2389-06-2Relevant academic research and scientific papers
NMR-based molecular ruler for determining the depth of intercalants within the lipid bilayer. Part III: Studies on keto esters and acids
Afri, Michal,Alexenberg, Carmit,Aped, Pinchas,Bodner, Efrat,Cohen, Sarit,Ejgenburg, Michal,Eliyahu, Shlomi,Gilinsky-Sharon, Pessia,Harel, Yifat,Naqqash, Miriam E.,Porat, Hani,Ranz, Ayala,Frimer, Aryeh A.
, p. 105 - 118 (2015/02/19)
The development of "molecular rulers" would allow one to quantitatively locate the penetration depth of intercalants within lipid bilayers. To this end, an attempt was made to correlate the 13C NMR chemical shift of polarizable "reporter" carbons (e.g., carbonyls) of intercalants within DMPC liposomal bilayers - with the polarity it experiences, and with its Angstrom distance from the interface. This requires families of molecules with two "reporter carbons" separated by a known distance, residing at various depths/polarities within the bilayer. For this purpose, two homologous series of dicarbonyl compounds, methyl n-oxooctadecanoates and the corresponding n-oxooctadecanoic acids (n = 4-16), were synthesized. To assist in assignment and detection several homologs in each system were prepared 13C-enriched in both carbonyls. Within each family, the number of carbons and functional groups remains the same, with the only difference being the location of the second ketone carbonyl along the fatty acid chain. Surprisingly, the head groups within each family are not anchored near the lipid-water interface, nor are they even all located at the same depth. Nevertheless, using an iterative best fit analysis of the data points enables one to obtain an exponential curve. The latter gives substantial insight into the correlation between polarity (measured in terms of the Reichardt polarity parameter, ET(30)) and penetration depth into the liposomal bilayer. Still missing from this curve are data points in the moderate polarity range.
NMR-based molecular ruler for determining the depth of intercalants within the lipid bilayer. Part IV: Studies on ketophospholipids
Afri, Michal,Alexenberg, Carmit,Aped, Pinchas,Bodner, Efrat,Cohen, Sarit,Ejgenberg, Michal,Eliyahu, Shlomi,Gilinsky-Sharon, Pessia,Harel, Yifat,Naqqash, Miriam E.,Porat, Hani,Ranz, Ayala,Frimer, Aryeh A.
, p. 119 - 128 (2015/02/19)
In our companion paper, we described the preparation and intercalation of two homologous series of dicarbonyl compounds, methyl n-oxooctadecanoates and the corresponding n-oxooctadecanoic acids (n = 4-16), into DMPC liposomes. 13C NMR chemical shift of the various carbonyls was analyzed using an ET(30) solvent polarity-chemical shift correlation table and the corresponding calculated penetration depth (in A?). An iterative best fit analysis of the data points revealed an exponential correlation between ET(30) micropolarity and the penetration depth (in A?) into the liposomal bilayer. However, this study is still incomplete, since the plot lacks data points in the important area of moderately polarity, i.e., in the ET (30) range of 51- 45.5 kcal/mol. To correct this lacuna, a family of ketophospholipids was prepared in which the above n-oxooctadecanoic acids were attached to the sn-2 position of a phosphatidylcholine with a palmitic acid chain at sn-1. To assist in assignment and detection several derivatives were prepared 13C-enriched in both carbonyls. The various homologs were intercalated into DMPC liposomes and give points specifically in the missing area of the previous polarity-penetration correlation graph. Interestingly, the calculated exponential relationship of the complete graph was essentially the same as that calculated in the companion paper based on the methyl n-oxooctadecanoates and the corresponding n-oxooctadecanoic acids alone. The polarity at the midplane of such DMPC systems is ca. 33 kcal/mol and is not expected to change very much if we extend the lipid chains. This paper concludes with a chemical ruler that maps the changing polarity experienced by an intercalant as it penetrates the liposomal bilayer.
9-Oxooctadeca-10,12-dienoic acids as Acetyl-CoA carboxylase inhibitors from red pepper (Capsicum annuum L.)
Watanebe, Jun,Kawabata, Jun,Kasai, Takanori
, p. 489 - 493 (2007/10/03)
A methanol extract of red pepper showed potent acetylCoA carboxylase inhibitory activity. The active principles were isolated and identified as (E, E)- and (E, Z)-9-oxooctadeca-10,12-dienoic acids by instrumental analyses. The IC50 values of the compounds were 1.4 x 10-6 and 1.5 x 10-6 M, respectively, their activity being nearly sixty-times higher than that of the common fatty acids themselves. A comparative study of the structure-activity relationship among their related compounds showed that the inhibitory activity was influenced neither by the position and species of the oxygen functional group in the middle of the alkyl chain nor by the configurations of the double bonds. However, it was found that the presence of double bonds between the terminal carboxyl and the mid-chain oxygen functional group lowered the inhibitory activity which could be recovered by hydrogenation of the double bonds.
SYNTHESIS OF 12- AND 13-HYDROXYSTEARIC ACIDS FROM 1,5,9-CYCLODODECATRIENE
Zakharkin, L. I.,Guseva, V. V.,Churilova, I. M.,Maskaev, A. K.,Kobilinskaya, I. F.,Tanchuk, Yu. V.
, p. 1534 - 1536 (2007/10/02)
A method was developed for the synthesis of 12-hydroxystearic acid on the basis of the reaction of 11-cyanoundecanal and 11-cyanoundecadienal, obtained from 1,5,9-cyclododecatriene and cyclododecene, with C6H13MgCl followed by alkaline hydrolysis of the nitrile group. 13-Hydroxystearic acid was obtained by hydrogenation of 13-oxostearic acid, which was synthesized from 1-N-morpholinocyclododecene and caproyl chloride.
