Syntheses and β‐adrenergic binding affinities of (R)‐ and (S)‐fluoronaphthyloxypropanolamines

The β‐adrenergic receptors mediate several physiological processes including heart rate (β₁), bronchodilation (β₂), and lipolysis (β₃). Therefore, selectivity is important for a possible therapeutic agent acting via these receptors. Aryloxypropanolamines are β‐receptor agonists or antagonists, depending on the aryl group and its substituents. We therefore hypothesized that fluorine substitution on the aromatic ring in this class could lead to significant biological effects because of the unique chemical characteristics of fluorine. Because the target compound has a chiral center, we set out to synthesize the two enantiomers so that effects of stereochemistry on biological activity could be evaluated. Syntheses of the enantiomers were performed starting with commercially available fluoronaphthalene and subsequent use of the chiral synthon (2R)‐ or (2S)‐glycidyl 3‐nitrobenzenesulfonate, depending on the desired enantiomer. High‐pressure liquid chromatography (HPLC) methods were used to characterize %ee. Each enantiomer was synthesized. They exhibited nanomolar binding activities on β‐adrenergic receptors. The (S)‐enantiomer was found to be up to 310 times more potent than the (R). It was also found to be about five‐fold more selective for β₂‐ than for β₁‐receptors. The current report demonstrates the importance of stereochemistry for the fluoroaromatic β‐receptor ligands. Chirality 11:144–148, 1999. © 1999 Wiley‐Liss, Inc.     

Familial whole-arm translocations (1;19), (9;13), and (12;21): a review of 101 constitutional exchanges

We report here on 3 familial whole-arm translocations (WATs), namely the 8th instance of t(1;19)(p10;q10) and 2 novel exchanges: t(9;13)(p10;q10) and t(12;21)(p10;q10). The exchanges (1;19) and (12;21) were ascertained through a balanced carrier, whereas the t(9;13) was first diagnosed in a boy with a trisomy 9p syndrome and der(9p13p). Results of FISH analyses with the appropriate α-satellite probes were as follows. Family 1, t(1;19): the D1Z5 probe gave a strong signal on both the normal chromosome 1 and the der(1q19p) as well as a weak signal on the der(1p19q). Family 2, t(9;13): the centromere-9 alphoid and D13Z1/D21Z1 probes under standard stringency gave no signal on the der(9p13p) in both the proband and a carrier brother, whereas the der(9q13q) was labelled only with the centromere-9 alphoid repeat in the latter; yet, this probe under low stringency revealed a residual amount of alphoid DNA on the der(9p13p) in the carrier. Family 3, t(12;21): the D12Z3 probe gave a signal on the normal chromosome 12 and the der(12p21q), whereas the D13Z1/D21Z1 repeat labelled the der(12q21p), the normal chromosome 21, and both chromosomes 13. Out of 101 WATs compiled here, 73 are distinct exchanges, including 32 instances between chromosomes with common alphoid repeats. Moreover, 7/9 of recurrent WATs involved chromosomes from the same alphoid family. Thus constitutional WATs appear to recur more frequently than other reciprocal exchanges, often involve chromosomes with common alphoid repeats, and can mostly be accounted for the great homology in alphoid DNA that favours mispairing and illegitimate nonhomologous recombination.     

Synthesis of divalent beta-(1-->6)-branched (1-->3)-glucohexaose and trivalent beta-(1-->6)-branched (1-->3)-glucotriose

Hexaose, beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-alpha-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp, based dimers were synthesized by twofold glycosidation of the hexaosyl trichloroacetimidate with hexylene 1,6-diol, diethylene glycol and triethylene glycol, respectively. Meanwhile, a triose, beta-1D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp, based trimer was obtained by glycosidation of the triosyl trichloroacetimidate with a glycerol-derived triol scaffold.     

