The hydrophobic effect-a rationalization of the insolubility of nonpolar molecules in water-is centrally important to biomolecular recognition. Despite extensive research devoted to the hydrophobic effect, its molecular mechanisms remain controversial, and there are still no reliably predictive models for its role in proteinligand binding. Here we describe a particularly well-defined system of protein and ligands-carbonic anhydrase and a series of structurally homologous heterocyclic aromatic sulfonamides-that we use to characterize hydrophobic interactions thermodynamically and structurally. In binding to this structurally rigid protein, a set of ligands (also defined to be structurally rigid) shows the expected gain in binding free energy as hydrophobic surface area is added. Isothermal titration calorimetry demonstrates that enthalpy determines these increases in binding affinity, and that changes in the heat capacity of binding are negative. X-ray crystallography and molecular dynamics simulations are compatible with the proposal that the differences in binding between the homologous ligands stem from changes in the number and organization of water molecules localized in the active site in the bound complexes, rather than (or perhaps in addition to) release of structured water from the apposed hydrophobic surfaces. These results support the hypothesis that structured water molecules-including both the molecules of water displaced by the ligands and those reorganized upon ligand binding-determine the thermodynamics of binding of these ligands at the active site of the protein. Hydrophobic effects in various contexts have different structural and thermodynamic origins, although all may be manifestations of the differences in characteristics of bulk water and water close to hydrophobic surfaces.physical-organic | entropy | surface water | benzo-extension | hydration T he hydrophobic effect-the energetically favorable association of nonpolar surfaces in an aqueous solution-often dominates the free energy of binding of proteins and ligands (1-5). Frequently, increasing the nonpolar surface area of a ligand decreases its dissociation constant (K d ; i.e., increases the strength of binding) (6), and simultaneously decreases its equilibrium constant for partitioning from a hydrophobic phase to aqueous solution (K P ) (7). Modern, structure-guided, ligand design has relied upon the "lock-and-key" notion of conformal association between the atoms of the ligand and the binding pocket of a protein; the detailed molecular basis for the hydrophobic effect, however, continues to be poorly understood (1-5). This lack of understanding of the hydrophobic effect prevents accurate prediction of the free energy of binding of proteins and ligands.The first, and currently most pervasive, rationale for the hydrophobic effect was based on studies of the thermodynamics of partitioning of nonpolar solutes from hydrophobic phases (i.e., the gas phase or a hydrophobic liquid phase) into water. The thermodynamics of partitioning of solut...

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This article reports rate constants for thiol-thioester exchange (k (ex)), and for acid-mediated (k (a)), base-mediated (k (b)), and pH-independent (k (w)) hydrolysis of S-methyl thioacetate and S-phenyl 5-dimethylamino-5-oxo-thiopentanoate-model alkyl and aryl thioalkanoates, respectively-in water. Reactions such as thiol-thioester exchange or aminolysis could have generated molecular complexity on early Earth, but for thioesters to have played important roles in the origin of life, constructive reactions would have needed to compete effectively with hydrolysis under prebiotic conditions. Knowledge of the kinetics of competition between exchange and hydrolysis is also useful in the optimization of systems where exchange is used in applications such as self-assembly or reversible binding. For the alkyl thioester S-methyl thioacetate, which has been synthesized in simulated prebiotic hydrothermal vents, k (a) = 1.5 × 10(-5) M(-1) s(-1), k (b) = 1.6 × 10(-1) M(-1) s(-1), and k (w) = 3.6 × 10(-8) s(-1). At pH 7 and 23°C, the half-life for hydrolysis is 155 days. The second-order rate constant for thiol-thioester exchange between S-methyl thioacetate and 2-sulfonatoethanethiolate is k (ex) = 1.7 M(-1) s(-1). At pH 7 and 23°C, with [R″S(H)] = 1 mM, the half-life of the exchange reaction is 38 h. These results confirm that conditions (pH, temperature, pK (a) of the thiol) exist where prebiotically relevant thioesters can survive hydrolysis in water for long periods of time and rates of thiol-thioester exchange exceed those of hydrolysis by several orders of magnitude.

