Accumulation of formamide in hydrothermal pores to form prebiotic nucleobases

Formamide is one of the important compounds from which prebiotic molecules can be synthesized, provided that its concentration is sufficiently high. For nucleotides and short DNA strands, it has been shown that a high degree of accumulation in hydrothermal pores occurs, so that temperature gradients might play a role in the origin of life [Baaske P, et al. (2007) Proc Natl Acad Sci USA 104(22):9346−9351]. We show that the same combination of thermophoresis and convection in hydrothermal pores leads to accumulation of formamide up to concentrations where nucleobases are formed. The thermophoretic properties of aqueous formamide solutions are studied by means of Infrared Thermal Diffusion Forced Rayleigh Scattering. These data are used in numerical finite element calculations in hydrothermal pores for various initial concentrations, ambient temperatures, and pore sizes. The high degree of formamide accumulation is due to an unusual temperature and concentration dependence of the thermophoretic behavior of formamide. The accumulation fold in part of the pores increases strongly with increasing aspect ratio of the pores, and saturates to highly concentrated aqueous formamide solutions of ∼85 wt% at large aspect ratios. Time-dependent studies show that these high concentrations are reached after 45–90 d, starting with an initial formamide weight fraction of 10−3 wt % that is typical for concentrations in shallow lakes on early Earth

Thermophoretic Properties of Aqueous Formamide Solutions and Accumulation in Hydrothermal Pores

Formamide is one of the important compounds from which prebiotic molecules can be synthesized, provided that its concentration is sufficiently high. For nucleotides and short DNA strands it has been shown that a high degree of accumulation in hydrothermal pores occurs, so that temperature gradients might play a role in the 'origin-of-life' [1]. We show that the same combination of thermophoresis and convection in hydrothermal pores leads to accumulation of formamide up to concentrations where nucleobases are formed. The thermophoretic properties of aqueous formamide solutions are studied by means of Infra-Red Thermal Diffusion Forced Rayleigh Scattering. These data are used in numerical finite-element calculations in hydrothermal pores for various initial concentrations, ambient temperatures, and pore sizes. The high degree of formamide accumulation is due to an unusual temperature and concentration dependence of the thermophoretic behaviour of formamide. The accumulation-fold in part of the pores increases strongly with increasing aspect ratio of the pores, and saturates to highly concentrated aqueous formamide solutions of approximately 85 wt% at large aspect ratios. Time dependent studies show that these high concentrations are reached after 45-90 days, starting with an initial formamide weight fraction of $10-3 wt% that is typical for concentrations in shallow lakes on early earth [2].References1. P. Baaske, F. M. Weinert, S. Duhr, K. H. Lemke, M. J. Russell and D. Braun, et al., P. Natl. Acad. Sci. USA, Vol. 104, No. 22 (2007) pp. 9346-9351.2. D. Niether, D. Afanasenkau, J. K. G. Dhont and S. Wiegand, PNAS, accepted, (2016)

Thermophoresis of biological and biocompatible systems

Thermophoresis, or thermodiffusion, is mass transport driven by a temperature gradient. This work focuses on thermodiffusion in a biological context, where there are two major applications for the effect: accumulation of a component in microfluidic devices through a combination of thermodiffusion and convection, and monitoring of protein binding reactions through the sensitivity of thermodiffusion to complex formation.Both applications are investigated, the first as an accumulation process in the context of origin-of-life theories and the second in light of the question what we can learn from the observed changes in thermodiffusion about modifications of the hydration shell upon complex formation. While thermodiffusion in non-polar liquids can be predicted with reasonable accuracy, the description of aqueous systems is complicated as their concentration and temperature dependence is often anomalous. The underlying goal of this work is to gain a better understanding of the interactions between components in an aqueous mixture and how they influence thermodiffusion.We find that the temperature dependence of a solute's thermodiffusion correlates with its hydrophilicity and argue that the temperature sensitivity of hydrogen bonds, which dominate the interactions in aqueous solutions, might induce a temperature dependence of the chemical potential. Such a temperature dependence is as of yet not considered in theoretical descriptions of thermodiffusion. Numerical calculations show that the thermophoretic accumulation process, as of yet only considered for the formation of RNA, can accumulate formamide to high concentrations that would allow the formation of prebiotic molecules. A heuristic model is developed to illuminate the mechanism behind the accumulation. Cyclodextrins and streptavidin were investigated as model systems for biological complexes. It is feasible that the exquisite sensitivity of thermodiffusion to interactions with the surrounding solvent allows inferences about changes in the protein's hydration shell upon complex formation. Preliminary measurements on streptavidin-biotin show a decreased hydrophilicity of the complex, which is in qualitative agreement with increased entropy of the hydration shell upon complex formation calculated from calorimetric and neutron scattering experiments

Thermodiffusion and hydrolysis of 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)

