Mapping behavioral specifications to model parameters in synthetic biology

With recent improvements of protocols for the assembly of transcriptional parts, synthetic biological devices can now more reliably be assembled according to a given design. The standardization of parts open up the way for in silico design tools that improve the construct and optimize devices with respect to given formal design specifications. The simplest such optimization is the selection of kinetic parameters and protein abundances such that the specified design constraints are robustly satisfied. In this work we address the problem of determining parameter values that fulfill specifications expressed in terms of a functional on the trajectories of a dynamical model. We solve this inverse problem by linearizing the forward operator that maps parameter sets to specifications, and then inverting it locally. This approach has two advantages over brute-force random sampling. First, the linearization approach allows us to map back intervals instead of points and second, every obtained value in the parameter region is satisfying the specifications by construction. The method is general and can hence be incorporated in a pipeline for the rational forward design of arbitrary devices in synthetic biology

Propene Oxidation on V₄O₁₁⁻ Cluster: Reaction Dynamics to Acrolein

Oxidation dynamics of propene (CH3CHCH2) to acrolein (CH2CHCHO) on the anionic vanadium oxide cluster V4O11− is investigated with the first-principle density functional calculations, providing an interpretation to V4O11− + propene → V4O10H2− + C3H6O observed in the photochemical reactions (Li, S.; Mirabal, A.; Demuth, J.; Wöste, L.; Siebert, T. J. Am. Chem. Soc. 2008, 130, 16832). The complicated energy surface of the reaction between V4O11− and propene is explored, and the stepwise dynamic processes for propene to acrolein are proposed. Initially, propene is captured by V4O11− with a hydrogen bond CH (methyl group in propene)···O (dioxo group in V4O11−), then undergoes dehydrogenation along this hydrogen bond to form a π-allyl radical. After the redehydrogenation of the π-allyl and oxygen transfer from the vanadium oxide cluster, acrolein is eventually produced together with four isomers of V4O10H2− in the different reaction paths. During this process, the negative charge is found to transfer between the hydrocarbon and the vanadium oxide moieties

Temperature Dependence of Catalyst-Free Chirality-Controlled Single-Walled Carbon Nanotube Growth from Organic Templates

The temperature dependence of catalyst-free single-walled carbon nanotube (SWCNT) growth from organic molecular precursors is investigated using DFTB quantum chemical molecular dynamics simulations and DFT calculations. Growth of (6,6)-SWCNTs from [6]­cycloparaphenylene ([6]­CPP) template molecules was simulated at 300, 500, and 800 K using acetylene (C₂H₂) and ethynyl radicals (C₂H) as growth agents. The highest growth rates were observed with C₂H at 500 K. Higher temperatures lead to increased defect formation in the SWCNT structure during growth. Such defects, which cause the loss of SWCNT chirality control, were driven by radical addition reactions with inherently low kinetic barriers. We therefore propose that lower temperature is optimal for the C₂H radical mechanism of SWCNT growth, and predict the existence of an optimum SWCNT growth temperature that balances the rates of growth and defect formation at a given C₂H/C₂H₂ ratio

Single-walled Carbon Nanotube Growth from Chiral Carbon Nanorings: Prediction of Chirality and Diameter Influence on Growth Rates

Catalyst-free, chirality-controlled growth of chiral and zigzag single-walled carbon nanotubes (SWCNTs) from organic precursors is demonstrated using quantum chemical simulations. Growth of (4,3), (6,5), (6,1), (10,1) and (8,0) SWCNTs was induced by ethynyl radical (C₂H) addition to organic precursors. These simulations show a strong dependence of the SWCNT growth rate on the chiral angle, θ. The SWCNT diameter however does not influence the SWCNT growth rate under these conditions. This agreement with a previously proposed screw-dislocation-like model of transition metal-catalyzed SWCNT growth rates [Ding, F.; Proc. Natl. Acad. Sci. 2009, 106, 2506] indicates that the SWCNT growth rate is an intrinsic property of the SWCNT edge itself. Conversely, we predict that the rate of SWCNT growth <i>via</i> Diels–Alder cycloaddition of C₂H₂ is strongly influenced by the diameter of the SWCNT. We therefore predict the existence of a maximum growth rate for an optimum diameter/chirality combination at a given C₂H/C₂H₂ ratio. We also find that the ability of a SWCNT to avoid defect formation during growth is an intrinsic quality of the SWCNT edge