This manuscript describes the use of explosions to power a soft robot-one composed solely of organic elastomers (e.g., silicones). The robot has three pneumatic actuators (pneu-nets) in a tripedal configuration. Explosion of a stoichiometric mixture of methane and oxygen within the microchannels making up the actuators produced hot gas that rapidly inflated the pneu-nets, and caused the robot to launch itself vertically from a flat surface (e.g., to jump). A soft flap embedded in the pneu-net acted as the valve of a passive exhaust system, and allowed multiple sequential actuations. The flame and temperature increase from the explosions are short-lived, and do not noticeably damage the robots over dozens of actuation cycles.1 Soft robots have emerged as a new set of machines capable of manipulation [1][2][3][4] and locomotion. [5][6][7][8] Pneumatic expansion of a network of microchannels (pneu-nets) fabricated in organic elastomers, using low-pressure air (<10 psi; 0.7 atm; 71 kPa), provides a simple method of achieving complex movements: [1, 5] grasping and walking. Despite their advantages (simplicity of fabrication, actuation, and control; low cost; light weight), pneu-nets have the disadvantage that actuation using them is slow, in part because the viscosity of air limits the rate at which the gas can be delivered through tubes to fill and expand the microchannels. Here we demonstrate the rapid actuation of pneu-nets using a chemical reaction (the combustion of methane) to generate explosive bursts of pressure.Although the combustion of hydrocarbons is ubiquitous in the actuation of hard systems (e.g., in the metal cylinder of a diesel or spark-ignited engine [9]), it has not been used to power soft machines. Here, we demonstrate that explosive chemical reactions [10] producing pulses of high temperature gas for pneu-net actuation provides simple, rapid, co-located power generation, and enables motion, in soft robots. In particular, we used the explosive combustion of hydrocarbons triggered by an electrical spark to cause a soft robot to "jump" (a gait previously only demonstrated for hard systems [11][12][13][14][15][16]).We fabricated a tripedal robot ( Fig. 1; Fig. S4) using soft lithography.[1] This robot incorporated a passive valving system (Fig. 1a, inset) that allowed us to (i) pressurize the pneunets easily, (ii) exhaust the product gases automatically (without external control), and (iii) actuate the same pneu-net repeatedly. By actuating all three legs simultaneously, we caused the robot to jump more than 30 times its height in less than 0.2 s, at a maximum vertical velocity of ~3.6 m/s. 2Our choice of explosive chemical reactions for actuation was based on several factors, one being their high volumetric energy density (in units of MJ/L). The energy density of a compressed gas, which we previously used to power soft robots, is ~0.1 MJ/L at 2,900 psi from the potential for mechanical work, w, done by the change in pressure (P), and volume (V) when decompressed to atmospheric pressure; ...

This manuscript describes the use of explosions to power a soft robot-one composed solely of organic elastomers (e.g., silicones). The robot has three pneumatic actuators (pneu-nets) in a tripedal configuration. Explosion of a stoichiometric mixture of methane and oxygen within the microchannels making up the actuators produced hot gas that rapidly inflated the pneu-nets, and caused the robot to launch itself vertically from a flat surface (e.g., to jump). A soft flap embedded in the pneu-net acted as the valve of a passive exhaust system, and allowed multiple sequential actuations. The flame and temperature increase from the explosions are short-lived, and do not noticeably damage the robots over dozens of actuation cycles.1 Soft robots have emerged as a new set of machines capable of manipulation [1][2][3][4] and locomotion. [5][6][7][8] Pneumatic expansion of a network of microchannels (pneu-nets) fabricated in organic elastomers, using low-pressure air (<10 psi; 0.7 atm; 71 kPa), provides a simple method of achieving complex movements: [1, 5] grasping and walking. Despite their advantages (simplicity of fabrication, actuation, and control; low cost; light weight), pneu-nets have the disadvantage that actuation using them is slow, in part because the viscosity of air limits the rate at which the gas can be delivered through tubes to fill and expand the microchannels. Here we demonstrate the rapid actuation of pneu-nets using a chemical reaction (the combustion of methane) to generate explosive bursts of pressure.Although the combustion of hydrocarbons is ubiquitous in the actuation of hard systems (e.g., in the metal cylinder of a diesel or spark-ignited engine [9]), it has not been used to power soft machines. Here, we demonstrate that explosive chemical reactions [10] producing pulses of high temperature gas for pneu-net actuation provides simple, rapid, co-located power generation, and enables motion, in soft robots. In particular, we used the explosive combustion of hydrocarbons triggered by an electrical spark to cause a soft robot to "jump" (a gait previously only demonstrated for hard systems [11][12][13][14][15][16]).We fabricated a tripedal robot ( Fig. 1; Fig. S4) using soft lithography.[1] This robot incorporated a passive valving system (Fig. 1a, inset) that allowed us to (i) pressurize the pneunets easily, (ii) exhaust the product gases automatically (without external control), and (iii) actuate the same pneu-net repeatedly. By actuating all three legs simultaneously, we caused the robot to jump more than 30 times its height in less than 0.2 s, at a maximum vertical velocity of ~3.6 m/s. 2Our choice of explosive chemical reactions for actuation was based on several factors, one being their high volumetric energy density (in units of MJ/L). The energy density of a compressed gas, which we previously used to power soft robots, is ~0.1 MJ/L at 2,900 psi from the potential for mechanical work, w, done by the change in pressure (P), and volume (V) when decompressed to atmospheric pressure; ...