Synthesis by Ring‐Closing Alkyne Metathesis with Selective Hydrogenation,and Olfactory Comparison of (7E)‐ and (7Z)‐Cyclohexadec‐7‐enone (Aurelione®)

Both C?C‐bond isomers of cyclohexadec‐7‐enone ( 6 , Aurelione^®) were selectively synthesized via cyclohexadec‐7‐ynol ( 16 ) by ring‐closing alkyne metathesis of icosa‐2,18‐diyn‐9‐ol ( 15 ), employing an in situ‐formed catalyst from Mo(CO)₆ and 4‐(trifluoromethyl)phenol. Pyridinium chlorochromate (PCC) oxidation and subsequent Lindlar hydrogenation afforded the (7Z)‐configured isomer (7Z)‐ 6 , while hydrosilylation of the intermediate cyclohexadec‐7‐ynone ( 17 ), followed by desilylation, provided the (7E)‐configured cyclohexadec‐7‐enone ((7E)‐ 6 ). The substrate for the alkyne metathesis was prepared from cycloheptanone ( 7 ) by cycloaddition of chloromethylcarbene to its trimethylsilyl enol ether 8 , and subsequent ring enlargement of the adduct 9 under rearrangement to 2‐methylcyclooct‐2‐enone ( 10 ), which was subjected to Weitz? Scheffer epoxidation and Eschenmoser? Ohloff fragmentation to non‐7‐ynal ( 12 ). Its reaction with the Grignard reagent of 11‐bromoundec‐2‐yne ( 14 ), prepared from the corresponding alcohol 13 by Appel? Lee bromination, furnished the icosa‐2,18‐diyn‐9‐ol ( 15 ). While both isomers of cyclohexadec‐7‐enone ( 6 ) possess warm and powdery musk odors with tobacco‐type ambery accents, (7Z)‐ 6 is more animalic and waxy, whereas (7E)‐ 6 was found to be more floral, sweet, and hay‐like in tonality. Interestingly, however, with odor detection thresholds of 2.0 ng/l air and 2.3 ng/l air, respectively, both (7Z)‐ 6 and (7E)‐ 6 were found to be almost identical in their odor strength, with the (7Z)‐ 6 being only very slightly more powerful.     

Botanical-geographical and forestry aspects of introgressive hybridization of the Gmelin’s larch (<Emphasis Type="Italic">Larix gmelinii</Emphasis> (Rupr.) Rupr.) and Cajander larch (<Emphasis Type="Italic">L. cajanderi</Emphasis> Mayr)

The paper studies the introgressive hybridization between the Gmelin’s larch and Cajander larch. The obtained data confirm the indisputable specific independence of the Cajander larch, which occupies about 48% of the total area of the larch forests in Russia. Its specific independence has been doubted by some experts. Once again more reliable and vast material shows the presence of wide transitional belt of hybrid populations at the juncture of the hybridizing species. Some forestry characteristics of the Gmelin’s larch and Cajanderi larch are studied that play important role in their natural restoration.     

A jumping translocation (5p;15q), (8q;15q), and (12q;15q) (author's transl)]

Three balanced karyotypes (5p;15q), (8q;15q), and (12q;15q) were found simultaneously in a child with the Willi-Prader syndrome. The hypothesis is presented of a "jumping# translocation by affinity of telomeric and interstitial palindromes. The relationship between the Willi-Prader syndrome and a juxtacentric anomaly of the long arm of chromosome 15 is discussed.     

White‐ and blue‐light‐emitting dysprosium(III) and terbium(III)‐doped gadolinium titanate phosphors

Here we report the synthesis and structural, morphological, and photoluminescence analysis of white‐ and blue‐light‐emitting Dy³⁺‐ and Tm³⁺‐doped Gd₂Ti₂O₇ nanophosphors. Single‐phase cubic Gd₂Ti₂O₇ nanopowders consist of compact, dense aggregates of nanoparticles with an average size of ~25 nm for Dy³⁺‐doped and ~50 nm for Tm³⁺‐doped samples. The photoluminescence results indicated that ultraviolet (UV) light excitation of the Dy³⁺‐doped sample resulted in direct generation of white light, while a dominant yellow emission was obtained under blue‐light excitation. Intense blue light was obtained for Tm³⁺‐doped Gd₂Ti₂O₇ under UV excitation suggesting that this material could be used as a blue phosphor.     

