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Crowding, which characterizes the interior of all living cells, has been shown to dramatically affect biochemical processes, leading to stabilization of compact morphologies, enhanced macromolecular associations, and altered reaction rates. Due to the crowding-mediated shift in binding equilibria toward association, crowding agents were proposed to act as a metabolic buffer, significantly extending the range of intracellular conditions under which interactions occur. Crowding may, however, impose a liability because, by greatly and generally enhancing macromolecular association, it can lead to irreversible interactions. To better understand the physical determinants and physiological consequences of crowding-mediated buffering, we studied the effects of crowding, or excluded volume, on DNA structures. Results obtained from isothermal titration calorimetry (ITC) and UV melting experiments indicate that crowding-induced effects are marginal under conditions that a priori favor association of DNA strands but become progressively larger when conditions deteriorate. As such, crowding exerts "genuine" buffering activity. Unexpectedly, crowding-mediated effects are found to include enthalpy terms that favorably contribute to association processes. We propose that these enthalpy terms and preferential stabilization derive from a reconfiguration of DNA hydration that occurs in dense DNA-rich phases obtained in crowded environments.

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SynopsisHalomethylation of polysulfone ( P S ) with C8H170CH2X ( X = Cl, Br) in the presence of SnX4 ( X = C1, Br) led to PS-CH2X ( X = C1 or Br or both) (Scheme 1 ) . Under controlled conditions, PS-CH,X could be isolated and retains the good film forming properties of PS itself. Interhalogen exchange reactions occur in the presence of SnX, ( X = C1, Br) under anhydrous conditions (Scheme l ) , or a quaternary ammonium phase transfer catalyst R*R3N+X -, under aqueous conditions (Scheme 2 ) . The exchange reactions with R*R,N+X -, are favored when R = C8-Clo, and with R = C, only if n-octanol is added; otherwise gelation occurs. Exchange in CHC13 is attributed to dehydrohalogenation (and generation of dichlorocarbene) of the solvent in the presence of tetrabutyl ammonium hydroxide. Further chemical modifications of PS-CH2X by reaction with strong nucleophiles, led to hydroxymethyl polysulfone, acetoxymethyl polysulfone, and t-butyl-oxymethyl polysulfone (Scheme 3). Hydroxymethyl polysulfone sometimes gels under basic hydrolytic conditions and is best obtained by methanolysis of PS-CH,-OAc. Both PS-CH,-OAc and PS-CH20t-Bu are very stable, and provide a way to generate PS-CH2Br on need by cleavage with HBr in acetic acid.Direct oxidations with DMSO or tetrabutyl ammonium dichromate (Scheme 4 ) or indirect oxidations (Scheme 5 ) produce polysulfone with pendent CHO, COzR and P03R groups. Finally, polysulfones with linker arms including, carboxy alkyl, hexaglycol or sulfonamido crowns are described (Scheme 6). The reaction products were characterized by 'H-and 13C-NMR. Double irradiation experiments, proved unequivocally, that the first substitution occurred on the B ring of the bisphenol A moiety (see Table I ) ; the second substitution occurs on the A ring in position a.Thermogravimetric analysis generally shows for all modified polysulfones an extra transition at a lower temperature. The area of this band agrees generally with the values expected from calculated substitution degrees. t Present address: Bar-Ilan University,

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