The activity was increased by NaF and by prostaglandin PGE(1) and was decreased by epinephrine. The effect of epinephrine was blocked by phentolamine but not by propanolol. Adenyl cyclase activity was also inhibited by collagen, 5-hydroxytryptamine, and thrombin. ADP, dibutyryl cyclic AMP, and cyclic AMP did not alter adenyl cyclase activity.These observations are consistent with the hypothesis that platelet aggregation is favored by a decrease in platelet cyclic AMP and inhibited by an increase in cyclic AMP.     

Renal effects of adenosine 3′,5′-cyclic monophosphate and dibutyryl adenosine 3′,5′-cyclic monophosphate: Evidence for a role for adenosine 3′,5′-cyclic monophosphate in the regulation of proximal tubular sodium reabsorption

Stable water diuresis was produced in anesthetized, hydrocortisone-treated hypophysectomized dogs by infusion of 2.5% dextrose. Infusion of adenosine 3',5'-cyclic monophosphate (cyclic AMP) in the left renal artery decreased ipsilaterally glomerular filtration rate (GFR), cortical and non-cortical renal plasma flow, and tended to increase urine flow (V) and free-water clearance (C(H2O)) despite a decrease in mean arterial pressure. Infusion of dibutyryl adenosine 3',5'-cyclic monophosphate (dibutyryl cyclic AMP) in the left renal artery increased V and C(H2O) significantly (P<0.01) bilaterally with essentially no change in GFR, in total renal plasma flow or its cortical and non-cortical components. For each kidney the magnitude of the change in V was similar to the magnitude of the change in C(H2O) and the change in sodium excretion was trivial. Cyclic AMP probably produced its effects on renal hemodynamics and mean arterial pressure wholly or in part through the action of metabolites such as 5'-AMP and adenosine on the renal and systemic vasculature. The absence of an effect of dibutyryl cyclic AMP on renal hemodynamics and its bilateral effect may be explained by the resistance of this nucleotide derivative to metabolism.Dibutyryl cyclic AMP appears to decrease by direct cellular effect(s) proximal tubular sodium reabsorption but does not prevent virtually complete reabsorption of the increased load of sodium in the distal nephron. This effect on the kidney is qualitatively and quantitatively similar to the effect of renal arterial infusion of isoproterenol.The results suggest that synthesis of cyclic AMP in proximal renal tubule cells in response to stimulation of beta adrenergic or other receptors can mediate a decrease in the proximal tubular reabsorption of sodium.     

Pharmacokinetics and Distribution over the Blood-Brain Barrier of Zalcitabine (2′,3′-Dideoxycytidine) and BEA005 (2′,3′-Dideoxy-3′-Hydroxymethylcytidine) in Rats, Studied by Microdialysis

Microdialysis was applied to sample the unbound drug concentration in the extracellular fluid in brain and muscle of rats given zalcitabine (2′,3′-dideoxycytidine; n = 4) or BEA005 (2′,3′-dideoxy-3′-hydroxymethylcytidine; n = 4) (50 mg/kg of body weight given subcutaneously). Zalcitabine and BEA005 were analyzed by high-pressure liquid chromatography with UV detection. The maximum concentration of zalcitabine in the dialysate (C_max) was 31.4 ± 5.1 μM (mean ± standard error of the mean) for the brain and 238.3 ± 48.1 μM for muscle. The time to C_max was found to be from 30 to 45 min for the brain and from 15 to 30 min for muscle. Zalcitabine was eliminated from the brain and muscle with half-lives 1.28 ± 0.64 and 0.85 ± 0.13 h, respectively. The ratio of the area under the concentration-time curve (AUC) (from 0 to 180 min) for the brain and the AUC for muscle (AUC ratio) was 0.191 ± 0.037. The concentrations of BEA005 attained in the brain and muscle were lower than those of zalcitabine, with C_maxs of 5.7 ± 1.4 μM in the brain and 61.3 ± 12.0 μM in the muscle. The peak concentration in the brain was attained 50 to 70 min after injection, and that in muscle was achieved 30 to 50 min after injection. The half-lives of BEA005 in the brain and muscle were 5.51 ± 1.45 and 0.64 ± 0.06 h, respectively. The AUC ratio (from 0 to 180 min) between brain and muscle was 0.162 ± 0.026. The log octanol/water partition coefficients were found to be −1.19 ± 0.04 and −1.47 ± 0.01 for zalcitabine and BEA005, respectively. The degrees of plasma protein binding of zalcitabine (11% ± 4%) and BEA005 (18% ± 2%) were measured by microdialysis in vitro. The differences between zalcitabine and BEA005 with respect to the AUC ratio (P = 0.481), half-life in muscle (P = 0.279), and level of protein binding (P = 0.174) were not statistically significant. The differences were statistically significant in the case of the half-life in the brain (P = 0.032), clearance (P = 0.046), volume of distribution (P = 0.027) in muscle, and octanol/water partition coefficient (P = 0.019).     

