Resorcinarenes with 2-benzimidazolone bridges: Self-aggregation, self-assembled dimeric capsules, and guest encapsulation

Abstract

The synthesis and spectroscopic characterization of self-assembled dimeric resorcinarenes 1a–d containing four 2-benzimidazolone (cyclic urea) bridges are reported. The nanometer-size capsules are held together by a cyclic array of complementary hydrogen bonds. Unlike the related imide-bridged resorcinarenes reported by Rebek and coworkers [Heinz, T., Rudkevich, D. M. & Rebek, J., Jr. (1998) Nature (London) 394, 764–766], these strongly bound dimers aggregate in chloroform solutions yielding different self-organized structures, depending on the nature and length of the four carbon chains attached at the bottom of each resorcinarene platform, as revealed by transmission electron microscopy. Thus, phenethyl groups (dimer 1c⋅1c) produce long fibers, probably arising from tail to tail contacts and subsequent threading of the resulting linear self-assembled polymers, whereas long alkyl chains (dimers 1a⋅1a and 1b⋅1b) induce formation of large reverse vesicles of 0.8–2.2 μm diameter through side to side extensive stacking. Presumably, the rigidity of the dimer precludes folding of the aggregate into smaller vesicles. On the contrary, dimer 1d⋅1d, containing four nine-carbon chains and a cis-double bond, does not substantially aggregate and gives rise to reasonably resolved ¹H NMR spectra. The compound was shown to be dimeric either by matrix-assisted laser desorption ionization–time-of-flight and vapor pressure osmometry. Encapsulation studies were followed by NMR. Propionic or pivalic acid was included in the capsules, probably as head to head hydrogen-bonded dimers in mesitylene-d₁₂, a solvent too big to be a guest by its own. Longer dimeric carboxylic acids or larger substrates, like 2-adamantyl azide or cyclohexylcarbodiimide, do not encapsulate, but mixtures of a long and a short carboxylic acid (i.e., propionic-adamantyl or propionic-cyclohexyl) yield pairwise complexes.

Since the advent in 1993 of the so-called tennis ball, a molecular capsule held by complementary hydrogen bonds (1), developments in the field have been impelled toward larger and more robust assemblies, like soft balls (2) and related cavities (3, 4). Among these, cone-shaped calix[4]arenes (5, 6) or calix[6]arenes (7) endowed with urea functions at the wider rim have been extensively studied as self-assembling subunits, because they are semirigid and substantially preorganized. In these scaffolds, two hydrogen donors from the same urea function are linked to a single carbon atom of another urea moiety (Fig. 1). Alternatively, cyclic ureas, such as 2-benzimidazolone, interact in a geometrically more efficient way by using hydrogen donors from two different urea functions (8, 9). This result prompted us to design self-assembling resorcinarenes 1 bridged by four cyclic ureas. It is well known from the pioneering work of Cram and coworkers (10) that resorcinarenes bridged with aromatic rings can adopt a cylindrical vase or a flattened kite conformation. In the cylindrical vase conformation, the four ureas of 1 are at the right distance to interact rim to rim with ureas from another cavitands, resulting in a dimer 1⋅1 stabilized by a cyclic array of hydrogen bonds. Any alternative head to head arrangement of the monomers, other than the cyclic array, is unlikely for such cavitands in vase conformation: partial contacts involving only one or two ureas from each monomer would yield to polymeric aggregates with a substantial amount of free space and an almost orthogonal orientation of the edges of the monomer, with loss of complementary contacts.

Figure 1.

Hydrogen-bonded network present in calixarene ureas and 2-benzimidazolone, and chemical formulae of resorcinarenes 1 (with 2-benzimidazolone bridges) and 2 (with pyrazine-2,3-dicarboxylic acid imide bridges). Arrows indicate hydrogen-bonding patterns for donors and acceptors.

A related head to head cyclic array of hydrogen bonds can be obtained by using the cyclic imide scaffold 2, which gives rise to a capsule 2⋅2 of similar shape and dimensions as 1⋅1 but involves somewhat less robust, bifurcated hydrogen bonds. The synthesis and spectroscopic characterization of 2⋅2 have been recently described by Rebek and coworkers, showing remarkable encapsulation capabilities, like pairwise complexation of two different guests (11) or stabilization of reactive species, such as dibenzoyl peroxide (12). Both capsules 1⋅1 and 2⋅2 are of nanometer dimensions (about 1.0 × 1.8 nm) (Fig. 2), with an available space inside estimated as 5.7 × 14.7 Å (error ± 0.2 Å) (12).

