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Polymer conjugates of camptothecin (CPT) have been pursued as a solution to the difficulties present in treating cancers with CPT and its derivatives. Covalent attachment of CPT to a polymer can improve solubility, increase blood circulation time, enhance tumor uptake, and significantly improve efficacy of the drug. In this report, we describe a novel polymer conjugate of CPT using a core-functionalized, symmetrically PEGylated poly(l-lysine) (PLL) dendrimer. The PEGylated dendrimer consisted of a lysine dendrimer functionalized with aspartic acid, which was used as an attachment site for poly(ethylene glycol) (PEG) and CPT. The final conjugate had a molecular weight of 40 kDa and was loaded with 4-6 wt % CPT. Polymer-bound CPT was shown to have a long blood circulation half-life of 30.9 +/- 8.8 h and a tumor uptake of 4.2 +/- 2.3% of the injected dose/g of tissue, compared to free CPT in which less than 1% was retained in the blood after 30 min and had a tumor accumulation of 0.29 +/- 0.04% of the injected dose/g of tissue. The PEGylated PLL-CPT showed superior efficacy in murine (C26) and human colon carcinoma (HT-29) tumor models when compared with no treatment or treatment with irinotecan. In the C26 tumor model, treatment resulted in significantly prolonged survival (P0.05) for all mice treated with a single injection of PEGylated PLL-CPT. In the HT-29 tumor model, all mice treated with multiple injections of a low dose survived to the end of the study, with three mice of eight surviving tumor-free.

We describe the rational design of oligothiophene semiconductors to facilitate solution-based fabrication of environmentally stable organic field-effect transistors (OFETs). Ultrathin films of α,ω-distyryl quaterthiophene (DS4T), pentathiophene (DS5T), and sexithiophene (DS6T) were prepared via solution processing to probe the effect of styryl end groups, oligomer length, and thin film structure on air stability. These films were prepared via solution deposition and thermal annealing of precursors featuring thermally labile ester solubilizing groups. A detailed study of the thin film structure was performed using atomic force microscopy (AFM), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, and grazing incidence X-ray diffraction (GIXD). Functional OFETs were obtained for DS5T and DS6T and have, respectively, hole mobilities of 0.051 and 0.043 cm2/(V s) and on/off ratios of 1 × 105 to 1 × 106, whereas DS4T OFETs failed to function because of poor film continuity. The effect of both short-...

Bipolar transport polymers have been developed as host materials for electroluminescent devices by incorporating both electron-transporting and hole-transporting functionalities into copolymers. Two different copolymers having the same molecular weight (Mn ∼ 30 kg/mol) and the same fraction of electron-transporting monomers (fOXA = 0.50) have been synthesized in the form of random and diblock copolymers, respectively. The effect of molecular structure and film morphology of these bipolar polymers on device performance has been studied. For the diblock copolymers, pronounced phase segregation forming different nanomorphologies has been observed by modern microscopic techniques, which is not observed for the random counterparts under the same thin film preparation conditions. The results of single-layer polymer light emitting diodes (PLEDs) show that the nanophase separation morphology of diblock copolymers has a significant effect on device performance: lowering charge transport and facilitating the hole−...

Hydrogen adsorption using a series of nanoporous synthetic polymers has been studied. Promising results were obtained during the screening of commercially available porous polymer beads; of the polymers considered, hypercrosslinked Hypersol-Macronet MN200 resin exhibited the highest adsorption capacity for hydrogen. This initial success triggered the development of our own high surface area hypercrosslinked materials. Subjecting gel-type and macroporous vinylbenzyl chloride-based precursors swollen in dichloroethane to a Friedel−Crafts reaction catalyzed by iron trichloride afforded beads with surface areas of 1 930 and 1 300 m2/g, respectively, as calculated using the BET equation. The former polymer reversibly stores up to 1.5 wt % H2 at a pressure of 0.12 MPa and a temperature of 77.3 K. The initial heat of adsorption of hydrogen molecules onto this polymer is 6.6 kJ/mol.

