Sn12O8(OH)4(OEt)28(HOEt)4: an additional member in the family of dodecameric oxo clusters.

A tin(IV) oxoalkoxo cluster with unprecedented architecture has been prepared and characterized by single-crystal X-ray diffraction. The cluster obeys the formula Sn 12O 8(OH) 4(OEt) 28(HOEt) 4 (1) and is based on an elongated centrosymmetric assembly of 12 six-coordinate tin centers, 28 peripheral ethoxy groups (terminal and bridging), 8 oxo bridges (mu2 and mu3), 4 hydroxy bridges (mu2), and 4 ethanol molecules that are all bound to tin atoms and interact strongly, through hydrogen bonds, with an ethoxy group located on a vicinal tin atom. This compound has also been fully characterized in solution by multinuclear 1D and 2D NMR, with all of its (119)Sn, (1)H, and (13)C NMR resonances assigned with respect to the structure. Altogether, the data allowed unambiguous location of the hydroxy groups. Information on the exchange of the ethoxy groups is also presented.

Novel infinite three-dimensional network of neutral fullerene molecules in (C60)8(twin-TDAS)6

The crystal structure of (C60)8(twin-TDAS)6 [twin-TDAS = C4S6N4 = 3,3',4,4'-tetrathiobis(1,2,5-thiadiazole)] has been redetermined at low temperature in the correct space group [I23, a = 18.849 (1) A]. Structural analysis reveals a novel three-dimensional close-contact network of C60 molecules with tetrahedral holes similar to pristine C60.

The geometry and structural properties of the 4,8,12-trioxa-4,8,12,12c-tetrahydrodibenzo

The geometry of the 4,8,12-trioxa-4,8,12,12c-tetrahydrodibenzo[cd,mn]pyrene system in the cationic state was established by X-ray structural resolution of the salts formed between the cation and various anions. The geometry was found to be planar for the 4,8,12-trioxa-4,8,12,12c-tetrahydrodibenzo[cd,mn]pyrenylium and 2,6,10-tri(tert-butyl)-4,8,12-trioxa-4,8,12,12c-tetrahydrodibenzo[cd,mn]pyrenylium cations with the monovalent anions I(-), BF(4)(-), PF(6)(-), AsF(6)(-), HNO(3).NO(3)(-) and CF(3)SO(3)(-), and the divalent anions S(2)O(6)(2-) and Mo(6)Cl(14)(2-). The salts were found to crystallize in distinct space groups following a characteristic pattern. Mixed cation-anion stacking resulted in space groups with high symmetry: Pbca in three cases and R3;c in one; a temperature study of the latter was made at ten different temperatures. The formation of dimers of anions and cations resulted in lower-symmetry space groups, mainly monoclinic (P2(1)/n, P2(1)/c and C2/c), but also P1;.

Effects of a potassium channel opener (SDZ PCO 400) on guinea-pig and human pulmonary airways.

1. SDZ PCO 400 evoked dose-related relaxation of isolated airway smooth muscle. For human bronchus precontracted by endogenous tone or addition of carbachol (10(-5) M), IC50 values were 1.74 microM and 1.82 microM respectively. With guinea-pig trachea contracted by endogenous tone, a comparable IC50 (1.79 microM) was observed, but no IC50 (less than 100 microM) could be determined following contraction by carbachol (10(-6) M). 2. Airway obstruction induced by intravenous bombesin in the anaesthetized ventilated guinea-pig was diminished by intravenous injection of SDZ PCO 400 (ID50 54 micrograms kg-1) or by introduction into the duodenum (ID50 1.0 mg kg-1). Inhalation of nebulized SDZ PCO 400 (0.1 mg kg-1) diminished airway obstruction due to intravenous injection of histamine (3.2-5.6 micrograms kg-1) for up to 20 min. 3. Increased bronchoconstrictor responses to bombesin (180-240 ng kg-1) following intravenous infusion of platelet activating factor (PAF) or (+/-)-isoprenaline, or to histamine (1.0-3.2 micrograms kg-1) following intravenous injections of immune complexes, were suppressed following concomitant intravenous infusion of SDZ PCO 400 (ID50 0.3 mg kg-1 h-1, 1.0 mg kg-1 h-1 and 0.1 mg kg-1 h-1 respectively). 4. Intravenous injection of SDZ PCO 400 (0.1 mg kg-1) effected transient (less than 10 min) inhibition of histamine-induced bronchospasm, yet diminished, for prolonged periods [up to 40 min] the enhanced bronchoconstrictor responses to histamine that followed intravenous injections of immune complexes.The capacity of SDZ PCO 400 to resolve such established airway hyperreactivity was prevented by prior intraduodenal instillation of a potassium channel antagonist, glibenclamide (30 mg kg-').5. In sensitized guinea-pigs, SDZ PCO 400 inhaled as a dry powder (5.7 mg kg-') suppressed development of allergic airway hyperreactivity to histamine (1.8-3.2;pg kg-', i.v.), but failed to diminish accumulation of eosinophils or other inflammatory cells within the airway lumen 24 h after inhalation of ovalbumin.6. Preincubation (30 min) of isolated sensitized trachea of guinea-pig with SDZ PCO 400 (10-5-10-4M) did not influence contractile responses to ovalbumin. However in anaesthetized sensitized guinea-pigs,insufflation of SDZ PCO 400 (1.25 mg) as a powder substantially diminished airway obstruction that followed inhalation of ovalbumin. This effect was prevented by prior vagal section.7. It is concluded that SDZ PCO 400 reduces airway obstruction not only through direct actions on airway smooth muscle but also by impairing the expression of airway hyperreactivity, without directly influencing inflammatory events in the airways.