Abnormal regulation of adenosine 3′,5′-monophosphate and corticosterone formation in an adrenocortical carcinoma

A spontaneously occurring rat adrenocortical carcinoma which produces corticosterone was maintained by transplantation. The carcinoma appeared to utilize corticosterone biosynthetic steps similar to those of the normal adrenal, but the tumor produced only about 1-10% as much corticosterone per unit tissue weight as nontumorous adrenal glands. The tumor demonstrated little or no increase in corticosterone production in response to adrenocorticotropic hormone (ACTH) either in vivo or in vitro.In normal adrenals, ACTH increases the activity of adenyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine-3',5'-monophosphate (cyclic AMP), the latter then serving as an intracellular regulator of steroidogenesis. ACTH failed to increase cyclic AMP levels in the tumor in vivo or in slices in vitro, conditions under which there were 50- and 20-fold increases in nontumorous adrenals. However, in homogenates fortified with exogenous ATP, adenyl cyclase activity was comparable in the tumor and adrenals, and cyclic AMP formation was increased 3-fold by ACTH in each. As measured in homogenates, the tumor did not possess a greater ability to destroy cyclic AMP than did normal adrenals. Although ATP levels in the carcinoma were found to be considerably lower than those in normal adrenals, it was not clear that this finding can explain the inability of ACTH to increase cyclic AMP levels in intact tumor cells.While the failure to normally influence cyclic AMP levels in the carcinoma cells could be an important factor in the lack of a steroid response to ACTH, several lines of evidence suggest that the tumor possesses one or more additional abnormalities in the regulation of steroidogenesis. First, in the absence of ACTH stimulation, the tissue concentrations of cyclic AMP were comparable in the tumor and in nontumorous adrenals, but these cyclic AMP levels were associated with a lower level of steroidogenesis in the tumor. Second, tumor slices failed to increase corticosterone production when incubated with cyclic AMP, in contrast to 5-fold increases observed with nontumorous adrenals.     

Effect of adenosine 3′,5′-monophosphate on production of glucose and ammonia by renal cortex

In studies employing rat renal cortical slices, the addition of adenosine 3',5'-monophosphate (cyclic AMP) to the incubation medium caused an increase in production of glucose from glutamine, glutamate, alpha-ketoglutarate, fumarate, malate, and oxalacetate, but not from glycerol and fructose. These observations suggest that cyclic AMP accelerates a rate-limiting gluconeogenic reaction between oxalacetate and the triose phosphates. The addition to the medium of parathyroid hormone, which is known to increase renal cortical cyclic AMP, also stimulated glucose production from glutamine.When renal cortical slices were incubated in the presence of glutamine, the addition of cyclic AMP caused a fall in tissue glutamate concentration and a rise in ammonia production, as well as an increase in gluconeogenesis. These changes are similar to those observed in renal cortex of rats with induced metabolic acidosis. The present observations are consistent with a previously advanced hypothesis that cortical gluconeogenesis, ammonia production, and glutamate concentration may be interdependent.     

A promising TNT alternative 3,3′-bi(1,2,4-oxadiazole)-5,5′-diylbis(methylene)dinitrate (BOM): thermal behaviors and eutectic characteristics

3,3′-Bi(1,2,4-oxadiazole)-5,5′-diylbis(methylene)dinitrate (BOM) is a liquid phase carrier for melt cast explosives that is expected to replace TNT. The combination of a conjugated 1,2,4-oxadiazole backbone and nitrate ester groups endows BOM with both good energetic performance and impressive insensitivity. In this paper, the thermal behaviors of BOM were investigated using a TG–DSC synchronous thermal analyzer, proving that BOM is basically non-volatile under heating and melting processes. The apparent activation energy of BOM calculated by the Kissinger method was 158.2 kJ mol⁻¹ at atmospheric pressure, which is higher than that of DNTF at atmospheric pressure and TNT at 2 MPa, indicating good thermal stability at low temperatures. The thermal decomposition mechanism of BOM was studied through both DSC-MS and in situ FTIR technologies. The low eutectic characteristics of BOM and DNTF were also investigated carefully and the best ratio of BOM/DNTF was 40/60 with a melting point at 75.5 °C. Finally, the detonation performances of TNT/HMX, BOM/HMX and BOM/DNTF(40/60)/HMX explosive formulations were calculated, showing that the detonation performances of the latter two formulations were significantly higher than that of TNT/HMX.