Symmetrical α,ω-substituted quarter-(T4), penta-(T5), sexi-(T6), and heptathiophene (T7) oligomers containing thermally removable aliphatic ester solubilizing groups were synthesized, and their UV−vis and thermal characteristics were compared. Spun-cast thin films of each oligomer were examined with atomic force microscopy and near-edge X-ray absorption fine structure spectroscopy to evaluate the ability of the material to self-assemble from a solution-based process while maintaining complete surface coverage. Films of the T5−T7 oligomers self-assemble into crystalline terraces after thermal annealing with higher temperatures required to affect this transformation as the size of the oligomers increases. A symmetrical α,ω-substituted sexithiophene (T6-acid) that reveals carboxylic acids after thermolysis was also prepared to evaluate the effect of the presence of hydrogen-bonding moieties. The charge transport properties for these materials evaluated in top-contact thin film transistor devices were found t...

The role of architecture and nanoenvironment in the catalytic properties of dendritic polymers containing 4-(dialkylamino)pyridines was investigated in the context of acylation reactions employing sterically demanding tertiary alcohols as substrates. Frechet-type benzyl ether and aliphatic ester dendrimers were prepared in a convergent manner from a common trivalent core containing three DMAP groups while a linear polymer was dendronized with aliphatic esters using a divergent growth scheme. Catalysis experiments clearly indicate that nanoenvironment plays the dominant role in determining the activity of the polymer catalysts, with the polyester platform being superior to the benzyl ether. Polymer architecture played little or no role in affecting catalysis. With respect to molecular transport and catalysis, this represents the first comparative study of the effect of architecture and nanoenvironment using structurally similar dendritic materials.

[structure: see text] A series of bridged oligothiophenes have been synthesized. Their novel molecular architecture, comprising two oligothiophenes linked together by a bridge at one alpha-extremity and one binding group at the other alpha-extremity, is expected to improve their utility as electroactive surfactants for semiconducting nanoparticles or organic electronics.

High molecular weight polymers (> 20 000 Da) have been widely used as soluble drug carriers to improve drug targeting and therapeutic efficacy. Dendritic polymers are exceptional candidates for the preparation of near monodisperse drug carriers due to their well-defined structure, multivalency, and flexibility for tailored functionalization. We evaluated various dendritic architectures composed of a polyester dendritic scaffold based on the monomer unit 2,2-bis(hydroxymethyl)propanoic acid for their suitability as drug carriers both in vitro and in vivo. These systems are both water soluble and nontoxic. In addition, the potent anticancer drug, doxorubicin, was covalently bound via a hydrazone linkage to a high molecular weight 3-arm poly(ethylene oxide)-dendrimer hybrid. Drug release was a function of pH, and the release rate was more rapid at pH < 6. The cytotoxicity of the DOX-polymer conjugate measured on multiple cancer lines in vitro was reduced but not eliminated, indicating that some active doxorubicin was released from the drug polymer conjugate under physiological conditions. Furthermore, biodistribution experiments show little accumulation of the DOX-polymer conjugate in vital organs, and the serum half-life of doxorubicin attached to an appropriate high molecular weight polymer has been significantly increased when compared to the free drug. Thus, this new macromolecular system exhibits promising characteristics for the development of new polymeric drug carriers.

Capillaries with inner diameters of 550 microm have successfully been packed with 1.5-microm octadecyl silica particles using frits made of macroporous polymers by the UV photopolymerization of a solution of glycidyl methacrylate and trimethylolpropane trimethacrylate. This type of frit is found superior to one made of low-melting point poly(styrene-co-divinylbenzene) beads. Bubble formation is not observed to occur within these capillary columns under our experimental conditions. Separations can be achieved with sample injection volumes as high as 1 microL. To demonstrate its semipreparative use, a mixture of 500 nL of taxol (20 mM) and its precursor, baccatin III (30 mM), is separated using such a column with a Tris buffer.

