Cooperative Formation of Inorganic-Organic interfaces in the synthesis of silicate mesostructures

Cooperative Formation of Inorganic-Organic interfaces in the synthesis of silicate...

(Parte 2 de 2)

In addition, we investigated the influence of the ionic strength on the surfactantsilicate assembly process by performing the

synthesis in a reaction solution also containing 1 M NaCI. The presence of the salt decreased the regularity of the material, as reflected by a reduction in the number of peaks in the x-ray pattern (from four to two). This effect, expected only at high ionic strengths, is attributed to perturbation of the double layer potential. The strong binding constant of silicate species compared to other ions makes this effect negligible at lower ionic strengths and explains why mesostructure syntheses are relatively insensitive to other counterions in the reaction mixture.

The existence of the cubic mesophase described by Beck et al. (2) is strongly supportive of the important role of Gintra + Ginter in the formation of surfactant-silicate mesostructures. Indeed, there is remarkable similarity between the cubic mesophase, which we have recently synthesized and characterized, and the Ia3d phase found in the water-CTABr system (4). A TEM im- age of the cubic mesostructure material (Fig. 6) shows an ordered -2000 A aggregate. The x-ray powder spectrum (Fig. 7) agrees very well with the model Q230 proposed by Mariani et al. (21) for watersurfactant systems. For this structure, it is appealing to conjecture that the midplane of the silicate wall sits on a gyroid periodic minimal surface (2). Such a structure can then be viewed as a single infinite silicate sheet that separates the surfactant species into two equal and disconnected volumes. This so-called bicontinuous phase will be formed when the value of AO set by the reaction conditions is close to the value of the Ia3d phase, namely, when pH and the

CTA/SiO2 ratio are high. It is advantageous for the silicate wall to occupy a periodic minimal surface, because it can maximize the wall thickness for a given CTA/SiO2 volume fraction.

The leading role of Gintra + Ginter in directing mesostructure formation provides a foundation for identifying potential replacement candidates for silicon in the synthesis of mesoporous inorganic frameworks. The principal criteria are that the inorganic component must be capable of forming flexible polyionic species, that extensive polymerization of the inorganic component must be possible, and that charge density matching between the surfactant and inorganic species has to occur.

In other words, when G5,, plays a benign role, Gwall must not dominate Gintra +

Ginter in order that the mesostructure form. In addition to binding efficiently to the surfactant interface, the best inorganic candidates will have a tendency to form glasses easily. Silicates are certainly a prototypic system in view of the ease with which they form oligomeric anions with varying de- grees of polymerization. Other systems, however, may also fulfill these requirements, including transition metals, such as vanadium, or main group elements, such as boron, which can form polyanions and condense. One can also speculate about a reversed system in which an anionic surfactant is used to precipitate a cationic metal oxide precursor, the laurylsulfate-iron oxide system representing one candidate example. Existing experimental data thus far con- firm the trends predicted for the formation of surfactant-silicate mesostructures by the qualitative model outlined above. Cooperative binding provides an explanation for the strong interactions needed to precipitate mesophases from dilute solutions. Preferential polymerization of silicates in the region of the interface together with a double layer control of the wall thickness are responsible for the high regularity of the surfactant-silicate mesostructures. Charge density matching establishes a link between the chemical composition and structure of the silicate wall and the formation of a particular mesostructure. We expect that these perspectives will stimulate and guide experiments aimed at producing and exploiting a better understanding of this exciting class of materials.

1. C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C. Vartuli, J. S. Beck, Nature 359, 710 (1992).

2. J. S. Beck et al., J. Am. Chem. Soc. 114, 10834 (1992). 3. R. G. Laughlin, Surfactant Sci. Ser. 37, 1 (1991).

4. X. Auvray, C. Petipas, R. Anthore, I. Rico, A. Lattes, J. Phys. Chem. 93, 7458 (1989).

5. The general procedure for synthesizing mesostructure materials is as follows: An aqueous solution containing silica and optional tetrameth- ylammonium hydroxide (TMAOH) is stirred into an aqueous solution containing the surfactant and an optional aluminum source. The resulting mixture is kept at temperatures between 298 and 423 K for reaction times between 5 min and 3 days in either closed Teflon bottles or under stirring and refluxing in a glass flask. For silica sources, we used Cab-O-Sil M-5 (Kodak, Rochester, NY), an aqueous solution of sodium silicate (27.5% SiO2, SiO2/Na2O = 3.2 from P0 Corporation, Valley Forge, PA), or tetraethylorthosilicate (TEOS) (Aldrich, Milwaukee, WI). Aluminum sources were boehmite (CATAPAL B from Alumina Vista, Houston, TX) or sodium aluminate (Spectrum Chemical, Gardena, CA). Quarter- nary ammonium alkyls CH2,1 (CH3)3NX, where X = Cl- or Br- and n = 8 to 18, and TMAOH were obtained from Aldrich.