Figure 2.

Side view of an energy-minimized (Amber force field) stick structure of resorcinarene cylindrical capsule 1⋅1 of about 1.0 × 1.8 nm dimensions showing the hydrogen-bonding network (red dashed lines). For clarity, long chains have been truncated into methyl groups, and CH hydrogen atoms have been omitted.

We describe here the synthesis and association properties of urea-containing resorcinarenes 1a–d (Fig. 3), differing in their four hydrophobic tails at the narrow rim: 1a–c contain linear residues, so the resulting capsules can aggregate side by side or tail to tail, promoting self-organization, whereas 1d is endowed with a cis-double bond that causes the tails to be bent and difficult lateral aggregation. This system was used for encapsulation studies of carboxylic acid dimers and heterodimers inside.

Figure 3.

Synthetic scheme for the preparation of resorcinarene tetraureas 1a–d from octols 3a–3d. See text for reagents and conditions.

Materials and Methods

General.

¹H and ¹³C NMR spectra were recorded on Bruker AC-200 or AMX-300 spectrometers. Chemical shifts (δ) are expressed in ppm relative to the solvent residual peak. ¹³C NMR spectra were assigned by using distortionless enhancement by polarization transfer (DEPT) experiments. Positive fast atom bombardment (FAB+) or high-resolution FAB+ mass spectra were recorded on a VG Analytical (Manchester, U.K.) AutoSpec spectrometer by using m-nitrobenzyl alcohol as matrix or matrix-assisted laser desorption ionization–time-of-flight (Reflex 3, matrix dithranol). Flash column chromatography was performed by using silica gel (Sds, Chromagel 60 ACC, 40–60 μm). All commercially available reactants (98% purity or higher, unless otherwise stated) were used as purchased without further purification. Compounds 3a–c (13, 14) have been described. The preparation and spectra of octol 3d, octanitro cavitand 4d, and octaamines 5a–d are described in the supporting information, which is published on the PNAS web site, www.pnas.org.

For the transmission electron microscopy (TEM) experiments, samples were dissolved in organic solvents, deposited on carbon grids, and the solvents were allowed to evaporate. The grids were then negatively stained for 1 min with a freshly prepared 2% solution of uranyl acetate. TEM was performed in a JEOL 1200EX electron microscope operated at 120 kV. Electron micrographs were obtained under minimum electron dose conditions on SO-163 film (Kodak). Micrographs were developed by using D-19 developer (Kodak) at full strength for 12 min. Vapor pressure osmometry measurements were performed in chloroform by using a Gonotec (Berlin) Osmomat 070 osmometer operated at 30°C and calibrated with benzyl.

General Procedure for the Synthesis of Tetraureas 1a–d.

1,3,19,21,27,29,35,37-Octahydro-8,10,12,14-tetraalkyl-6,16:7,15-dimetheno-2H,8H,10H,12H,14H,20H,28H,36H-benzimidazo [5′′,6′′:2′,3′ [1,4]benzodioxonino[10′,9′:5,6]benzimidazo[5′′,6′′:2′,3′]-benzimidazo[5′′′′,6′′′′:2′′′,3′′′][1,4 dioxonino[6′′′,5′′′:9′,10′[1,4] benzodioxonino [6′,5′:9,10]-[1,4]benzodioxonino[2,3-f]benzimidazole-2,20,28,36-tetrone. Et₃N [12.1 equivalent (eq)] was added to a solution of 5a–d (0.237⋅mmol) and triphosgene (4.4 eq) in tetrahydrofuran (25 ml) under argon, and the mixture was stirred for 48 h. The solvent was evaporated, and the residue was triturated in H₂O under sonication. The solid was filtered and dried. Yield about 80%. Purification: a solution of crude 1a–d (0.318 mmol) (BOC)₂O (14.8 eq), Et₃N (34.9 eq), and 4-(N,N-dimethylamino)pyridine (7.0 eq) in tetrahydrofuran (40 ml) under argon was stirred for 6 h. After evaporation of the solvent, the residue was treated with CH₂Cl₂, washed with 1 M HCl and brine, dried over Na₂SO₄, filtered, and concentrated. The residue was finally purified by flash chromatography (hexane-ethyl acetate 6:4) to give pure 6a–6d. Yield: 75–85%. Deprotection was achieved with trifluoroacetic acid in CH₂Cl₂ (2 h), evaporation, and trituration with methanol. Yield of pure 1a–d, 100%; melting point (mp), >300°C (decomposition).