A natural hybrid of Leuciscus cephalus (L.) and Chalcalburnus chalcoides (Güldenstädt)(Osteichthyes‐Cyprinidae) from Lake Tödürge (Sivas, Turkey)

Hybridization between Leuciscus cephalus and Chalcalburnus chalcoides was identified from biometrical features in 55 fish caught from Lake Tödürge, Sivas, Turkey, between April 1994 and November 1997. The hybrid index V _h for metric and meristic characters was intermediate ( V _h = 45·6) compared with their parents ( L. cephalus V _h = 0 or negative and C. chalcoides V _h ≥ 100). Morphological, metric and meristic features of L. cephalus  ×  C. chalcoides also resembled those of the parents. The majority presented an intermediate position which was best shown by the shape of mouth, caudal fin, gill rakers and pharyngeal teeth, and also by the caudal peduncle depth, head and interorbital width, predorsal and preanal distance, height of anal fin, length of anal base and other characters.     

Translocation (3;12) (p21-pter; q24.1-qter) and phenylketonuria

Cytogenetic karyotyping in mental retardation associated with physical dysmorphism has been regarded as the primary key for the classification of syndromes and other genetic disorders for the predisposition of neoplasia and other fatal diseases. Giemsa-banding of metaphase chromosomes in lymphocytes is a traditional and routine process for the identification of the chromosomal counterpart which can provide a clue for molecular investigation in the subject. An 8-year-old girl showed a diploid karyotype 46, XX, t(3;12) (p21-pter, q24.1-qter) in peripheral blood lymphocyte culture. Biochemical examination of urine labelled her as a case of phenylketonuria. The maternal karyotyping was similar and confirmed the maternal transmission of the translocation.     

Antimicrobial components of haemolymph and exosecretion of larvae <Emphasis Type="Italic">Lucilia sericata</Emphasis> (Meigen) (Diptera,Calliphoridae)

The present study deals with molecular nature and peculiarities of the functioning of two main protective systems of larvae Lucilia sericata—the antimicrobial compounds of haemolymph and exosecretion released by feeding larvae into environment. In the haemolymph of larvae undergone to bacterial infestation, the chromato-masspectrometry methods identified a set of inducible antibacterial peptides including defensins (3844, 4062, and 4117 Da), P-peptide (3043 Da), and four new polypeptides (3235, 3702, 3746, and 3768 Da). The exosecretion of Lucilia sericata maggots contains the peptides analogous or identical to the haemolymph antimicrobial peptides (diptericins: 8882 Da and 9025 Da), high molecular compounds of the peptide nature (6466 Da, 6633 Da, 5772 Da, 8631 Da, etc.) differing from the known haemolymph components, and the low molecular compounds (130–700 Da). The spectrum of exosecretion bactericidal activity includes the representatives of various groups of bacteria including pathogen the most actual from the medical point of view-the methicillin-resistant Staphylococcus aureus that does not have anti-staphylococcal activity in contrast to haemolymph. The exosecretion components suppressing growth and development of this staphylococcus represent the substances of low molecular mass (from 160 to 1020 Da). The performed studies characterize the strategies used by “surgical maggots” for protection from pathogens and for suppression of microbial competitors, and allow better understanding of molecular mechanisms of larval therapy of purulent infectious diseases. These studies in perspective can serve the basis for creation of the principally new drugs for struggle with usual and antibiotics-resistant bacterial infections.     

Identification of interleukin‐16 (IL‐16) and interleukin‐17D (IL‐17D) genes from Dabry's sturgeon (Acipenser dabryanus)

