RESUMO
Heteroatomic bridged paracyclophanes were obtained by two independent synthetic approaches. The required precursors consist of para R2SiCl (R = Me, iPr) substituted aromatic rings (2 and 4). They were subsequently functionalised by using NH3, [LiPH2(dme)] or LiAl(PH2)4. In the case of the Me-substituted species 2, the reaction with NH3 directly yielded the Si2N bridged paracyclophane 5. The Si2P incorporated derivative 10 was obtained by lithiation of p-C6H4(SiiPr2PH2)2 (9) and subsequent salt metathesis with the chlorosilane 4. The second approach involves the use of GaEt3 in the formation of four membered (GaPn)2 cycles (Pn = N, P). p-[C6H4{SiiPr2N(H)GaEt2}2]2 (11) and p-[C6H4{SiiPr2P(H)GaEt2}2]2 (12) represent the first examples of stable (GaPn)2cis isomers as the trans species did not appear in solution. Although 11 and 12 show a similar coordination pattern, they differ in the orientation of the aromatic systems: in the solid structure, 11 adopts a - for paracyclophanes so far unique - T-shape conformation of the phenyl rings, while 12 shows the predominant coplanar orientation. All cyclophanes were characterized by X-ray diffraction, elemental analysis, NMR and IR spectroscopy.
RESUMO
We evaluated the relationship between the presence of adrenergic nerves and the presence of alpha-1 adrenoceptors (alpha-1 AR) in the arterial tree of the rat. The thoracic aorta and the carotid, mammary, renal and femoral arteries were isolated from 20-week-old male WKY rats, along with the superior mesenteric artery and small (first order) and resistance-sized (third order) side branches of this vessel. Norepinephrine content ([NE]) and specific binding of 300 pM [3H]prazosin were determined. To estimate the total density of alpha-1 AR ([alpha-1 AR]) as well as the density of alpha-1A AR ([alpha-1A AR]), binding experiments were performed with and without pretreatment of the preparations with the irreversible alpha-1B AR and alpha-1D AR antagonist chloroethylclonidine and in the absence and presence of the alpha-1A AR selective ligand (+)-niguldipine (30 nM). Also the presence of mRNA for alpha-1A AR was evaluated by use of reverse transcriptase-polymerase chain reaction (RT-PCR). In intact rats, arterial [NE] ranged between 0.1 and 15 ng/microgram DNA, arterial [alpha-1 AR] ranged between 12.4 and 46.8 fmol/mg protein and [alpha-1A AR] ranged between 0.05 and 27.9 fmol/mg protein. There was no significant correlation between [alpha-1 AR] and [NE]. However, with respect to the [alpha-1A AR] a significant correlation between [NE] and [alpha-1A AR] was observed. RT-PCR analysis confirmed the expression of alpha-1A AR in the densely innervated mesenteric resistance-sized arteries. Two weeks after chemical sympathectomy of the rats with 6-hydroxydopamine (i) arterial [NE] was markedly reduced, and (ii) a distinct reduction in the [alpha-1A AR] as percentage of the total [alpha-1 AR] density in mesenteric artery side branches was noted. These findings indicate that there is a positive and reversible relationship between the presence of adrenergic nerves and that of alpha-1A AR in rat arteries.
