A family of 15 ferrocene derivatives has been prepared, most of which are reported for the first time. This includes FcCH2O-3-cholestanyl, 1; FcCH2O(CH2)13CH3, 2; FcCH2O(CH2)15CH3, 3; FcCH2O(CH2)17CH3, 4; FcCH2N[(CH2)17CH3]2, 5; FcCH2O(CH2)8OCH2Fc, 6; FcCH2O(CH2)12OCH2Fc, 7; FcCH2O(CH2)16OCH2Fc, 8; Fc(CH2)22Fc, 9; FcCH2-3,17-β-estradioxy-CH2Fc, 10; Fc-1,1‘-[COO(CH2)16CH3], 11; FcCONH(CH2)17CH3, 12; Fc-1,1‘-{CON[(CH2)17CH3]2}2, 13; Fc-1,1‘-(COO-3-dihydrocholesteryl), 14; and Fc-1,1‘-(COO-3-cholesteryl), 15. Redox potentials for 1−15 have been determined and are in the range 400−450 mV for 2−6 (vs SSCE) and 509 mV for 1, 972 mV for 7, 806 mV for 8, 711 mV for 9, 941 mV for 10, and 945 mV for 11 (vs Ag/AgCl). Upon oxidation with Ce(IV), aqueous suspensions of compounds 1−5 and 7−10 formed stable vesicles after sonication. The charged monomers that formed vesicles afforded aggregates in the 2000−3000 Å range that were characterized by laser light scattering and negative stain electron microscopy. In the absence of an oxidizing agent, vesicles failed to form from any of the 15 monomers even after prolonged sonication. Addition of 500 μM aqueous Na2S2O4 solution collapsed the vesicles formed from 1−5 and 7−10, and the original amphiphile monomers were detected afterward by thin layer chromatography. It was concluded from cyclic voltammetry that both ferrocene residues in 8 were oxidized. Vesicles formed from 7−10 represent the first examples of a redox-switched bolaamphiphile.

Electrospray ionization mass spectrometry (ESI-MS) was used to probe multiple cation complexation by C(12)H(25)(CH(2))(12)(CH(2))(12)C(12)H(25), 2, and <18N>CH(2)C(6)H(4)CH(2), 3. Complexation of two cations (2Na(+), 2 K(+), or Na(+) and K(+)) by 3 and three cations by 2 (3 Na(+), 3 K(+), and mixtures) as well as mixed proton-metallic cation complexes of both were observed. The K(+)/Na(+) cation-binding selectivity of 18-crown-6 was studied by ESI-MS of a methanol solution, and the selectivity profile was favorably compared with data obtained previously by ion-selective electrode techniques in the same solvent.

Ten 18-membered ring lariat ether compounds have been prepared as one-, two-, and three-armed derivatives of aza-, diaza-, and triaza-18-crown-6. They include N-[[(3-cholestanyloxy)carbonyl]methyl]aza-18-crown-6, 1, N-tetradecylaza-18-crown-6, 2, N,N‘-dibutyl-4,13-diaza-18-crown-6, 3, N,N‘-dinonyl-4,13-diaza-18-crown-6, 4, N,N‘-didodecyl-4,13-diaza-18-crown-6, 5, N,N‘-ditetradecyl-4,13-diaza-18-crown-6, 6, N,N‘-dioctadecyl-4,13-diaza-18-crown-6, 7, N,N‘-bis[[(3-cholestanyloxy)carbonyl]methyl]-4,13-diaza-18-crown-6, 8, N,N‘-bis[[(3-cholestanyloxy)carbonyl]decyl]-4,13-diaza-18-crown-6, 9, and N,N‘,N‘‘-tri-n-hexyl-4,10,16-triaza-18-crown-6, 10. Compounds 2, 8, and 9 are previously unreported. Aqueous suspensions of these monomers were sonicated, and the first evidence for stable aggregates formed from diaza and triaza lariat ethers (3−10) was obtained. The formation of aggregates from 3 or 10 is especially notable since the side chains are butyl or hexyl, respectively. The aggregates were studied by a combination of laser light scattering, electron microscopy, and dye entrapment. All of the amphiphiles proved to form aggregates thought to be vesicles except 2, which formed micelles. The similarity in sizes of the vesicles, apparently irrespective of side chain, and the general indifference of aggregate size to the presence of cations suggest that headgroup organization determines overall size in this case. Protonation of one or more macroring nitrogen atoms could lead to a hydrogen-bond network that would stabilize the aggregates and have low affinity for added cations.