Revealing the Dual Role of Hydrogen for Growth Inhibition and Defect Healing in Polycyclic Aromatic Hydrocarbon Formation: QM/MD Simulations

Quantum mechanical molecular dynamics simulations are employed to reveal the influence of hydrogen on polycyclic aromatic hydrocarbon (PAH) formation in oxygen-lean combustion. While higher hydrogen concentration leads to the inhibition of PAH growth, it simultaneously facilitates pentagon and heptagon defect healing, leading to thermodynamically more stable PAH fragments with more hexagons. We therefore propose the existence of an optimal H/C ratio that facilitates the growth of all-hexagon-containing PAH species. Analysis of the PAH edge reconstruction in our simulations shows a near-equal ratio of armchair and zigzag edge structures. As armchair edge structures are thermodynamically considerably more stable than zigzag edge structures, the present simulations show that both kinetic and thermodynamic factors are needed to understand PAH/graphene edge reconstruction

Single-walled Carbon Nanotube Growth from Chiral Carbon Nanorings: Prediction of Chirality and Diameter Influence on Growth Rates

Catalyst-free, chirality-controlled growth of chiral and zigzag single-walled carbon nanotubes (SWCNTs) from organic precursors is demonstrated using quantum chemical simulations. Growth of (4,3), (6,5), (6,1), (10,1) and (8,0) SWCNTs was induced by ethynyl radical (C₂H) addition to organic precursors. These simulations show a strong dependence of the SWCNT growth rate on the chiral angle, θ. The SWCNT diameter however does not influence the SWCNT growth rate under these conditions. This agreement with a previously proposed screw-dislocation-like model of transition metal-catalyzed SWCNT growth rates [Ding, F.; Proc. Natl. Acad. Sci. 2009, 106, 2506] indicates that the SWCNT growth rate is an intrinsic property of the SWCNT edge itself. Conversely, we predict that the rate of SWCNT growth <i>via</i> Diels–Alder cycloaddition of C₂H₂ is strongly influenced by the diameter of the SWCNT. We therefore predict the existence of a maximum growth rate for an optimum diameter/chirality combination at a given C₂H/C₂H₂ ratio. We also find that the ability of a SWCNT to avoid defect formation during growth is an intrinsic quality of the SWCNT edge

Asymmetric Phase-Transfer Catalysis with Homo- and Heterochiral Quaternary Ammonium Salts: A Theoretical Study

A thorough theoretical study of phase-transfer quaternary ammonium catalysts designed by the Maruoka group has been performed in an attempt to gain better understanding of the properties and catalytic behavior of the homo- and heterochiral forms of these systems. The conformationally flexible analogue is found to easily undergo interconversion from the homo- to the heterochiral form driven by the higher thermodynamic stability of the heterochiral isomer and resulting in alternation in catalytic behavior. Theoretical calculations of ¹H NMR spectra of the two isomers for different model systems are in good agreement with the experimental data, allowing us to conclude that the upfield shift of signals for the benzylic protons in the heterochiral form could be explained by an increase in the shielding effect of the aromatic parts of the system around these protons due to the conformational changes. By applying the automated transition state (TS) search procedure for the alkylation of glycine derivatives catalyzed by the homo-/heterochiral form of a conformationally rigid analogue, we were able to locate more than 40 configurations of the TS structures. In brief, the homochiral form was theoretically confirmed to catalyze the formation of the predominant <i>R</i>-product, while for the heterochiral form the catalytic activity is found to depend on two factors: (i) formation of a tight ion pair between the catalyst and the glycine derivative, which results in a decrease in the reaction rate, in agreement with the experimental data, and formation of only the <i>R</i>-product, and (ii) the possibility that the reaction occurs without the initial formation of the ion pair or after its dissociation, in which case the formation of an <i>S</i>-product is predominant. The combined effects of both factors would explain the lower reaction rate and the poor enantioselectivity observed experimentally for the heterochiral form

