79495-97-9

The cytotoxicity of dialkylated lariat ethers has been previously attributed to their ionophoric properties. Herein, we provide evidence that these effects are due to loss of membrane integrity rather than ion transport, a finding with important implications for the future design of synthetic ionophores.

Bibracchial (two-armed) 4,13-diaza-18-crown-6 lariat ether and tris(macrocycle) hydraphile synthetic amphiphiles alter root morphology in Arabidopsis thaliana plants. The effect on root structure and growth depends both on the hydraphile spacer chain length and lariat ether side chain length as well as the concentration of compound in the growth medium. In some cases a correlation to ion transport activity was apparent, but such a correlation is not always manifested. Surprisingly, planar bilayer conductance (BLM) studies showed that lariat ethers and lariat ether amides both exhibited well controlled membrane activity. Pore formation in soybean asolectin membranes occurred readily and the pores were stable and sustained. Low concentrations of active hydraphiles and lariat ethers altered the primary:lateral root density ratio, generally increasing it. The transporter-mediated alterations in lateral root density were suggestive of the activity of plant auxins such as indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid, which are known to depend on cytosolic potassium ion concentrations. The hypothesis that the compounds interfere with the auxin pathway was tested and discounted by using auxin-resistant A. thaliana mutants. Rather than functioning directly as auxin mimics, ionophores affect the ion gradients producing an auxin-like effect on root development.

The disclosure provides a method for increasing the lateral root development of a plant by exposing said plant to a composition containing a synthetic amphiphile. By increasing the number of lateral roots, the surface area of the root structure is increased, making the plants better able to survive such stresses as drought or low nutrients

Derivatives of aza-12-crown-4, aza-15-crown-5, aza-18-crown-6, 1,10- diaza-18-crown-6 and 1,4,8,12-tetraazacyclopentadecane with partially fluorinated substituents attached to nitrogen are prepared. Their efficiencies and selectivities in alkali metal and

A new, two-step method for the synthesis of 4,10-diaza-15-crown-5 and 4,13-diaza-18-crown-6 and their N,N'-disubstituted derivatives from bis(secondary amines) and 1,2-bis(2-iodoethoxy)ethane is described.Essentially, the method utilizes the incipient sidearms as nitrogen-protecting groups prior to cyclization.The yields for cyclization are high, ranging from 32percent to 77percent.The N,N'-disubstituted derivatives of 4,10-diaza-15-crown-5 produced by alkylation or acylation (A), acylation followed by reduction (AR), cyclization (C), hydrogenolysis (H), or single-step cyclization (O) have the following sidearms: H (H, 91percent), MeOCH2CH2 (C, 38percent), EtOCOCH2 (A, 62percent), PhCH2 (C,72percent), 2-MeOPh (C, 52percent), 2-furanylmethyl (C, 67percent), and 2-nitrobenzyl (A, 50percent).N,N'-Dibenzyl-4,10-diaza-18-crown-6 was obtained by cyclization in 63percent yield.The N,N'-disubstituted derivatives of 4,13-diaza-18-crown-6 produced with the new method have the following sidearms: H (H, 92percent), CO-Et (A, 100percent), n-propyl (AR, 78percent), n-butyl (C, 77percent), n-hexyl (C, 32percent; A, 50percent; O, 7percent), n-octyl (AR, 45percent), CO-n-heptyl (A, 71percent), n-nonyl (O, 11percent;A, 45percent;AR, 39percent), CO-n-undecyl (A, 87percent), n-tetradecyl (AR, 26percent), CO-n-tridecyl (A, 78percent), n-hexadecyl (A, 25percent), n-octadecyl (AR, 60percent), CO-n-heptadecyl (A, 100percent), allyl (O, 26percent), propargyl (O, 22percent), HOCH2CH2 (O, 28percent), MeOCH2CH2 (C, 43percent; AR, 76percent), HOCOCH2 (hydrolysis, 81percent), EtOCOCH2 (A, 92percent), PhCH2 (O, 29percent;C, 66percent), 2-furanylmethyl (O, 27percent, C, 62percent), 2-hydroxybenzyl (A, 85percent), 2-methoxybenzyl (O, 30percent), 2-cyanobenzyl (A, 95percent), 2-nitrobenzyl (A, 90percent), 3-nitrobenzyl (A, 95percent), and 4-nitrobenzyl (A, 70percent).The new cyclization method is compared with other, previously published cyclization reactions with respect to overall yield and ease of purification.When this new cyclization cannot be used, diaza crown ethers can be prepared by alkylation of 4,10-diaza-15-crown-5 or 4,13-diaza-18-crown-6.The homogeneous equilibrium cation binding constants (log Ks) have been determined in anhydrous methanol solution for many of the compounds described herein with Na+, K+, and Ca+.The cation selectivities are rationalized in terms of polar, structural, and lipophilicity effects.