Development of airway hyperreactivity in the guinea-pig following allergic reactions.

It has been reported previously that acute allergic reactions in the anaesthetized guinea-pig do not evoke changed airway reactivity to histamine, animals sensitized to ovalbumin in aluminum hydroxide and exposed to allergen intravenously or by inhalation develop increased responsivity to histamine that persists for several hours. Animals that have been sensitized passively, by intravenous injection of antibody and exposed to allergen by intravenous injection, or which receive freshly prepared immune complexes by intravenous injection develop comparable airway reactivity.

Airway eosinophilia and airway hyperreactivity are parallel rather than sequential events in the guinea-pig.

It is known that eosinophil activation in the airways is associated with epithelial damage in both guinea-pigs and man and it has been presumed that airway hyperreactivity arises in consequence of these events. However, infusion of (+/- )isoprenaline induces airway hyperreactivity in the guinea-pig despite a reduction of eosinophil numbers in the airway lumen, whilst rh-GM-CSF or rh-IL3 induce eosinophilia of the airways without attendant airway hyperreactivity. These findings complement earlier studies which showed that airway hyperreactivity in sensitized animals reacting to inhaled allergen could not be correlated with the number of eosinophils in the airway lumen.

Eosinophil accumulation in pulmonary airways of guinea-pigs induced by exposure to an aerosol of platelet-activating factor: effect of anti-asthma drugs.

1. Exposure of guinea-pigs to aerosols of platelet activating factor (PAF) (0.01 to 100 micrograms ml-1) induced a dose-dependent increased incidence of eosinophils in bronchoalveolar lavage fluid (BAL) at 48 h. Total leucocyte numbers and the percentages of lymphocytes and neutrophils were unchanged in BAL fluid. 2. Increased numbers of eosinophils were detected in BAL 1 h after exposure to PAF but eosinophilia was not maximal until 48 h. One week after exposure to PAF, the percentage of eosinophils in BAL was within the normal range. 3. Depletion of circulating platelets or neutrophils by intravenous injection of specific antisera did not modify accumulation of eosinophils in the airway lumen following inhalation of PAF (10 micrograms ml-1). 4. PAF-induced pulmonary airway eosinophil accumulation was inhibited by treatment with SDZ 64-412, a selective PAF-antagonist, whether the compound was administered before, or 30 min after, inhalation of PAF. 5. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was inhibited by prior treatment with aminophylline, cromoglycate, ketotifen, dexamethasone and AH 21-132. 6. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was not inhibited by prior treatment with indomethacin, salbutamol or mepyramine.

Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs.

Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma.

Pharmacological evaluation of prophylactic anti-asthma drugs by reference to the pathological sequelae of exposure to allergen or platelet activating factor.

Exposure of guinea-pigs to platelet activating factor (PAF) induces airway hyperreactivity and causes an influx of eosinophils into the airways. These effects are inhibited by the established prophylactic anti-asthma drugs; cromoglycate, aminophylline, glucocorticosteroids and ketotifen, whereas other drug categories, with the exception of PAF-receptor antagonists, are ineffective.