Single-walled Carbon Nanotube Growth from Chiral Carbon Nanorings: Prediction of Chirality and Diameter Influence on Growth Rates

Catalyst-free, chirality-controlled growth of chiral and zigzag single-walled carbon nanotubes (SWCNTs) from organic precursors is demonstrated using quantum chemical simulations. Growth of (4,3), (6,5), (6,1), (10,1) and (8,0) SWCNTs was induced by ethynyl radical (C₂H) addition to organic precursors. These simulations show a strong dependence of the SWCNT growth rate on the chiral angle, θ. The SWCNT diameter however does not influence the SWCNT growth rate under these conditions. This agreement with a previously proposed screw-dislocation-like model of transition metal-catalyzed SWCNT growth rates [Ding, F.; Proc. Natl. Acad. Sci. 2009, 106, 2506] indicates that the SWCNT growth rate is an intrinsic property of the SWCNT edge itself. Conversely, we predict that the rate of SWCNT growth <i>via</i> Diels–Alder cycloaddition of C₂H₂ is strongly influenced by the diameter of the SWCNT. We therefore predict the existence of a maximum growth rate for an optimum diameter/chirality combination at a given C₂H/C₂H₂ ratio. We also find that the ability of a SWCNT to avoid defect formation during growth is an intrinsic quality of the SWCNT edge

Single-walled Carbon Nanotube Growth from Chiral Carbon Nanorings: Prediction of Chirality and Diameter Influence on Growth Rates

Catalyst-free, chirality-controlled growth of chiral and zigzag single-walled carbon nanotubes (SWCNTs) from organic precursors is demonstrated using quantum chemical simulations. Growth of (4,3), (6,5), (6,1), (10,1) and (8,0) SWCNTs was induced by ethynyl radical (C₂H) addition to organic precursors. These simulations show a strong dependence of the SWCNT growth rate on the chiral angle, θ. The SWCNT diameter however does not influence the SWCNT growth rate under these conditions. This agreement with a previously proposed screw-dislocation-like model of transition metal-catalyzed SWCNT growth rates [Ding, F.; Proc. Natl. Acad. Sci. 2009, 106, 2506] indicates that the SWCNT growth rate is an intrinsic property of the SWCNT edge itself. Conversely, we predict that the rate of SWCNT growth <i>via</i> Diels–Alder cycloaddition of C₂H₂ is strongly influenced by the diameter of the SWCNT. We therefore predict the existence of a maximum growth rate for an optimum diameter/chirality combination at a given C₂H/C₂H₂ ratio. We also find that the ability of a SWCNT to avoid defect formation during growth is an intrinsic quality of the SWCNT edge

Quantum Chemical Simulation of Carbon Nanotube Nucleation on Al₂O₃ Catalysts via CH₄ Chemical Vapor Deposition

We present quantum chemical simulations demonstrating how single-walled carbon nanotubes (SWCNTs) form, or “nucleate”, on the surface of Al₂O₃ nanoparticles during chemical vapor deposition (CVD) using CH₄. SWCNT nucleation proceeds via the formation of extended polyyne chains that only interact with the catalyst surface at one or both ends. Consequently, SWCNT nucleation is not a surface-mediated process. We demonstrate that this unusual nucleation sequence is due to two factors. First, the π interaction between graphitic carbon and Al₂O₃ is extremely weak, such that graphitic carbon is expected to desorb at typical CVD temperatures. Second, hydrogen present at the catalyst surface actively passivates dangling carbon bonds, preventing a surface-mediated nucleation mechanism. The simulations reveal hydrogen’s reactive chemical pathways during SWCNT nucleation and that the manner in which SWCNTs form on Al₂O₃ is fundamentally different from that observed using “traditional” transition metal catalysts