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6. The expression "surfactant-silicate" is used here as a comprehensive term for materials synthesized using a mixture of surfactant and silica species, regardless of the particular structure. 7. The transformation between the lamellar and hexagonal mesophases was observed after freeze-drying, as well as air-drying, the filtered samples.

8. Addition of trimethylbenzene (TMB) to the reaction mixture stabilizes the lamellar mesophase. Experiments have shown that the 31 (±1) A repeat distance for the layered material shown in Figs. 2A and 3 is preserved over a range of TMB concentrations between 0.5 and 3.0 M, whereas at lower TMB concentrations the hexagonal mesostructure is the favored product. Stabiliza- tion of the lamellar mesophase likely occurs because TMB dissolved within the surfactant hydrocarbon assemblies contributes to the hydrophobic chain volume. This increase in surfac- tant chain volume increases the value of AO at which the lamellar-to-hexagonal mesophase transformation occurs, according to a simple geometric model (13). Thus, the mesostructural transformation depicted in Fig. 2 is a conse- quence of hydrothermal removal of TMB from within the surfactant chain assembly, combined with an increase in AO. This conclusion is supported by separate experiments which show that addition of TMB to the aqueous phase inhibits the transformation from a lamellar to a hexagonal mesostructure.

9. R. K. Harris, C. T. G. Knight, W. E. Hull, ACS

Symp. Ser. 194, 79 (1982); C. T. G. Knight, R. G. Kirkpatrick, E. Oldfield, J. Magn. Reson. 78, (1988); A. V. McCormick and A. T. Bell, Catal. Rev. Sci. Eng. 31, 97 (1989).

10. R. K. Iler, The Chemistry of Silica (Wiley, New York, 1979), p. 182.

1. C. J. Brinker, G. W. Scherer, Sol-Gel Science

(Academic Press, New York, 1990), p. 100. 12. K. Hagakawa and J. C. T. Kwac, Surfactant Sci.

Ser. 37,189 (1991). 13. J. Charvolin and J. F. Sadoc, J. Phys. 48, 1559 (1987). J. N. Israelachvili [in Surfactants in Solution, K. L. Mittal and P. Bothorel, Eds. (Plenum, New York, 1987), vol. 4, p. 3] proposed the dimensionless parameter g = V/A0t0 as a means of determining the preferred configuration of a surfactant assembly, where V is the volume of the hydrophobic chain and te is the characteristic chain length. According to this treatment, spherical micelles will form if g < 1/3, cylindrical micelles if 1/3 < g < 1/2, vesicles or bilayers if 1/2 < g < 1, and inverted micelles if g > 1.

14. As discussed in (7), the presence of TMB in the reaction mixture can, but does not always, require a swelling response in surfactant systems. 15. A. Weiss, Clays and Clay Minerals. Proceedings of the National Conference on Clays and Clay Minerals (Earl Ingerso, New York, 1961), vol. 10, p. 191.

16. A. Weiss, Angew. Chem. Int. Ed. EngI. 20, 850 (1981). 17. The hexagonal shape of the mesopores can be determined from the y intercept of a plot of d spacings versus the number of carbon atoms for different chain length surfactants, corrected for the head-group diameter. 18. Calculated from d spacings, volumetric consider- ations (based on a measured void fraction of

0.65), and x-ray diffraction refinements based on the use of cylinder- and hexagonal-prismatic-rodpacking as models. 19. A. Monnier and G. D. Stucky, unpublished work.

20. T. Yanagisawa, T. Shimizu, K. Kuroda, C. Kato,

Bull. Chem. Soc. Jpn. 63, 988 (1990). 21. P. Mariani, V. Luzzati, H. Delacroix, J. Mol. Biol. 204,165 (1988). 2. A periodic minimal surface is the smallest surface separating a volume into two equal parts, given a certain periodic constraint. 23. We thank J. lsraelachvili, J. Zasadzinski (UCSB),

C. Kresge, D. Olson, J. Beck, J. Vartuli, and J. Higgins (Mobil) for helpful discussions. This research was funded by Air Products, du Pont, the

MRL Program of the National Science Foundation under award DMR 9123048, the Office of Naval Research (G.D.S.), the NSF Science and Technol- ogy Center for Quantized Electronic Structures (grant DMR91-20007), the NSF/NYI program, and the Camille and Henry Dreyfus Foundation (B.F.C.) and through fellowships by the FNRS

(A.M.) and the DFG (F.S.).