Compound 1a.

¹H NMR (300 MHz, CDCl₃) δ 10.47 (s, 8H, −NH), 7.5–6.7 (br, 16H, ArH) (Ar, aryl), 5.9–5.6 (br, 4H, ArCHAr), 1.8–1.5 (br, 8H, CH₂), 1.5–1.0 (br m, 72H, CH₂), 0.82 (br t, 12H, CH₃); ¹³C NMR (75 MHz, DMSO-d₆) δ 155.9, 155.2, 146.4, 134.8, 126.3, 124.4, 116.3, 104.1, 32.9, 31.2, 29.2, 29.0, 28.7, 27.7, 22.0, 18.7, 13.7; MS (FAB+) m/z 1626.1 [M]⁺, 3252.2 (0,8%) [2M]⁺.

Octa-BOC derivative 6a.

mp 275–277°C; ¹H NMR (200 MHz, CDCl₃) δ 7.71 (s, 8H, ArH), 6.92 (s, 4H, ArH), 6.85 (s, 4H, ArH), 4.64 (t, 4H, ArCHAr), 2.1–1.9 (m, 8H; CHCH₂), 1.67 (s, 72H C(CH₃)₃), 1.28 (s, 72H, CH₂), 0.89 (t, 12H CH₃); ¹³C NMR (50 MHz, CDCl₃) δ 179.9, 153.2, 139.2, 137.3, 130.1, 127.7, 125.4, 107.0, 100.3, 35.2, 37.0, 27.0, 24.4, 23.1, 22.6, 13.8; MS (high-resolution FAB+) m/z 2426.9960 (Calcd 2426.9961) [M]⁺, 2326.8801 (Calcd 2326.8803) (85%) [M-C₅H₉O₂]⁺.

Compound 1b.

¹H NMR (300 MHz, DMSO-d₆) δ 10.15 (s, 8H, NH), 7.70 (br s, 4H, ArH), 7.58 (s, 4H, ArH), 7.38 (s, 8H, ArH), 5.49 (t, 4H, ArCHAr), 2.4–2.2 (br m, 8H, CH₂), 1.5–1.3 (br m, 8H, CH₂), 1.3–1.1 (m, 40H, CH₂), 0.83 (br t, 12H, CH₃); ¹³C NMR (75 MHz, DMSO-d₆) δ 156.3, 155.5, 146.4, 135.2, 126.8, 124.7, 117.0, 104.5, 33.1, 31.4, 29.4, 29.2, 28.9, 27.9, 22.3, 14.1; MS (FAB+) m/z 1457.6 [M]⁺, 2915.4 (0,2%) [2M]⁺.

Octa-BOC derivative 6b.

mp 289–291°C; ¹H NMR (200 MHz, CDCl₃) δ 7.70 (s, 8H, ArH), 6.91 (s, 4H, ArH), 6.85 (s, 4H, ArH), 4.66 (t, 4H, ArCHAr), 2.1–1.9 (m, 8H CHCH₂), 1.68 (s, 72H C(CH₃)₃), 1.27 (m, 56H, CH₂), 0.90 (t, 12H, CH₃); MS (FAB+) m/z 2158.5 [M − C₅H₉O₂]⁺, 2058.3 (69%) [M − 2C₅H₉O₂]⁺.

Compound 1c.

¹H NMR (300 MHz, DMSO-d₆) δ 10.14 (s, 8H, NH), 7.81 (s, 4H, ArH), 7.66 (s, 4H, ArH), 7.42 (s, 8H, ArH), 7.3–7.0 (m, 20H, ArH), 5.58 (t, 4H, ArCHAr), 2.7–2.4 (br m, 16H CH₂CH₂); ¹³C NMR (75 MHz, DMSO-d₆) δ 156.4, 155.7, 146.4, 141.9, 135.2, 128.6, 128.4, 126.9, 126.0, 124.6, 117.3, 104.5, 34.4, 33.4, 30.8; MS (FAB+) m/z 1425.9 [M]⁺, 1319.9 [M − C₈H₉]⁺.