The synthesis of functional aromatic bis(sulfonyl chlorides) containing an acetophenone and two sulfonyl chloride groups, i.e., 3,5-bis[4-(chlorosulfonyl)phenyl]-1-acetophenone (16), 3,5-bis(chlorosulfonyl)-1-acetophenone (17), and 3,5-bis(4-(chlorosulfonyl)phenyloxy)-1-acetophenone (18) via a sequence of reactions, involving in the last step the quantitative oxidative chlorination of S-(aryl)- N,N'-diethylthiocarbamate, alkyl- or benzyl thiophenyl groups as masked nonreactive precursors to sulfonyl chlorides is described. A related sequence of reactions was used for the synthesis of the aromatic trisulfonyl chloride 1,1,1-tris(4-chlorosulfonylphenyl)ethane (24). 4-(Chlorosulfonyl)phenoxyacetic acid, 2,2-bis[[[4-(chlorosulfonyl)phenoxyacetyl]oxy]methyl]-1,3-propanediyl ester (27), 5,11,17,23-tetrakis(chlorosulfonyl)-25,26,27,28-tetrakis(ethoxycarbonylmethoxy)calix[4]arene (38), 5,11,17,23,29,35-hexakis(chlorosulfonyl)-37,38,39,40,41,42-hexakis(ethoxycarbonylmethoxy)calix[6]arene (39), 5,11,17,23,29,35,41,47-octakis(chlorosulfonyl)-49,50,51,52,53,54,55,56-octakis(ethoxycarbonylmethoxy)calix[8]arene (40), 5,11,17,23-tetrakis(tert-butyl)-25,26,27,28-tetrakis(chlorosulfonyl phenoxyacetoxy)calix[4]arene (44), 5,11,17,23,29,35-hexakis(tert-butyl)-37,38,39,40,41,42-hexakis(chlorosulfonylphenoxyacetoxy)calix[6]arene (45), and 5,11,17,23,29,35,41,47-octakis(tert-butyl)-49,40,51,52,53,54,55,56-octakis(chlorosulfonylphenoxyacetoxy)calix[8]arene (46) were synthesized by two different multistep reaction procedures, the last step of both methods consisting of the chlorosulfonation of compounds containing suitable activated aromatic positions. 2,4,6-Tris(chlorosulfonyl)aniline (47) was obtained by the chlorosulfonation of aniline. The conformation of two series of multisulfonyl chlorides i.e., 38, 39, 40 and 44, 45, 46, was investigated by (1)H NMR spectroscopy. The masked nonreactive precursor states of the functional aromatic multisulfonyl chlorides and the aromatic multisulfonyl chlorides reported here represent the main starting building blocks required in a new synthetic strategy elaborated for the preparation of dendritic and other complex organic molecules.