An Unnatural Biopolymer

Charles Y. Cho, Edmund J. Moran,* Sara R. Cherry,

James C. Stephans, Stephen P. A. Fodor, Cynthia L. Adams, Arathi Sundaram, Jeffrey W. Jacobs, Peter G. Schultzt

A highly efficient method has been developed forthe solid-phase synthesis of an "unnatural biopolymer" consisting of chiral aminocarbonate monomers linked via a carbamate back- bone. Oligocarbamates were synthesized from N-protected p-nitrophenyl carbonate monomers, substituted with a variety of side chains, with greater than 9 percent overall coupling efficiencies per step. A spatially defined library of oligocarbamates was generated by using photochemical methods and screened for binding affinity to a monoclonal antibody. A number of high-affinity ligands were then synthesized and analyzed in solution with respect to their inhibition concentration values, water/octanol partitioning coefficients, and proteolytic stability. These and other unnatural polymers may provide new frameworks for drug development and for testing theories of protein and peptide folding and structure.

Polypeptides have been the focus of considerable attention with respect to their structure and folding, biological function, and therapeutic potential. The development of efficient solid-phase methodology for the synthesis of peptides (1), peptide derivatives (2), and large peptide libraries (3-8) has greatly facilitated these studies. The development of efficient methods for the synthesis of unnatural biopolymers (9- 1 1) composed ofbuilding blocks other than amino acids may provide new frameworks for generating macromolecules with novel properties. For example, polymers with improved pharmacokinetic properties (such as membrane permeability and biological sta- bility) might facilitate drug discovery, and polymers with altered conformational or hydrogen-bonding properties may provide increased insight into biomolecular structure and folding. We report the highly efficient solid-phase synthesis of oligocarbamate polymers from a pool of chiral aminocarbonates and the synthesis and screening of a library of oligocarbamates for their ability to bind a monoclonal antibody (mAb).

The oligocarbamate backbone (Fig. 1), in contrast to that of peptides, consists of a chiral ethylene backbone linked through relatively rigid carbamate groups. The a carbon, like that of peptides, is substituted

C. Y. Cho, E. J. Moran, S. R. Cherry, J. C. Stephans, P. G. Schultz, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720. S. P. A. Fodor, C. L. Adams, A. Sundaram, J. W. Jacobs, Affymax Research Institute, 4001 Miranda Avenue, Palo Alto, CA 94304.

*Present address: Ontogen Corporation, 2325 Camino Vida Roble, Carlsbad, CA 92009.

tTo whom correspondence should be addressed.

with side chains that contain a variety of functional groups. Although the I carbon is unsubstituted in our initial target, additional backbone modifications (and conformational restriction) can be incorporated via alkylation of the IB carbon or the car- bamyl nitrogen. Oligocarbamates were synthesized from a pool of optically active N-protected aminocarbonates (Fig. 2) which, in turn, were derived from the corresponding optically active amino alcohols. The latter are either commercially available or can be prepared in chiral form by reduction of the N-hydroxysuccinimidyl or pentafluorophenyl esters of N-protected amino acids (12). The a-amino group was protected with the use of either nitroveratryl chloroformate (13) (NVOC-CI) (for photochemical deprotection) or fluorenylmethyl-N-hydroxysuccinimidyl carbonate (Fmoc-OSu) (for base-catalyzed deprotec- tion) (14). When necessary, side chains were protected as acid-labile tert-butyl es- ters, ethers, or carbamates. Protected amino alcohols were converted to the corre- sponding N-protected p-nitrophenyl carbonate monomers by reaction with p-nitrophenyl chloroformate in pyridine/CH2C12, generally in >80% yield. The carbonate monomers are stable for months at room temperature.

Solid-phase synthesis of oligocarbamates involves the sequential base-catalyzed or light-dependent deprotection of the a-amino group of the growing polymer chain followed by coupling to the next protected p-nitrophenyl carbonate monomer (Fig. 2). The N-protected "hydroxy-terninal" residue was covalently attached to polystyrene resin containing either N-protected p-alkoxybenzyl amino on February 18, 2010 Downloaded from

(Parte 2 de 2)