Octa-BOC derivative 6c.

mp > 300°C; ¹H NMR (200 MHz, CDCl₃) δ 7.63 (s, 8H, ArH), 7.3–7.0 (m, 20H, ArH), 6.95 (s, 4H, ArH), 6.89 (s, 4H, ArH), 4.65 (t, 4H; ArCHAr), 2.7–2.6 (s, 8H, CH₂CH₂), 2.5–2.3 (s, 8H, CH₂CH₂) 1.64 (s, 72H, C(CH₃)₃); ¹³C NMR (50 MHz, CDCl₃) δ 181.1, 154.1, 147.1, 144.6, 141.0, 131.8, 128.4, 125.9, 123.7, 122.3, 113.7, 108.1, 85.6, 34.1, 33.8, 33.4, 28.0; MS (FAB+) m/z 1425.5 [M − 8C₅H₉O₂]⁺.

Compound 1d.

¹H NMR (300 MHz, CDCl₃) δ 10.48 (s, 8H, NH), 7.31 (br s, 4H, ArH), 7.22 s, 4H, ArH), 7.13 (s, 8H, ArH), 5.81 (br, 4H, ArCHAr), 5.6–5.3 (br, 8H, CH = CH), 2.30 (br m, 8H CH₂), 2.15 (br m, 8H, CH₂), 1.95 (br m, 8H, CH₂), 1.5–1.1 (m, 24H, CH₂), 0.96 (br t, 12H, CH₃); ¹H NMR (300 MHz, DMSO-d₆) δ 10.44 (s, 8H, NH), 7.74 (s, 4H, ArH), 7.61 (s, 4H ArH), 7.40 (s, 8H, ArH), 5.52 (br, 4H, ArCHAr), 5.5–5.2 (br, 8H, CH = CH), 2.5–2.2 (br m, 8H CH₂), 2.1–1.9 (br m, 8H CH₂), 1.9–1.7 (br m, 8H, CH₂), 1.4–1.1 (m, 24H, CH₂), 0.82 (br t, 12H, CH₃); ¹³C NMR (75 MHz, DMSO-d₆) δ 156.4, 155.7, 146.5, 135.0, 130.3, 129.2, 126.8, 124.7, 117.3, 104.6, 33.0, 31.1, 28.9, 26.8, 25.5, 22.1, 14.0; MS (FAB+) m/z 1506.0 [M]⁺, 3012.1 (2%) [2M]⁺ (matrix-assisted laser desorption ionization–time-of-flight); m/z 1505.9 (100%) [M]⁺, 3012.5 (25%) [2M]⁺.

Octa-BOC derivative 6d.

mp 278–280°C; ¹H NMR (200 MHz, CDCl₃) δ 7.71 (s, 8H, ArH), 6.93 (s, 4H, ArH), 6.82 (s, 4H, ArH), 5.5–5.2 (m, 8H, CH = CH), 4.71 (br t, 4H, ArCHAr), 2.2–2.0 (m, 16H, CH₂CH = ), 2.0–1.8 (br d, 8H, CHCH₂), 1.62 (s, 72H, C(CH₃)₃), 1.24 (s, 24H, CH₂), 0.87 (t, 12H, CH₃). ¹H NMR (200 MHz, DMSO-d₆) δ 7.63 (s, 8H, ArH), 7.42 (s, 4H, ArH), 7.01 (s, 4H, ArH), 5.4–5.1 (m, 8H, CH = CH), 4.92 (br t, 4H, ArCHAr), 2.4–2.1 (br, 8H, CHCH₂), 2.0–1.9 (m, 8H CH₂CH = ), 1.8–1.7 (m, 8H CH₂CH = ), 1.53 (s, 72H C(CH₃)₃), 1.3–1.0 (br m, 24H, CH₂), 0.89 (t, 12H, CH₃); ¹³C NMR (200 MHz, DMSO-d₆) δ 180.8, 156.4, 155.7, 146.4, 135.0, 130.3, 129.2, 126.9, 124.8, 117.3, 104.6, 33.0, 32.0, 31.1, 28.9, 26.8, 25.5, 22.1, 17.2, 14.1; MS (high-resolution FAB+) m/z 2206.6041 (Calcd 2206.6041) [M − C₅H₉O₂]⁺, 2106.4882 (Calcd 2106.4883) (73%) [M − 2C₅H₉O₂]⁺.

