Solid-Phase Synthesis and Combinatorial Technologies

a:extraction with acetonitrile under stirring, 24 hrs, rt;

b:HPLC quantitation of released 11.38 or 11.39.

a:10 washings under stirring with MeOH-AcOH-water 7-1-2, 2 hrs each;

b:incubation with 11.38 or 11.39 solutions (500 M);

c:HPLC quantitation of templates in solution and quantitation of bound 11.38 or 11.39.

Figure 11.26 Double-screening procedure for the MIP discrete libraries L18 and L19.

determination of the template left in the supernatant produced, by difference, the amount of adsorbed template.

The screening results for both procedures were coherent and showed some interesting trends. Ametryn was better adsorbed by L18 individuals containing larger quantities of 11.37, whereas atrazine was better absorbed by 11.36-rich L19 individuals. Even more importantly, a high preference for ametryn versus atrazine was observed for L18, showing that good selectivity is possible even in the presence of extremely similar template structures (see reference 91 for additional details). The semiautomated nature of the library synthesis and screening significantly helped the acquisition and utilization of the large amount of data generated.

The use of higher throughput, combinatorial synthetic/screening processes was extremely useful in observing these trends, which could eventually be used to further refine analogous MIPs. Several other reports have presented small MIP libraries (111) or reported their use in combinatorial technologies as artificial targets to select positives from combinatorial libraries (112–114). Reports on parallel copolymer libraries with varying amounts of functional monomers should become more frequent in the near future.

11.3.7 Sensor Libraries and Technologies

The use of chemical sensors to detect small quantities of a specific analyte, mostly for gas-phase sensing but also for solution substances, has gained importance in the last years in many disciplines (115, 116). Few of these sensors, though, have multianalyte specificity together with a high sensitivity, and research is ongoing to improve the characteristics of the materials that compose the sensors. A very active field is the so-called electronic nose sensor (117, 118), where an artificial sensor system allows both the identification and the quantification of complex vapor mixtures, thus mimicking the sense of smell. Complex computer algorithms then allow the pattern detected by the sensor to be recorded and the vapor components to be identified,

REFERENCES 615

TABLE 11.4 Fluorescence Spectra of L20: Main Featuresa

aN = negative, P = positive, B = biphasic fluorescence. bPercent of MMA in PS802.

spectrum, and thus an optical screening method was adopted to detect the response for L20 to various gas phases.

An array of two copies of each library individual (eight sensing regions) was prepared and exposed to four solvent vapors, measuring the fluorescent response of the sensor array for each of them. A 535-nm light source was used to illuminate the array, and emission spectra were monitored at 629 nm with a CCD camera using 1-s vapor pulses and 5-s recording periods. Forty different images were collected in the 4 s following the vapor pulse. A schematic representation of the sensor is reported in Fig. 11.28, highlighting the presence of the eight sensing regions on the same sensor. The four library components showed high sensitivity and reproducibility of results, but most importantly, the four compositions gave different temporal responses, sometimes varying from positive to negative or even biphasic fluorescence changes in response to the same vapor stimulus (see Table 11.4).

The creation of many effective combinations of artificial nose sensors with only a few functional monomers used in different relative amounts was proven here. The application of combinatorial technologies to the discovery of novel materials for more recent, miniaturized electronic nose systems based on small polymer beads (120), and to equally intriguing electronic tonguelike microsensors in solution to mimick the sense of taste for solution mixtures (121), should be highly beneficial and thus is to be expected in the near future.

The same prediction can easily be formulated for combinatorial polymerization of functional monomers to develop novel materials or to speed the optimization of the properties of existing composites. This is probably, together with materials science, the field where the potential of combinatorial technologies has only barely been perceived and thus is also a discipline for which major outcomes have to be expected in the near future.

REFERENCES

1.Xiang, X.-D., Mat. Sci. Eng. B56, 246–250 (1998).

2.Weinberg, W. H., Jandeleit, B., Self, K. and Turner, H.,Curr. Opin. Solid State Mater. Sci. 3, 104–110 (1998).

616MATERIALS AND POLYMERIC COMBINATORIAL LIBRARIES

3.Xiang, X.-D., Chem. Ind., 800–802 (1998).

4.Jandeleit, B., Turner, H. W., Uno, T., Van Beek, J. A. M. and Weinberg, W. H.,CATTECH2, 101–123 (1998).

5.Schlogl, R., Angew. Chem. Int. Ed. 37, 2333–2336 (1998).