3,3′-Bi(1,2,4-oxadiazole)-5,5′-diylbis(methylene)dinitrate (BOM) is a liquid phase carrier for melt cast explosives that is expected to replace TNT.     

Effect of dibutyryl cyclic adenosine 3′,5′-monophosphate, theophylline, and other nucleotides upon calcium and phosphate metabolism

The effect of dibutyryl cyclic adenosine 3',5'-monophosphate upon calcium and phosphate metabolism in thyroparathyroidectomized rats was undertaken in an effort to clarify the possible role of adenosine 3',5'-monophosphate (3',5' AMP) in parathyroid hormone action. The infusion of dibutyryl cyclic 3',5' AMP at a rate of 3 mg/hr into thyroparathyroidectomized rats leads to changes in calcium, phosphate, and hydroxyproline excretion, and calcium and phosphate concentrations in plasma that are qualitatively similar to those induced by parathyroid hormone given at a rate of 5 mug/hr. The effect of dibutyryl cyclic 3',5' AMP upon calcium and hydroxyproline mobilization from bone is blocked by thyrocalcitonin administration in the same way that thyrocalcitonin blocks PTH effects. Other closely related nucleotides do not act in the same way.These data indicate that dibutyryl cyclic 3',5' AMP produces effects similar to parathyroid hormone in thyroparathyroidectomized rats, and support the notion that 3',5' AMP is an intermediate in the mechanism of PTH action. However, the changes in magnesium and potassium excretion are different after dibutyryl cyclic 3',5' AMP infusion from those seen after PTH infusion. Also, theophylline was found to potentiate the action of smaller doses of dibutyryl 3',5' AMP, but not that of PTH.     

Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines

Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with (R)-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the (R)-enantiomers could be produced with 88–89% conversion and >99% ee, while the (S)-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee.

Immobilised whole-cell (R)-transaminases (TAs) enabled synthesis of either (R)- or (S)-enantiomers of drug-like amines from prochiral ketones or from racemic amines, respectively, in >95% ee.     

Improvement of In Vitro and In Vivo Antileishmanial Activities of 2′,6′-Dihydroxy-4′-Methoxychalcone by Entrapment in Poly(d,l-Lactide) Nanoparticles

The inhibition of intracellular Leishmania amazonensis growth by 2', 6'-dihydroxy-4'-methoxychalcone (DMC) isolated from Piper aduncum was further enhanced after encapsulation of DMC in polymeric nanoparticles. Encapsulated DMC also showed increased antileishmanial activity in infected BALB/c mice, as evidenced by significantly smaller lesions and fewer parasites in the lesions.     

Organic binary charge-transfer compounds of 2,2′ : 6′,2′′ : 6′′,6-trioxotriphenylamine and a pyrene-annulated azaacene as donors

Three binary charge-transfer (CT) compounds resulting from the donor 2,2′ : 6′,2′′ : 6′′,6-trioxotriphenylamine (TOTA) and the acceptors F₄TCNQ and F₄BQ and of a pyrene-annulated azaacene (PAA) with the acceptor F₄TCNQ are reported. The identity of these CT compounds are confirmed by single-crystal X-ray diffraction as well as by IR, UV-vis-NIR and EPR spectroscopy. X-ray diffraction analysis reveals a 1 : 1 stoichiometry for TOTA·F₄TCNQ, a 2 : 1 donor : acceptor ratio in (TOTA)₂·F₄BQ, and a rare 4 : 1 stoichiometry in (PAA)₄·F₄TCNQ, respectively. Metrical parameters of the donor (D) and acceptor (A) constituents as well as IR spectra indicate full CT in TOTA·F₄TCNQ, partial CT in (TOTA)₂·F₄BQ and only a very modest one in (PAA)₄·F₄TCNQ. Intricate packing motifs are present in the crystal lattice with encaged, π-stacked (F₄TCNQ⁻)₂ dimers in TOTA·F₄TCNQ or mixed D/A stacks in the other two compounds. Their solid-state UV-vis-NIR spectra feature CT transitions. The CT compounds with F₄TCNQ are electrical insulators, while (TOTA)₂·F₄BQ is weakly conducting.