Results and Discussion

Synthesis.

The synthetic route fo 1a–d is outlined in Fig. 3. Conditions were as follows: for step a, octols 3a–d were O-alkylated with 1,2-difluoro-4,5-dinitrobenzene, following a modification of the procedure described by Cram et al. (15), to give octanitro derivatives 4a–d; for step b, the nitro groups were reduced to amines 5a–d with SnCl₂; and for step c, triphosgene and Et₃N, affording crude ureas 1a–d. Purification was achieved by means of the corresponding octa-BOC derivatives 6a–d (step d), which were submitted to column chromatography and then deprotected back to 1a–d by acid hydrolysis (step e).

Self-Organization of 1a⋅1a−1c⋅1c.

¹H NMR spectra of 2-benzimidazolone-bridged resorcinarenes 1a–c in CDCl₃ showed ill-resolved broad signals for all protons, which slightly sharpened after addition of some DMSO-d₆. A similar pattern was observed in more polar solvents, such as acetone-d₆, acetonitrile-d₃, or even trifluoroacetic-d₁ acid. The signals at 5.5–5.9 ppm in DMSO-d₆ for the ArCHAr methyne protons accounted for cylindrical vase conformations for all these compounds (10). Indeed, preliminary x-ray data indicate that crystals of 1c grown in DMSO are in vase conformation (K. Rissanen, unpublished results). The poorly resolved signals suggested extensive aggregation. Indeed, TEM micrographs of CHCl₃ solutions of 1a or 1b deposited in the microscope grid and left to evaporate before coating with uranyl acetate showed the formation of remarkably large vesicles (Fig. 4 a and b). Because the aggregation takes place in organic solvents, the vesicles, with the hydrophobic chains at the edges of the bilayer and the aromatic-tetrameric unit bearing the polar groups in the middle, are formally reverse vesicles. Their diameter (0.8 μm for 1a, 2.2 μm for 1b), although smaller than giant vesicles (5–200 μm), is definitely much larger than typical large unilamellar vesicles (0.1–0.2 μm) (16). The formation of such vesicles is compatible with side to side extensive stacking of the resorcinarene dimers 1a⋅1a or 1b⋅1b, their rigidity precluding folding of the aggregate into smaller spheres (Fig. 4c). Because the area occupied by each dimer (seen from the top) is roughly 160 Ų (a number consistent with preliminary compression data from Langmuir–Blodgett films), about 12.5 × 10⁶ dimers (or 25 × 10⁶ monomers) would be present in the case of resorcinarene 1b.

Figure 4.

Self-organization of resorcinarene tetraureas. TEM micrographs of reverse vesicles (a) formed by evaporation of a CHCl₃ solution of 1a and (b) 1b. (c) Cartoon representation of the structure of vesicles from 1b. (d) TEM micrograph of the fibers formed under analogous conditions from 1c.

The stability of the vesicles was assessed by dye encapsulation. Either methylene blue or rhodamine B (too large to be encapsulated inside the dimers) was easily incorporated by sonication and remained inside even after filtration and thorough washing with CH₂Cl₂.

Contrary to 1a or 1b, resorcinarene urea 1c aggregates into long fibers of about 20 nm in width (Fig. 4d) on evaporation of CHCl₃ solutions. This form of self-organization could be rationalized by tail to tail contacts between the aromatic rings of the phenethyl chains of dimer 1c⋅1c and subsequent threading of the resulting linear self-assembled polymers. Finally, TEM micrographs of an evaporated and uranyl-stained CHCl₃ solution of resorcinarene urea 1d did not reveal any aggregation. This is precisely what was expected for 1d, whose tails contain cis-double bonds that perturb lateral and linear contacts between the dimers. Therefore, this compound was used for the self-assembly and encapsulation studies.

Dimerization of 1d⋅1d.

The ¹H NMR spectra of 1d in CDCl₃ or in DMSO-d₆ showed relatively well resolved peaks for all protons. The singlet observed for the NH urea protons at δ = 10.48 ppm in CDCl₃, typical of strong hydrogen bonds, could not be taken solely as a proof for dimerization, because the signal in a more competitive solvent, like DMSO-d₆, was also strongly downfield-shifted (δ = 10.44 ppm). Furthermore, the compound was almost insoluble in methanol, where it should be monomeric.