The bay region epoxide of benzo[a]pyrene (anti-BPDE) alkylates DNA to form adducts with >98% trans stereochemistry. Halide ions catalyze this reaction; however, this pathway is characterized by the formation of adducts with altered cis stereochemistry. Bay region halohydrins are possible intermediates in these reactions, but are too unstable to be isolated from aqueous solutions. However, we successfully synthesized halohydrins in tetrahydrofuran (THF) by treatment of anti-BPDE with the corresponding lithium halide salt in the presence of acetic acid. Absorbance and CD spectroscopy clearly indicated the formation of chloro-, bromo-, and iodohydrins. The structure and stereochemistry of the chlorohydrin was established by NMR. Chloride addition is exclusively at the benzylic position of the epoxide, and the stereochemistry of the C-9 and -10 positions is trans. The long-wavelength absorbance band in the chloro-, bromo-, and iodohydrin is red-shifted 7, 13, and 22 nm, respectively, relative to the hydrolysis product of anti-BPDE. The ellipticity of the same absorbance band in CD spectra of enantiomerically pure halohydrins is opposite in sign compared to that of the corresponding anti-BPDE enantiomer. The relative stability of these derivatives is chlorohydrin > bromohydrin > iodohydrin. The chloro- and bromohydrins were isolated, but the iodohydrin decomposed during this manipulation. The addition of 500 mM chloride decreased the hydrolysis rate of the chlorohydrin 4-fold in 50% THF/buffer. Direct evidence for the transient formation of the iodohydrin in aqueous buffer/acetone mixtures was obtained by absorbance spectroscopy. At 1 M chloride, bromide, and iodide, alkylation of deoxyadenosine by anti-BPDE in aqueous buffer yields 85, 91, and 92% cis adducts, respectively. In the absence of halide, alkylation of deoxyadenosine in buffer by anti-BPDE, the chlorohydrin, and the bromohydrin yields 32, 65, and 83% cis adducts, respectively.

Thirty ferrocene derivatives were prepared and their ability to form vesicles in aqueous solution when oxidized was assessed. The compounds included alkyl ferrocenylmethyl ether derivatives of the form C 10 H 9 FeCH 2 OR in which R = octyl, dodecyl, tetradecyl, hexadecyl, octadecyl and eicosanyl. One single-tailed amine derivative, C 10 H 9 FeCH 2 NR 2 , R = octadecyl, was studied. Alkylferrocene derivatives had the form C 10 H 9 FeR in which R = butyl, decyl, tetradecyl, hexadecyl, octadecyl, eicosanyl and docosanyl. Sixteen symmetrical 1,1Ј-disubstituted ferrocenes were also studied. Three ethers were of the form C 10 H 8 Fe-1,1Ј-(CH 2 OR), 2 , R = tetradecyl, hexadecyl and octadecyl. Four corresponding dialkyl derivatives of the form C 10 H 8 Fe-1,1Ј-R 2 , R = decyl, tetradecyl, hexadecyl and octadecyl, were assessed. Finally, a range of 1,1Ј-disubstituted ferrocene derivatives were analyzed. These all had the form C 10 H 8 Fe-1,1Ј-(COR) 2 , for which R has the following identities: octyl, tridecyl, pentadecyl and heptadecyl (ketones); heptadecyloxy, 3-cholesteryl and 3-cholestanyl (esters); and two amides, R = NHC 18 H 37 and N(C 18 H 37 ) 2 . The alkyl and ether derivatives could be readily oxidized and formed vesicular aggregates upon sonication. The ketones, esters and amides could be oxidized but the ferricenium derivatives did not form stable aggregates. An interesting observation is that the aggregates formed were vesicular whether the ferrocene derivative had one or two alkyl tails.