6.McFarland, E. W. and Weinberg, W. H., Trends Biotechnol. 17, 107–115 (1999).

7.Bein, T., Angew. Chem. Int. Ed. 38, 323–326 (1999).

8.Maier, W. F., Angew. Chem. Int. Ed. 38, 1216–1218 (1999).

9.Newsam, J. M. and Schuth, F., Biotech. Bioeng. 61, 203–216 (1999).

10.Xiang, X.-D., Biotech. Bioeng. 61, 227–241 (1999).

11.Xiang, X.-D., Annul Rev. Mater. Sci. 29, 149–171 (1999).

12.Adachi, G., Textbook in Chemistry: Fundamentals of Solid State Chemistry and Inorganic Materials. Maruzen, Tokyo, Japan, 1995.

13.Poeppelmeier, K. R., Chem. Mater. 10, 2577–2578 (1998).

14.Janek, J. and Ruck, M., Nachr. Chem., Tech. Lab. 47, 143–153 (1999).

15.Solid-State Chemistry of Inorganic Materials II , S. M. Kauzlarich, E. M. McCarron, III,

A.W. Sleight and H.-C. Zur Loye (Eds.). Mater. Res. Soc., Warrendale, PA, 1999.

16.Campbell, D. S., Thin Solid Films 32, 3–10 (1976).

17.Dini, J. W., Mater. Manuf. Processes 12, 437–472 (1997).

18.Pawlowski, L., Galvano-Orgrano 66, 532–537 (1997).

19.Hanak, J. J., J. Mater. Sci. 5, 964–971 (1970).

20.DaSilva, E. M. and Terhune, C. E., IBM Tech. Disclosure Bull. 22, 2922 (1979).

21.Fodor, S. P. A., Read, J. L., Pirrung, M. C., Stryer, L. Lu, A. T. and Solas, D.,Science 251, 767–773 (1991).

22.Xiang, X.-D., Sun, X., Briceno, G., Lou, Y., Wang, K.-A., Chang, H., Wallace Freedman,

W.G., Chen, S.-W. and Schultz, P. G., Science 268, 1738–1740 (1995).

23.Kay, E., Tech. Metal Res. 1, 1269–1309 (1968).

24.Rohde, S. L. and Muenz, W., Adv. Surf. Coat., 92–126 (1991).

25.Raven, M. S., J. Mater. Sci.: Mater. Electron. 5, 129–146 (1994).

26.Powell, C. F., Vapor Deposition, 221–248 (1966).

27.Handbook of Physical Vapor Deposition (PVD) Processing: Film Formation, Adhesion, Surface Preparation and Contamination Control , D. M. Mattox (Ed.). Noyes, Westwood, NJ, 1998.

28.Oettel, H., Freiberg. Forschungsh. B B287, 17–33 (1998).

29.Conway, B. E., Prog. Surf. Sci. 16, 1–137 (1984).

30.Electrochemical Phase Formation and Growth: An Introduction to the Initial Stages of Metal Deposition. E. Budevski, G. Staikov, W. J. Lorenz (Eds.) VCH, 1996, Weinheim, Germany.

31.Oskam, G., Long, J. G., Natarajan, A. and Searson, P. C., J. Phys. D: Appl. Phys. 31, 1927–1949 (1998).

32.Egermeier, J. and Hill, R. J., Proc. Annul Tech. Conf.—30th Soc. Vac. Coaters, 329–337 (1987).

33.Ray, A. K., Trans. Met. Finish. Assoc. India 4, 49–55 (1995).

REFERENCES 617

34.Dieleman, J., Van de Riet, E. and Kools, J. C. S.,Jpn. J. Appl. Phys., Part 1 31, 1964–1971 (1992).

35.Hanabusa, M., Proc. Int. Conf: Lasers, 55–62 (1994).

36.Stuke, M., Vide: Sci., Tech. Appl. 54, 484–515 (1998).

37.van Dover, R. B., Schneemeyer, L. F. and Fleming, R. M., Nature 392, 162–164 (1998).

38.Danielson, E., Golden, J. H., McFarland, E. W., Reaves, C. M., Weinberg, W. H. and Wu,

X.D., Nature 389, 944–948 (1997).

39.Danielson, E., Devenney, M., Giaquinta, D. M., Golden, J. H., Haushalter, R. C., McFarland, E. W., Poojary, D. M., Reaves, C. M., Weinberg, W. H. and Wu, X. D.,Science 279, 837–839 (1998).