During the last years, efforts have been made to encapsulate porphyrins1 within dendrimers to tune their photophysical,2 electrochemical,3 and chemical4 properties. Work carried out in several laboratories has demonstrated the profound ability of a dendritic shell to isolate the porphyrin core moiety facilitating the design of hemeprotein mimics. Unfortunately, dendrimer synthesis is usually time-consuming, and a more rapid route to encapsulated porphyrins that preserves the architectural and functional control afforded by a dendritic shell is desired. Recent advances in the area of “living” ring opening polymerization (ROP) of -caprolactone5 have enabled the accurate construction of star-shaped polymers.6 We sought to take advantage of this methodology coupled with the space filling branching approach of dendrimer synthesis to achieve site isolation of porphyrins. Our approach is based on a highly branched porphyrin core that acts as a multisite initiator for the ROP of -caprolactone. Versatile modification of the core and the end-group functionalities renders the synthesis flexible, allowing one to tailor-design a variety of functional star polymers. Such materials may be of general applicability in the design of oxidation catalysts7 as well as energyharvesting8 and optoelectronic devices.9 Starting from tetrakis(4-hydroxyphenyl)porphyrin 1a and tetrakis(3,5-dihydroxyphenyl)porphyrin 1b, respectively, the initiators 2a,b were prepared via esterification employing acetonide-protected 2,2-bis(hydroxymethyl)-propionic acid10 followed by deprotection of the diol functionalities under acidic conditions (Scheme 1). By using the methodology developed by Trollsas and Hedrick,6a-c we obtained star polymers 3a,b possessing either 8 or 16 arms by bulk polymerization of -caprolactone with initiators 2a,b and tin(II) 2-ethylhexanoate (Sn(Oct)2) as the catalyst. By adjusting the monomer-to-initiator ratio, we could prepare polymers with varying chain lengths and low polydispersities in almost quantitative yields (Table 1). To tune the properties of these materials, we accomplished further modification of the dendritic stars by metalation of the core moiety as well as by derivatization of the hydroxyl-functional chain ends (Scheme 2). Insertion of zinc(II) into the free base porphyrin gave 4b, which is easily identified by its characteristic electronic absorption spectrum in the Q-band region11 (Figure 1a). Introduction of the dye coumarin at each of the 16 hydroxyl chain ends of 3b was easily accomplished by esterification with coumarin-3-carboxylic acid chloride affording 5b. The additivity of the individual coumarin chromophore units contributes to the large absorption in the UV region of the spectrum (Figure 1a). The proton NMR spectra of 3b and 5b (Figure 1b) reveal a significant downfield shift of the signal associated with the end groups of 3b (CH2OH) by conversion to the coumarin esters in 5b. Due to the energetic match between the emission of the coumarin donors and the absorption of the porphyrin acceptor, compounds such as 5b offer the opportunity of efficient light harvesting and resonance energy transfer.12 Further studies of these processes are currently underway. A significant advantage of the high yield processes used is that the only purification required after polymerization, metalation, (1) For an introduction to porphyrin chemistry, see: Milgrom, L. R. The Colours of Life; Oxford University Press: Oxford, U.K., 1997, and references therein. (2) (a) Jin, R.-H.; Aida, T.; Inoue S. J. Chem. Soc., Chem. Commun. 1993, 1260. (b) Tomoyose, Y.; Jiang, D.-L.; Jin, R.-H.; Aida, T.; Yamashita, T.; Horie, K.; Yashima, E.; Okamoto, Y. Macromolecules 1996, 29, 5236. (c) Sadamoto, R.; Tomioka, N.; Aida, T. J. Am. Chem. Soc. 1996, 118, 3978. (d) Pollak, K. W.; Leon, J. W.; Frechet, J. M. J.; Maskus, M.; Abruna, H. D. Chem. Mater. 1998, 10, 30. (e) Pollak, K. W.; Sanford, E. M.; Frechet, J. M. J. J. Mater. Chem. 1998, 8, 519. (f) Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 1998, 120, 10895. (3) (a) Dandliker, P. J.; Diederich, F.; Gross, M.; Knobler, C. B.; Louati, A.; Sanford, E. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 1739. (b) Dandliker, P. J.; Diederich, F.; Gisselbrecht, J.-P.; Louati, A.; Gross, M. Angew. Chem., Int. Ed. Engl. 1995, 34, 2725. (c) Dandliker, P. J.; Diederich, F.; Zingg, A.; Gisselbrecht, J.-P.; Gross, M.; Louati, A.; Sanford, E. M. HelV. Chim. Acta 1997, 80, 1773. (4) (a) Jiang, D.-L.; Aida, T. Chem. Commun. 1996, 1523. (b) Collman, J. P.; Fu, L.; Zingg, A.; Diederich, F. Chem. Commun. 1997, 193. (c) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708. (d) Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262. (5) For a recent review, consult Lofgren, A.; Albertsson, A.-C.; Dubois, P.; Jerome, R. J. Macromol. Sci., ReV. Macromol. Chem. Phys. 1995, C35, 379. (6) (a) Trollsas, M.; Hedrick, J. L.; Mecerreyes, D.; Dubois, P.; Jerome, R.; Ihre, H.; Hult, A. Macromolecules 1997, 30, 8508. (b) Trollsas, M.; Hedrick, J. L.; Mecerreyes, D.; Dubois, P.; Jerome, R.; Ihre, H.; Hult, A. Macromolecules 1998, 31, 2756. (c) Trollsas, M.; Hedrick, J. L. J. Am. Chem. Soc. 1998, 120, 4644, and references therein. (7) Detailed review are given in (a) Sheldon, R. A., Ed. Metalloporphyrins in Catalytic Oxidations; Marcel Dekker: New York, 1994. (b) Montanari, F., Casella, L., Eds. Metalloporphyrin Catalyzed Oxidations; Kluwer: London, 1995. (8) For a recent discussion, see Freemantle, M. Chem. Eng. News 1998, (10/26), 37. (9) An enhancement of the luminescence properties of lanthanide ions using the concept of site isolation has recently been reported: Kawa, M.; Frechet, J. M. J. Chem. Mater. 1998, 10, 286. (10) Ihre, H.; Hult, A.; Frechet, J. M. J.; Gitsov, I. Macromolecules 1998, 31, 4061. (11) (a) Buchler, J. W. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978; Vol. I, Part A, p 390. (b) Smith, K. M. In Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevier: New York, 1976; p 3 and appendix p 871. (12) For a related study, see Gilat, S. L.; Adronov, A.; Frechet, J. M. J. Angew. Chem., Int. Ed. Engl. 1999, 38, 1422. Scheme 1

Reaction d'un magnesium insoluble (complexe Mg anthracene)THF avec un polymere halogene solide