Small-molecule autocatalysis drives compartment growth, competition and reproduction.

Sustained autocatalysis coupled to compartment growth and division is a key step in the origin of life, but an experimental demonstration of this phenomenon in an artificial system has previously proven elusive. We show that autocatalytic reactions within compartments-when autocatalysis, and reactant and solvent exchange outpace product exchange-drive osmosis and diffusion, resulting in compartment growth. We demonstrate, using the formose reaction compartmentalized in aqueous droplets in an emulsion, that compartment volume can more than double. Competition for a common reactant (formaldehyde) causes variation in droplet growth rate based on the composition of the surrounding droplets. These growth rate variations are partially transmitted after selective division of the largest droplets by shearing, which converts growth-rate differences into differences in droplet frequency. This shows how a combination of properties of living systems (growth, division, variation, competition, rudimentary heredity and selection) can arise from simple physical-chemical processes and may have paved the way for the emergence of evolution by natural selection.

Final Products of One-Electron Oxidation of Cyclic Dipeptides Containing Methionine Investigated by IRMPD Spectroscopy: Does the Free Radical Choose the Final Compound?

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and the hydroxyl radical (•OH) have specific functions in biological processes, while their uncontrolled production and reactivity are known to be determining factors in pathophysiology. Methionine (Met) residues act as endogenous antioxidants, when they are oxidized into methionine sulfoxide (MetSO), thus depleting ROS and protecting the protein. We employed tandem mass spectrometry combined with IR multiple photon dissociation spectroscopy to study the oxidation induced by OH radicals produced by γ radiolysis on model cyclic dipeptides c(LMetLMet), c(LMetDMet), and c(GlyMet). Our aim was to characterize the geometries of the oxidized peptides in the gas phase and to understand the relationship between the structure of the 2-center 3-electron (2c-3e) free radical formed in the first step of the oxidation process and the final compound. Density functional theory calculations were performed to characterize the lowest energy structures of the final product of oxidation and to interpret the IR spectra. Collision-induced dissociation tandem mass spectrometry (CID-MS2) experiments of oxidized c(LMetLMet)H+ and c(LMetDMet)H+ led to the loss of one or two oxidized sulfenic acid molecules, indicating that the addition of one or two oxygen atoms occurs on the sulfur atom of both methionine side chains and no sulfone formation was observed. The CID-MS2 fragmentation mass spectrum of oxidized c(GlyMet)H+ showed only the loss of one oxidized sulfenic acid molecule. Thus, the final products of oxidation are the same regardless of the structure of the precursor sulfur-centered free radical.

Structure of Proton-Bound Methionine and Tryptophan Dimers in the Gas Phase Investigated with IRMPD Spectroscopy and Quantum Chemical Calculations.

The structures of three proton-bound dimers (Met2H+, MetTrpH+, and Trp2H+) are investigated in the gas phase with infrared multiple photon disassociation (IRMPD) spectroscopy in combination with quantum chemical calculations. Their IRMPD spectra in the range of 600-1850 cm-1 are obtained experimentally using an FT-ICR mass spectrometer and the CLIO free electron laser as an IR light source. The most abundant conformers are elucidated by comparing the IRMPD spectra with harmonic frequencies obtained at the B3LYP-GD3BJ/6-311++G** level of theory. Discrepancies between the experimental and theoretical data in the region of 1500-1700 cm-1 are attributed to the anharmonicity of the amino bending modes. We confirm the result of a previous IRMPD study that the structure of gas-phase Trp2H+ is charge-solvated but find that there are more stable structures than originally reported (Feng, R.; Yin, H.; Kong, X. Rapid Commun. Mass Spectrom. 2016, 30, 24-28). In addition, gas-phase Met2H+ and MetTrpH+ have been revealed to have charge-solvated structures. For all three dimers, the most stable conformer is found to be of type A. The spectrum of Met2H+, however, cannot be explained without some abundance of type B charge-solvated conformers as well as salt-bridged structures.

An IRMPD spectroscopic and computational study of protonated guanine-containing mismatched base pairs in the gas phase.