40.Danielson, E., Devenney, M., Giaquinta, D. M., Golden, J. H., Haushalter, R. C., McFfarland, E. W., Poojary, D. M., Reaves, C. M., Weinberg, W. H. and Wu, X. D., J. Mol. Struc. 470, 229–235 (1998).

41.Briceno, G., Chang, H., Sun, X., Schultz, P. G. and Xiang, X.-D., Science 270, 273–275 (1995).

42.Takeuchi, I., Chang, H., Gao, C., Schultz, P. G., Xiang, X.-D., Sharma, R. P., Downes, M.

J.and Venkatesan, T., Appl. Phys. Lett. 73, 894–896 (1998).

43.Godovsky, D., Inganas, O., Brabec, C. J., Sariciftci, N. S., Hummelen, J. C., Janssen, R.

A.I., Prato, M., Maggini, M., Segura, J. and Martin, N., AIP Conf: Proc. 486, 483–486 (1999).

44.Hill, C. L. and Damico Gall, R., J. Mol. Catal. A 114, 103–111 (1996).

45.Sun, X.-D., Wang, K. A., Yoo, Y., Wallace-Freedman, W. G., Gao, C., Xiang, X. D. and Schultz, P. G., Adv. Mater. 9, 1046–1049 (1997).

46.Akporiaye, D. E., Dahl, I. M., Karlsson, A. and Wendelbo, R.,Angew. Chem. Int. Ed. 37, 609–611 (1998).

47.Klein, J., Lehmann, C. W., Schmidt, H.-W. and Maier, W. F., Angew. Chem. Int. Ed. 37, 3369–3372 (1998).

48.Choi, K., Gardner, D., Hilbrandt, N. and Bein, T., Angew. Chem. Int. Ed. 38, 2891–2894 (1999).

49.Feijen, E. P. and Martens, P. A., Stud. Surf: Sci. Catal. 84, 3–35 (1994).

50.Corma, A., Chem. Rev. 97, 2373–2420 (1997).

51.Holzwarth, A., Schmidt. H.-W. and Maier, W. F., Angew. Chem. Int. Ed. 37, 2644–2647 (1998).

52.Senkan, S. M. and Ozturk, S., Angew. Chem. Int. Ed. 38, 791–795 (1999).

53.Cong, P., Doolen, R. D., Fan, Q., Giaquinta, D. M., Guan, S., McFarland, E. W., Poojary,

D.M., Self, K., Turner, H. W. and Weinberg, W. H., Angew. Chem. Int. Ed. 38, 484–488 (1999).

54.Klein, S., Thorimbert, S. and Maier, W. F., J. Catal. 163, 476–488 (1996).

55.Storck, S., Maier, W. F., Salvado, I. M. M., Ferreira, J. M. F., Guhl, D., Souverijns, W. and Martens, J. A., J. Catal. 172, 414–426 (1997).

56.Georgiades, G., Self, V. A. and Sermon, P. A.,Angew. Chem. Int. Ed. Engl. 26, 1050–1052 (1987).

57.Taylor, S. J. and Morken, J. P., Science 280, 267–270 (1998).

618MATERIALS AND POLYMERIC COMBINATORIAL LIBRARIES

58.Moates, F. C., Somani, M., Annamalai, J., Richardson, J. T., Luss, D. and Willson, R. C.,

Ind. Eng. Chem. Res. 35, 4801–4803 (1996).

59.Srinivasan, R., Hsing, I-M., Berger, P. E., Jensen, K. F., Firebaugh, S. L., Schmidt, M. A., Harold, M. P., Lerou, J. J. and Ryley, J. F., AlChE J. 43, 3059–3069 (1997).

60.Senkan, S. M., Nature 394, 350–353 (1998).

61.Weinberg, W. H., McFarland, E. W., Cong, P. and Guan, S.,WO Patent 9815969 A2 (1998).

62.Cong, P., Dehestani, A., Doolen, R., Giaquinta, D. M., Guan, S., Markov, V., Poojary, D., Self, K., Turner, H. and Weinberg, W. H., Proc. Natl. Acad. Sci. USA 96, 11077–11080 (1999).

63.Senkan, S., Krantz, K., Ozturk, S., Zengin, V. and Onal, I., Angew. Chem. Int. Ed. 38, 2794–2799 (1999).

64.Orschel, M., Klein, J., Schmidt, H.-W. and Maier, W. F., Angew. Chem. Int. Ed. 38, 2791–2794 (1999).