Dabry's sturgeon (Acipenser dabryanus) represents an ancient Actinopterygian lineage that are termed “living fossils”. Many diseases have been found in Dabry's sturgeon. In the present study, genes encoding interleukin (IL)‐16 and IL‐17D in Dabry's sturgeon were identified by RNA‐sequencing. Phylogenetic tree analysis suggested that they clustered together with the corresponding pro‐IL‐16 proteins and IL‐17D proteins from other fish. Sequence analysis revealed that IL‐17D protein was more conserved than pro‐IL‐16. Dabry's sturgeon pro‐IL‐16 contains four putative PDZ domains and do not include signal peptides, while IL‐17D only possesses signal peptides (1–25 aa). The expression patterns of IL‐16 and IL‐17D genes were investigated in Dabry's sturgeon to reveal their functions in disease. The expression level of IL‐16 showed no significant changes in embryos; however, the high expression level of IL‐17D at 0–14 hpf (hours post fertilization) implied the existence of maternal expression in the oocyte and an association with embryonic development. Tissue distribution analysis revealed that IL‐16 and IL‐17D proteins have potential functions in immune and non‐immune tissue compartments. IL‐16 and IL‐17D had different fold changes in primary spleen leukocytes after polyinosinic:polycytidylic acid (poly I:C) and lipopolysaccharide (LPS) administration, which suggested that IL‐16 has a stronger antiviral capability compared with its antibacterial response, and IL‐17D has a stronger antibacterial capability compared with its antiviral response. IL‐16 showed an earlier response to virus compared with IL‐17D, and IL‐17D showed earlier and shorter response to bacteria compared with IL‐16. Our findings suggested the roles of IL‐16 and IL‐17D in Dabry's sturgeon, and provided the theoretical basis for the prevention and control of diseases of Dabry's sturgeon.     

Preparation and photophysical studies of copper(I) and ruthenium(II) complexes of 4,4′-bis(3,5-dimethoxyphenyl)-6,6′-dimethyl-2,2′-bipyridine

We report the synthesis of a new ligand, 4,4′-bis(3,5-dimethoxyphenyl)-6,6′-dimethyl-2,2′-bipyridine, optimised for binding to copper(I) and with pendant functionality that can eventually be developed into metallodendritic structures. The synthesis and photophysical properties of complexes with copper(I) and ruthenium(II) are reported. The solid state structure of the complex [Cu(1)₂][PF₆] · MeCN (1 = 4,4′-bis(3,5-dimethoxyphenyl)-6,6′-dimethyl-2,2′-bipyridine) is also described.     

Synthesis and characterization of Os(II)(dpop′) (dpop′ = dipyrido(2,3-a;3′,2′-j)phenazine) complexes with 2,2′-bipyridine(bpy); 2,2′-bipyrimidine(bpm) and 2,3-bis(2-pyridyl)pyrazine(dpp)

New Os(II) complexes including [Os(dpop′)₂](PF₆)₂ (dpop′= dipyrido(2,3-a;3′,2′-j)phenazine) and a series of mixed ligand [Os(dpop′)(N-N)Cl]PF₆ (N-N = 2,2′-bipyridine(bpy); 2,2′-bipyrimidine(bpm) and 2,3-bis(2-pyridyl)pyrazine(dpp)) were synthesized. The Os dπ → dpop′ π^∗ MLCT transitions for [Os(dpop′)₂]²⁺ are observed at lower energy than for Os dπ → tpy π^∗ (tpy = 2,2′:6′,2″-terpyridine) and Os dπ → tppz π^∗ (tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine) (The ligand abbreviations tpd, tpp and tpypz have also appeared in the literature for 2,3,5,6- tetrakis(2-pyridyl)pyrazine in addition to tppz.) MLCT transitions in the comparative [Os(tpy)₂]²⁺ and [Os(tppz)₂]²⁺ complexes. The Os dπ → dpop′ π^∗ MLCT transitions are observed at lower energy in mixed bidentate ligand N-N systems compared with [Os(dpop′)₂]²⁺. Cyclic voltammetry shows more positive osmium oxidation, and less negative ligand reduction potentials for [Os(dpop′)₂]²⁺ as compared to [Os(tpy)₂]²⁺ and [Os(tppz)₂]²⁺ complexes. The osmium oxidation potentials in mixed ligand [Os(dpop′)(N-N)Cl]⁺ complexes are at less positive potential than for the [Os(dpop′)₂]²⁺ ion. NMR results show different chemical shifts for ring protons either trans or cis to dpop′ in mixed ligand systems, and also show two geometrical isomers for the [Os(dpop′)(dpp)Cl]⁺ complex. The [Os(dpop′)(dpp)Cl]⁺ geometric isomer with the pyrazine ring of dpp trans to dpop′ is found more predominate by 1.0/0.7 over the isomer with the pyrazine ring of dpp cis to dpop′ and that inter-conversion of geometric isomers does not occur in room temperature solution on the NMR timescale.