Infrared multiple photon dissociation (IRMPD) spectroscopy has been used to probe the structures of the three protonated base-pair mismatches containing 9-ethylguanine (9eG) in the gas phase. Computational chemistry has been used to determine the relative energies and compute the infrared spectra of these complexes. By comparing the IRMPD spectra with the computed spectra, in all cases, it was possible to deduce that what was observed experimentally were the lowest energy computed structures. The protonated complex between 9eG and 1-methylthymine (1mT) is protonated at N7 of 9eG-the most basic site of all three bases in this study-and bound in a Hoogsteen type structure with two hydrogen bonds. The experimental IRMPD spectrum for the protonated complex between 9eG and 9-methyladenine (9mA) is described as arising from a combination of the two lowest energy structures, both which are protonated at N1 of adenine and each containing two hydrogen bonds with 9eG being the acceptor of both. The protonated dimer of 9eG is protonated at N7 with an N7-H+-N7 ionic hydrogen bond. It also contains an interaction between a C-H of protonated guanine and the O6 carbonyl of neutral guanine which is manifested in a slight red shift of that carbonyl stretch. The protonated 9eG/9mA structures have been previously identified by X-ray crystallography in RNA and are contained within the protein database.

Reactions of Thiiranium and Sulfonium Ions with Alkenes in the Gas Phase.

Ion-molecule reactions between thiiranium ion 11 (m/z 213) and cyclohexene and cis-cyclooctene resulted in the formation of addition products 17a and 17b (m/z 295 and m/z 323, respectively) via an electrophilic addition pathway. Associative π-ligand exchange involving direct transfer of the PhS+ moiety, which has been observed for analogous seleniranium ions in the gas phase, did not occur despite previous solution experiments suggesting it as a valid pathway. DFT calculations at the M06-2X/def2-TZVP level of theory showed high barriers for the exchange reaction, while the addition pathway was more plausible. Further support for this pathway was provided with Hammett plots showing the rate of reaction to increase as the benzylic position of thiiranium ion derivatives became more electrophilic (ρ = +1.69; R2 = 0.974). The more reactive isomeric sulfonium ion 22 was discounted as being responsible for the observed reactivity with infrared spectroscopy and DFT calculations suggesting little possibility for isomerization. To further explore the differences in reactivity, thiiranium ion 25 and sulfonium ion 27 were formed independently, with the latter ion reacting over 260 times faster toward cis-cyclooctene than the thiiranium ion rationalized by calculations suggesting a barrierless pathway for sulfonium ion 27 to react with the cycloalkene.

Hydrogen bonding in alkali metal cation-bound i-motif-like dimers of 1-methyl cytosine: an IRMPD spectroscopic and computational study.

The structures of alkali metal cation bound 1-methylcytosine (1-mCyt) dimers were explored using vibrational spectroscopy in the form of infrared multiple photon dissociation (IRMPD) spectroscopy and by computational methods. For the smaller alkali metal cations, Li+ and Na+, only non-hydrogen bonded symmetric anti-parallel structures were observed in agreement with the lowest energy computed structures. For K+, Rb+, and Cs+ the vibrational spectra in the N-H stretch region showed strong evidence for hydrogen bonding in agreement with the lowest energy structures which contained hydrogen bonding interactions between the amine group of one cytosine and the carbonyl oxygen of the other cytosine. The lowest energy structures for these complexes were compared to previously studied cytosine complexes [(Cyt)2M]+ where M = Li, Na, and K. The calculations are in agreement that only the non-hydrogen bonded structures would be observed for these cytosine complexes.

The structures and properties of anionic tryptophan complexes.

The physicochemical properties of [Trpn-H]- and [TrpnCl]- (n = 1, 2) have been investigated in a combined computational and experimental infrared multiple dissociation (IRMPD) study. IRMPD spectra within the 850-1900 cm-1 region indicate that deprotonation is localized on the carboxylic acid moiety in [Trpn-H]- clusters. A combination of hydrogen bonding and higher order charge-quadrupole interactions appear to influence cluster geometries for all investigated systems. Calculated global minimum and low energy geometries of [TrpCl]- and [Trp2Cl]- clusters favour coordination of the halide by the indole NH. [Trp2-H]- and [Trp2Cl]- exhibit additional π-π interactions between the heterocyclic side chains.