Three binary charge-transfer (CT) compounds resulting from the donor 2,2′ : 6′,2′′ : 6′′,6-trioxotriphenylamine (TOTA) and the acceptors F₄TCNQ and F₄BQ and of a pyrene-annulated azaacene (PAA) with the acceptor F₄TCNQ are reported.     

Cyclic 3′,5′-adenosine monophosphate in the human leukocyte: synthesis, degradation, and effects on neutrophil candidacidal activity

Prostaglandins E(1) and E(2) (PGE(1) and PGE(2)) stimulate adenyl cyclase activity in broken cell preparations of normal human leukocytes, whereas prostaglandin F(1a) produces no effect. PGE(1) and PGE(2) also cause increased accumulation of cyclic 3',5'-adenosine monophosphate-(3)H ((3)H-labeled AMP) in intact leukocytes which have been preincubated with adenine-(3)H in vitro. Theophylline inhibits leukocyte phosphodiesterase activity and potentiates the stimulatory effect of the prostaglandins on intracellular accumulation of cyclic 3',5'-AMP-(3)H.The ability of human granulocytes in vitro to kill Candida albicans was consistently inhibited by PGE(1) and theophylline. This effect was reproduced by dibutyryl cyclic 3',5'-AMP, a lipid-soluble analogue of the endogenous nucleotide. The inhibition of candidacidal activity could not be accounted for by drug effects on phagocytosis, oxygen consumption, or hexose monophosphate shunt activity. These results are consistent with the hypothesis that increased intracellular concentrations of cyclic 3',5'-AMP impair the granulocyte's ability to kill C. albicans, but the precise mechanism of inhibition has not yet been defined.     

Effects of glucagon, dibutyryl cyclic 3′,5′-adenosine monophosphate, and theophylline on calcitonin secretion in vitro

The secretion of calcitonin by slices of porcine thyroid glands has been investigated. Calcitonin in the incubation medium was determined by radioimmunoassay. Secretion of calcitonin was diminished when calcium or magnesium was omitted and was increased stepwise as the concentration of calcium or magnesium in the incubation medium was increased. Calcitonin secretion was augmented substantially when either the quantity of thyroid tissue or volume of incubation medium was increased. Secretion of calcitonin was stimulated by glucagon, theophylline, and dibutyryl cyclic 3',5'-adenosine monophosphate. It is concluded that calcitonin secretion is regulated by the concentration of calcium and magnesium, that secretion may be inhibited by calcitonin or a precursor and that secretion can be stimulated by increasing the concentration of cyclic 3',5'-adenosine monophosphate in the parafollicular cells of the thyroid gland.     

Convenient and sensitive colorimetric detection of melamine in dairy products based on Cu(ii)-H2O2-3,3′,5,5′-tetramethylbenzidine system

The illegal adulteration of melamine in dairy products for false protein content increase is a strong hazard to human health. Herein, a simple and sensitive colorimetric method was developed for the quantification of melamine in dairy products based on a Cu²⁺-hydrogen peroxide (H₂O₂)-3,3′,5,5′-tetramethylbenzidine (TMB) system. In this strategy, Cu²⁺ exhibits peroxidase-like activity and can catalyze the oxidation of TMB to oxidized TMB (oxTMB) in the presence of H₂O₂ with a blue colour change of the solution. However, the presence of melamine quickly interacts with H₂O₂ leading to the consumption of H₂O₂ and thus strongly hinders the oxidation of TMB. Under the optimal conditions, the absorbance change of oxTMB has a linear response to the concentration of melamine from 1 to 100 μM with a detection limit of 0.5 μM for melamine. The proposed method has many merits including more simplicity, good selectivity, and more cost-effectiveness without using any nanomaterials. The method was further successfully applied to detect melamine in dairy products including milk and infant formula powder.

Convenient and sensitive colorimetric detection of melamine in dairy products based on a Cu(ii)-H₂O₂-3,3′,5,5′-tetramethylbenzidine system was reported.