1090
J . A m . Chem. SOC.1989, 111, 1090-1094
J = 14 Hz), 1.50 (s, 3 H), 1.39 (s, 6 H), 1.20 (d, 1 H, J = 14 Hz); high-resolution mass spectral analysis for C,8H22N203calcd 314.1630, found 3 14.1630. Cis-Trans Imide Amide Naphthalene 9b. A solution of 75.0 mg (0.291 mmol) of 8b in 2.0 mL of CH2C12was added to an ice cold solution of 129 mg (0.901 mmol, 3.1 equiv) of 2-aminonaphthalene in 2.0 mL of CH2C12, 1.25 mL of dry pyridine, and a catalytic amount of DMAP under N2. After 1 h, the ice bath was removed and stirring continued for an additional 8 h. After workup and flash chromatography (described in 9a), 79.7 mg of product 9b (75.2% yield) was obtained as a colorless solid: mp 255-256 OC; IR, 3368, 3300, 1699, 1678, 1555, 1500 cm-I; 'H NMR 6 8.21 (s, 1 H), 7.88 (d, 1 H, J = 7 Hz), 7.79 (d, 1 H, J = 7 Hz), 7.45 (m, 3 H), 7.30 (s, 1 H), 2.15 (d, 1 H, J = 14 Hz), 2.05 (dd, 2 H, J = 7 Hz), 1.50 (m, 3 H), 1.45 (s, 3 H), 1.25 (ns, 6 H); high-resolution mass spectral analysis for C22H24N20,calcd 364.1787, found 364.1787. Cis-Trans Imide Amide Anthracene 9c. A solution of 125 mg (0.485 mmol) of 8b in 3.0 mL of CHC1, was added to a stirred solution of 103 mg (0.533 mmol, 1.1 equiv) of purified 2-aminoanthracene and a catalytic amount of DMAP in 8.0 mL of dry pyridine at room temperature. The reaction was stirred under N 2 for 10 h and then diluted with CH2C12. The solution was washed with 10% aqueous HC1 and saturated aqueous NaHCO,, dried (Na2S04),filtered, and concentrated. Purification of the product by flash chromatography on a 19-mmcolumn using 25% EtOAc in hexanes afforded 149 mg (74.1% yield) as a slightly yellow
solid: mp > 300 OC; IR, 3337,3244,3100,2924, 1670, 1550,1377 cm-I; 'H NMR 6 8.37 (d, 2 H, J = 7 Hz), 8.36 (d, 2 H, J = 7 Hz), 7.97 (dd, 2 H, J i = 7 Hz, J2 = 1 Hz), 7.26 ( s , 1 H), 2.70 (d, 1 H, J = 14 Hz), 2.04 (q, 4 H, J = 7 Hz), 1.45 (s, 3 H), 1.36 (s, 6 H), 1.35 (m, 3 H); high-resolution mass spectral analysis for C26H26N203 calcd 414.1943, found 414.1945. Cis-Trans Imide Amide Anthraquinone 9d. A solution of 96.8 mg (0.376 mmol) of imide acid chloride 8b was added to an ice cold, magnetically stirred solution of 122 mg (0.546 mmol, 1.5 equiv) of purified 2-aminoanthraquinone and a catalytic amount of DMAP in 10.0 mL of dry pyridine under N2. After 1 h, the ice bath was removed. Stirring was continued for 8 h, and then the reaction was diluted with CH2C12. The solution was washed with 10% aqueous HCI and saturated aqueous NaHCO,, dried (Na2S04),filtered, and concentrated. Purification of the product by flash chromatography on a 19-mm column using 25% EtOAc in hexanes as eluent afforded 128 mg (76.6% yield) of 9d as a slightly yellow solid: mp > 300 OC; IR, 3350, 3200, 2950, 1772, 1716, 1695 cm-'; 'H NMR 6 8.31 (m, 5 H), 8.22 (d, 1 H, J = 1 Hz), 7.83 (s, 1 H), 7.81 (m, 2 H), 7.58 (s, 1 H), 2.32 (d, 2 H, J = 14 Hz), 2.15 (d, 2 H, J = 14 Hz), 2.02 (d, 2 H, J = 14 Hz), 1.58 (s, 6 H), 1.45 (s, 3 H), 1.30 (d, 1 H, J = 14 Hz); high-resolution mass spectral analysis for C2,H2,N2O, calcd 444.1685, found 444.1685. Acknowledgment. W e a r e grateful to t h e National Science Foundation for support of this work.