Although high-resolution FAB+ mass spectra only revealed a dimer peak of 2% intensity, matrix-assisted laser desorption ionization–time-of-flight measurements showed peaks for the monomer and the dimer at m/z = 1505.9 and 3012.5, with 73 and 25% relative intensities. Both peaks were in agreement with the simulated isotope patterns. Finally, vapor pressure osmometry measurements gave a molecular weight of 2750 ± 198 g⋅mol⁻¹, in good agreement with the mass of the dimer.

No changes were observed in the NMR spectrum in CDCl₃ after dilution (1.66 × 10⁻³ to 2.59 × 10⁻⁵ M). Either in the solid state (KBr) or in solution (CHCl₃) the fingerprints of the IR spectra were identical. Also, concentration-independent UV-visible spectra were observed in the range 1.72 × 10⁻³ to 1.68 × 10⁻⁶ M, which translates into a dimerization constant K_dim ≥ 2.5 × 10⁵ M⁻¹.

Guest Encapsulation in 1d⋅1d.

Encapsulation of single molecules of commensurate size and shape for the capsule interior (dicyclohexyl carbodiimide, trans-4-stilbene methanol, p-[N-(p-tolyl)]toluamide, bibenzyl, or benzoyl peroxide), as well as homo- (toluene, hydrogen-bonded benzamide) or heterodimeric guests (p-xylene − benzene 1:1 mixture), has been evidenced by Rebek and coworkers for the tetraimide capsule 2⋅2 in the noncompetitive solvent mesitylene-d₁₂ (11, 12). Strongly shielded signals (δ = 0 to −4 ppm) were observed in all cases for the included guests.

The ¹H NMR spectrum of 1d⋅1d in mesitylene-d₁₂ displayed broad signals, even at 500 MHz (50°C). In contrast to the spectrum in CDCl₃, a broad multiplet at δ = 10.3–11.1 ppm was observed in this solvent for the ureas, because of incomplete encapsulation of the large molecule. Despite these limitations, carboxylic acids were added in about 15-fold excess to solutions of 1d⋅1d in mesitylene-d₁₂. A number of acids, such as propionic (Pro), pivalic (Piv), cyclohexanecarboxylic (Chx), or 1-adamantanecarboxylic (Ada) (Fig. 5a) were investigated. Pairwise encapsulation was observed when 1:1 mixtures (7.5-fold excess each) of a small and a large guest were added (i.e., Ada-Pro, Fig. 5b). Thus, significant changes in the spectrum, such as splitting of the urea signals or emerging of several singlets at negative δ values, were visible (Fig. 5 c–f). In contrast, addition of a single carboxylic acid resulted in encapsulation (shielded signals at negative δ values), but no significant loss of the symmetry of the capsule was observed.

Figure 5.

(a) Chemical formulae of some carboxylic acids used as guests in encapsulation studies with 1d⋅1d. (b) Cartoon representation of the encapsulation of a carboxylic acid heterodimer. (c–f) ¹H NMR spectra (300 MHz, 295 K, mesitylene-d₁₂, upfield region δ = 10–11.2 ppm, and downfield region δ = 0 to −5 ppm) showing encapsulation of carboxylic acids by capsule 1d⋅1d. (c) Propionic acid (Pro-Pro), (d) cycloxexanecarboxylic acid (Chx-Chx), (e) 1:1 mixture of propionic and cycloxexanecarboxylic acids (Chx-Pro), and (f) 1:1 mixture of propionic and 1-adamantanecarboxylic acids (Ada-Pro).

In conclusion, urea-bridged resorcinarenes, like their imide-bridged counterparts of similar dimensions developed by Rebek and coworkers (11, 12), self-assemble into strong dimers in organic solvents but, unlike imides, ureas endowed with long alkyl chains aggregate into very large reverse vesicles in chloroform. Phenethyl chains form filaments instead. Disrupting the linear arrangement of these chains, by means of a cis-double bond, allows a better control of the aggregation and the study of guests encapsulation. Carboxylic acids encapsulate pairwise, reflecting optimal occupancy of the cavities.

Abbreviations

Ar

aryl

BOC

tert-butoxycarbonyl

FAB

fast atom bombardment

TEM

transmission electron microscopy

eq

equivalent

mp

melting point