65.Hoffmann, C., Wolf, A. and Schuth, F., Angew. Chem. Int. Ed. 38, 2800–2803 (1999).

66.Reddington, E., Sapienza, A., Gurau, B., Viswanathan, R., Sarangapani, S., Smotkin, E.

S.and Mallouk, T. E., Science 280, 1735–1737 (1998).

67.Watanabe, M., Uchida, M. and Motoo, S., J. Electroanal. Chem. Interfacial Electrochem.

229, 395–406 (1987).

68.Ley, K. L., Liu, R., Pu, C., Fan, Q., Leyarovska, N., Segre, C. and Smotkin, E. S., J. Electrochem. Soc. 144, 1543–1548 (1997).

69.Wang, J., Yoo, Y., Gao, C., Takeuchi, I., Sun, X., Chang, H., Xiang, X. -D. and Schultz, P G., Science 279, 1712–1714 (1998).

70.Sun, X.-D., Gao, C., Wang, J. and Xiang, X.-D., Appl. Phys. Lett. 70, 3353–3355 (1997).

71.Sun, X.-D. and Xiang, X.-D., Appl. Phys. Lett. 72, 525–527 (1998).

72.Isaacs, E. D., Marcus, M., Aeppli, G., Xiang, X.-D., Sun, X.-D., Schultz, P., Kao, H.-K., Cargill, G. S. III and Haushalter, R., Appl. Phys. Lett. 73, 1820–1822 (1998).

73.Wu, J. L., Devenney, M., Danielson, E., Poojary, D. and Weinberg, W. H.,Mat. Res. Soc. Symp. Proc. 560, 65–70 (1999).

74.Chen, C.-M., Pan, H. C., Zhu, D. Z., Hu, J. and Li, M. Q., Nucl. Instr. Meth. Phys. Res. B 159, 81–88 (1999).

75.Sun, T. X., Biotechnol. Bioeng. 61, 193–201 (1999).

76.Chang, H., Gao, C., Takeuchi, I., Yoo, Y., Wang, J., Schultz, P. G., Xiang, X.-D., Sharma,

R.P., Downes, M. and Venkatesan, T., Appl. Phys. Lett. 72, 2185–2187 (1998).

77.Wei, T., Xiang, X.-D., Wallace-Freedman. W. G. and Schultz, P. G., Appl. Phys. Lett. 68, 3506–3508 (1996).

78.van Dover, R. B., Schneemeyer, L. F., Fleming, R. M. and Huggins, H. A., Biotechnol. Bioeng. 61, 217–225 (1999).

79.Park, J.-H., Parise, J. B., Woodward, P. M., Lubomirsky, I. and Stafsudd, O.,J. Mater. Res. 14, 3192–3195 (1999).

80.Klaerner, G., Safir, A. L., Chang, H.-T., Petro, M. and Nielsen, R. B., Polym. Prepr. 40, 469 (1999).

81.Hawker, C. J., Benoil, D., Rivera, F. Jr., Chaplinski, V., Nilsen, A. and Braslau, R.,Polym. Mater. Sci. Eng. 80, 90–91 (1999).

REFERENCES 619

82.Nielsen, R. B., Safir, A. L., Petro, M., Lee, T. S. and Huefner, P., Polym. Mater. Sci. Eng. 80, 92 (1999).

83.Petro, M., Safr, A. L. and Nielsen, R. B., Polym. Mater. Sci. Eng. 80, 702 (1999).

84.Frechet, J. M. J., Polym. Mater. Sci. Eng. 80, 494 (1999).

85.Schmitz, C., Posch, P., Thelakkat, M. and Schmidt, H.-W., Phys. Chem. Chem. Phys. 1, 1777–1781 (1999).

86.Wurthner, F., Sens, R., Etzbach, K.-H. and Seybold, G., Angew. Chem. Int. Ed. 38, 1649–1652 (1999).

87.Wang, J. and Gonsalves, K. E., J. Comb. Chem. 1, 216–222 (1999).

88.Reynolds, C. H., J. Comb. Chem. 1, 297–306 (1999).

89.Newkome, G. R., Pure Appl. Chem. 70, 2337–2343 (1999).

90.Gravert, D. J. and Janda, K. D., Chem. Rev. 97, 489–509 (1997).

91.Gravert, D. J., Datta, A., Wentworth, P., Jr. and Janda, K. D., J. Am. Chem. Soc. 120, 9481–9495 (1998).