Molecular Recognition with Convergent Functional Groups. 7. Energetics of Adenine Binding with Model Receptors Kevin Williams, Ben Askew, Pablo Ballester, Chris Buhr, Kyu Sung Jeong, Sharon Jones, and Julius Rebek, Jr.* Contribution f r o m the Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260. Received November 18, 1987
Abstract: The energetics of complexation for model receptors and adenine derivatives are reported. The new systems feature
Watson-Crick, Hoogsteen, and bifurcated hydrogen bonding as well as aryl stacking interactions. These factors can act simultaneously on adenine derivatives because the model receptors present cleftlike shapes which a r e complementary to the surface of adenine. The association constants vary from 50 to l o 4 M-l in solvents such as CDCI, that compete poorly for hydrogen bonds. The energetics of binding are explored as a function of receptor and guest structure, solvent, and temperature.
In the preceding paper we introduced a new type of receptor for adenine derivatives (eq 1) a n d gave evidence for structural features involved in its complexes.' T h e new systems a r e based Hydrogen
Table I. Association Constants and Degree of Saturation Observed for the Binding of 10 to the Model Receptors (CDCI,, 24 "C)
entry 1 2 3 4 5 6 7 8
9 10
11 12
1
2
on the U-shaped relationship between functional groups provided by Kemp's2 triacid 3, a feature that permits simultaneous binding through base pairing and aromatic stacking interactions. These forces converge from perpendicular directions and provide an ideal (1) B, Askew; p, Ballester; c, Buhr; K. s, Jeong; s, Jones; K , Parris; K, Williams; J. Rebek, Jr. J . Am. Chem. SOC.,preceding paper in this issue. (2) Kemp, D. S . ; Petrakis, K. S . J . Org. Chem. 1981, 46, 5140-5143.
0002-7863/89/1511-1090$01.50/0
13 14 15 16
receptor
Ka, M-'
4c 4d 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 51 5m 8c 9a 9b 9c
50 50 101 220 440 2100 120'
90 125 79 64 11000 2500 2300 206 50
66 18 54 19 59 'Uncorrected for the presence of dimer. 17
satrn, % 65 69 79 86 96 96 98 79 76 78 77 96 100 100 74 65 70 69 70
--
microenvironment for adenine derivatives. In this paper we explore t h e energetics of the binding event a s a function of structure, solvent, temperature, and substrate. 0 1989 American Chemical Society
J . Am. Chem. Soc., Vol. 1 1 1, No. 3, 1989 1091
Molecular Recognition with Convergent Functional Groups
0.003
0
"
-
I!t
D
0
0.002
X Y i
&
0
I 0
0, 0
0.001
I
10
0
20
Equivalents 01 (10) added
Figure 1. Saturation plot of 5c titrated with 10.
Synthesis. T h e synthesis of the systems involves acylation of 4b with various amines and phenols (6a-m); the isomeric derivatives 9a-d were prepared from 7 for comparison purposes (eq 2 and 3). T h e experimental details for the preparations are described in the preceding paper,' and the same numbering system for structures is used here.
0.000
0.1 0 . 2 0.3 0 . 4 0.5 0.6 0.7 0.8 0.9 1.0
Mole Fraction
Figure 2. Job plot of 5c and 10. Table 11. Self-Association (Dimerization) Constants (ea 4)
Sa X z OH Sb X i C l S c X = OMe
Oa-d
entry
receptor
1 2 3
Sa
5b 5c
entry 4
Kd, M-' 2.8 2.5 2.2
5 6
receptor
Kd,M-'
5d 5e 8c
>50 59 2.0
shift of the imide NH signal from 7.6 to > 1 3 ppm. Typical saturation data are shown in Figure 1 for the specific case of 5c and 9-ethyladenine (10) in CDCI3 a t room temperature. A J o b plot for 5c, reproduced in Figure 2, established that a 1:l stoichiometry was i n ~ o l v e d . ~Significantly, the diimides 5j and 5k gave Job plots that also showed maxima a t 0.5 mole fraction, characteristic of a 1:l complex. There are a number of problems involved in evaluating titration data of this sort (a subject well-treated by Deranleau4), and for the most part, we have wrought the data with the Eadie method.5 The association constants K, are generally in the range of %->lo3, so it is possible to observe the saturation range of 20->95% for titrations a t N M R concentrations. W e estimate (based on reproducibility) that the numbers for the association constants are only good to &lo%, even though some titrations gave results within 2% of each other. Generally, it took 30 equiv of 9-ethyladenine to reach the limiting N M R spectrum, in which the chemical shift of the imide reaches ca. 13-13.5 ppm. Even in those cases where the limit was not reached, it is still reasonable to assume that saturation results in the same chemical shift for the imide NH involved in base pairing. The value of 13.2 was used to determine the degree of saturation. Table I gives the results for the various structures. Self-association of these systems is possible since complementary hydrogen bonds can be formed in imide dimers6 (eq 4). An
Methods. Association constants were obtained by N M R titration protocols that generally involved addition of adenine derivatives 10 or l l to solutions of the imides in CDCI, or other
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.,
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