Presently, microfluidic traps are designed mimicking the environment of hydrothermal pores, where a combination of thermophoresis and convection leads to accumulation so that high concentrations of organic matter can be reached. Such a setup is interesting in the context of the origin of life to observe accumulation and possible further synthesis of small organic molecules or prebiotic molecules such as nucleotides or RNA-fragments, but could also be used to replicate DNA-strands. The addition of coupling agents for the activation of carboxyl or phosphate groups such as 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and EDC-hydrochloride (EDC-HCl) is necessary in order to speed up the process. This work characterizes the thermophoretic properties of EDC and EDC-HCl needed to optimize the design of the traps. At p H 4-6 spontaneous hydrolysis of EDC is observed, which also leads to a neutralisation of the p H. In order to evaluate the thermodiffusion measurements the rate constants were measured at 23 and C and the activation energy of the hydrolysis calculated

INFLUENCE OF THE HYDROPHOBIC/HYDROPHILIC INTERPLAY ON THERMODIFFUSION

The hydration of hydrophobic solutes remains still illusive despite the long history of research. Often hydrophobic hydration is explained in terms of a balance between the loss in entropy due to cavity formation to accommodate the hydrophobic molecule and the gain in enthalpy due to attraction between the solute and solvent molecules [1]. This entropic-enthalpic compensation mechanism is often found in the context of biochemical reactions and apparently thermodiffusion is especially sensitive to this balance. We take a closer look into the mechanism by studying systematically hydrophilic and more hydrophobic small molecules as function of temperature and concentration. We elucidate the often found typical temperature dependence of the Soret coefficient of solute molecules in water and relate the empirical parameters with the number and the strength of hydrogen bonds [2]. Using a linear correlation between those parameters, we are able to reduce the number of adjustable parameters to two. We observe a clear correlation of the temperature and concentration dependence of the Soret coefficient with the hydrophilicity, which can be quantitatively described by the logarithm of the 1-octanol/water partition coefficient P, which is a measure for the hydrophilicity/hydrophobicity balance of a solute for numerous systems [3]. It is often used to model the transport of a compound in the environment or to screen for potential pharmaceutical compounds. We give an intuitive picture explaining the correlation between log P and the temperature sensitivity of the Soret coefficient. Finally we discuss a route for a more sophisticated hydrophilicity scale. REFERENCES[1] S. Liese et al., ACS Nano, 11 702 (2017).[2] Niether, D., et al., Langmuir, 33, 8483(2017).[3] Niether, D., et al., Physical Chemistry Chemical Physics, 20, 1012(2018)

Thermophoresis of biological and biocompatible compounds in aqueous solution

With rising popularity of Microscale Thermophoresis for the characterisation of protein-ligand binding reactions and possible applications in microfluidic devices, there is a growing interest in considering thermodiffusion in the context of life sciences. But although the understanding of thermodiffusion in non-polar mixtures has grown rapidly in recent years, predictions for associated mixtures like aqueous solutions remain challenging. This review aims to give an overview of the literature on thermodiffusion in aqueous systems, show the difficulties in theoretical description that arise from the non-ideal behaviour of water-mixtures, and highlight the relevance of thermodiffusion in a biological context. We find that the thermodiffusion in aqueous systems is dominated by contributions from heat of transfer, hydrogen bond interactions and charge effects. However, the separation of these effects is often difficult, especially in case of biological systems where a systematic exclusion of contributions may not be feasible

Heuristic Approach to Understanding the Accumulation Process in Hydrothermal Pores

One of the central questions of humankind is: which chemical and physical conditions are necessary to make life possible? In this “origin-of-life” context, formamide plays an important role, because it has been demonstrated that prebiotic molecules can be synthesized from concentrated formamide solutions. Recently, it could be shown, using finite-element calculations combining thermophoresis and convection processes in hydrothermal pores, that sufficiently high formamide concentrations could be accumulated to form prebiotic molecules (Niether et al. (2016)). Depending on the initial formamide concentration, the aspect ratio of the pores, and the ambient temperature, formamide concentrations up to 85 wt % could be reached. The stationary calculations show an effective accumulation, only if the aspect ratio is above a certain threshold, and the corresponding transient studies display a sudden increase of the accumulation after a certain time. Neither of the observations were explained. In this work, we derive a simple heuristic model, which explains both phenomena. The physical idea of the approach is a comparison of the time to reach the top of the pore with the time to cross from the convective upstream towards the convective downstream. If the time to reach the top of the pore is shorter than the crossing time, the formamide molecules are flushed out of the pore. If the time is long enough, the formamide molecules can reach the downstream and accumulate at the bottom of the pore. Analysing the optimal aspect ratio as function of concentration, we find that, at a weight fraction of w = 0 . 5 , a minimal pore height is required for effective accumulation. At the same concentration, the transient calculations show a maximum of the accumulation rate

Correlation between thermophoretic behavior and hydrophilicity for various alcohols

Recent experiments for various amides and sugars showed a clear correlation of the temperature dependence of the Soret coefficient with the hydrophilicity, quantitatively described by the logarithm of the 1-octanol/water partition coefficient logP . This coefficient is a measure for the hydrophilicity/hydrophobicity balance of a solute and is often used to model the transport of a compound in the environment or to screen for potential pharmaceutical compounds. In order to validate whether this concept works also for other water soluble molecules we investigated systematically the thermophoresis of mono- and polyhydric alcohols. As experimental method we use a holographic grating technique called infrared Thermal Diffusion Forced Rayleigh Scattering (IR-TDFRS). Experiments showed that the temperature dependence of the Soret coefficient of polyhydric alcohols also correlates with logP and lies on the same master plot as amides and sugars