92.Li, I. Q., Howell, B. A., Dineen, M. T., Kastl, P. E., Lyons, J. W., Meunier, D. M., Smith, P. B. and Priddy, D. B., Macromolecules 30, 5195–5199 (1997).

93.Newkome, G. R., Weis, C. D., Moorefield, C. N., Baker, G. R., Childs, B. J. and Epperson, J., Angew. Chem. Int. Ed. 37, 307–310 (1998).

94.Newkome, G. R., Weis, C. D., Moorefield, C. N. and Fronczek, F. R., Tetrahedron Lett. 38, 7053–7056 (1997).

95.Newkome, G. R., Weis, C. D. and Childs, B. J., Des. Monom. Polym. 1, 3–14 (1998).

96.Worner, C. and Mulhaupt, R., Angew. Chem., Int. Ed. Engl. 32, 1306–1308 (1993).

97.Menger, F. M., West, C. A. and Ding, J., Chem. Commun., 633–634 (1997).

98.Talma, A. G., Jouin, P., De Vries, J. G., Troostwijk, C. B., Werumeus Buning, G. H., Waininge, J. K., Visscher, J. and Kellogg, R. M., J. Am. Chem. Soc. 107, 3981–3997 (1985).

99.Engbersen, J. F. J., Koudijs, A. and Van der Plas, H. C., J. Org. Chem. 55, 3647–3654 (1990).

100.Menger, F. M., Ding, J. and Barragan, V., J. Org. Chem. 63, 7578–7579 (1998).

101.Choi, S.-K., Mammen, M. and Whitesides, G. M., J. Am. Chem. Soc. 119, 4103–4111 (1997).

102.Menger, F. M., Eliseev, A. V. and Migulin, V. A., J. Org. Chem. 60, 6666–6667 (1995).

103.Miller, P. D. and Ford, W. T., Chem. Commun., 1151–1152 (1998).

104.Brocchini, S., James, K., Tangpasuthadol, V. and Kohn, J., J. Am. Chem. Soc. 119, 4553–4554 (1997).

105.Brocchini, S., James, K., Tangpasuthadol, V. and Kohn, J., J. Biomed. Mater. Res. 42, 66–75 (1998).

106.Hooper, K. A. and Kohn, J., J. Bioact. Compat. Polym. 10, 327–340 (1995).

107.Fiordeliso, J., Bron. S. and Kohn, J., J. Biomater. Sci. Polym. Ed. 5, 497–510 (1994).

108.Wulff, G., Angew. Chem. Int. Ed. Engl. 34, 1812–1832 (1995).

109.Ensing, K. and de Boer, T., Trends Anal. Sci. 18, 138–145 (1999).

110.Takeuchi, T., Fukuma, D. and Matsui, J., Anal. Chem. 71, 285–290 (1999).

620MATERIALS AND POLYMERIC COMBINATORIAL LIBRARIES

111.Sabourin, L., Ansell, R. J., Mosbach, K. and Nicholls, I. A.,Anal. Commun. 35, 285–287 (1998).

112.Berglund, J., Lindbladh, C., Mosbach, K. and Nicholls, I. A., Anal. Commun. 35, 37 (1998).

113.Ramstrom, O., Ye, L. and Mosbach, K., Anal. Commun. 35, 9–11 (1998).

114.Ramstroem, O., Ye. L., Krook, M. and Mosbach, K., Chromatographia 47, 465–469 (1998).

115.Ricco, A. J. and Crooks, R. M., Acc. Chem. Res. 31, 200 (1998).

116.Crooks, R. J. and Ricco, A. J., Acc. Chem. Res. 31, 219–227 (1998).

117.Walt, D. R., Acc. Chem. Res. 31, 267–278 (1998).

118.Dickinson, T. A., White, J., Kauer, J. S. and Walt. D. R., Trends Biotechnol. 16, 250–258 (1998).

119.Dickinson, T. A. and Walt, D. R., Anal. Chem. 69, 3413–3418 (1997).

120.Dickinson, T. A., Michael, K. L., Kauer, J. S. and Walt, D. R.,Anal. Chem. 71, 2192–2198 (1999).

121.Lavigne, J. J., Metzger, A., Niikura, K., Cabell, L. A., Savoy, S. M., Yoo, J. S.-J., McDevitt, J. T., Neikirk, D. P., Shear, J. B. and Anslyn, E. V., Proc. SPIE-Int. Soc. Opt. Eng. 3602, 17–26 (1999).