One‐electron redox properties of DNA nucleobases and common tautomers

The redox properties of DNA play an influential role in several important processes such as DNA mutation and the interaction of DNA with drugs. Structural changes in DNA nucleobases from its canonical form to its tautomeric forms can alter these properties and may lead to DNA mutation due to altered base‐pairing properties. Experimental results for the standard value of DNA redox properties vary due to choice of methodology and solvent. Theoretical determination of these properties is helpful in pinpointing standard values but still vary depending on methodology and chosen experimental benchmark. However, it is of importance to identify the overall trend of electron mobility within DNA while providing reliable standard values for redox reactions. In this work, we present the results of theoretical calculations for redox properties. Using the thermodynamic cycle, we can approximate reliable values. We report the electron affinities, ionization potentials, and redox potential for the canonical DNA nucleobases and their rare tautomers. For each of these properties, we evaluate its overall trend to gain a greater understanding of the role that electron attachment and electron mobility have within the DNA strand. All calculations are computed at the M06‐2X/6–31++G(d,p) level of theory. © 2014 Wiley Periodicals, Inc.     

Unexpected Self‐Assembly of a Homochiral Metallosupramolecular M4L4 Catenane

Two enantiomerically pure 9,9′‐spirobifluorene‐based bis(pyridine) ligands 1 and 2 were prepared to study their self‐assembly behavior upon coordination to cis‐protected palladium(II) ions. Whereas the sterically more demanding ligand, 2 , gave rise to the expected dinuclear metallosupramolecular M₂L₂ rhombi, the sterically less demanding ligand, 1 , acts as a template to give rise to a homochiral metallosupramolecular M₄L₄ catenane.     

Enantiomerically Pure [M6L12] or [M12L24] Polyhedra from Flexible Bis(Pyridine) Ligands

Coordination‐driven self‐assembly is one of the most powerful strategies to prepare nanometer‐sized discrete (supra)molecular assemblies. Herein, we report on the use of two constitutionally isomeric BINOL‐based bis(pyridine) ligands for this purpose. Upon coordination to Pd^II ions these self‐assemble into enantiomerically pure endo‐ and exo‐functionalized hexa‐ and dodecanuclear metallosupramolecular spheres with a chiral skeleton depending on the substitution pattern of the BINOL core. These aggregates were characterized by NMR, MS, DLS, TEM, and EELS as well as ECD. Furthermore, experimental ECD data could be compared to those obtained from theoretical simulations using a simplified Tamm–Dancoff approximation to time‐dependent DFT to rationalize the extraordinary high molar circular dichroisms. Despite the rotational freedom around the central aryl–aryl bond of these ligands, the self‐assembly process happens completely selective in a “narcissistic” self‐recognition manner.     

Inactivation of microbial arginine deiminases by L-canavanine

Arginine deiminase (ADI) catalyzes the hydrolytic conversion of L-arginine to ammonia and L-citrulline as part of the energy-producing L-arginine degradation pathway. The chemical mechanism for ADI catalysis involves initial formation and subsequent hydrolysis of a Cys-alkylthiouronium ion intermediate. The structure of the Pseudomonas aeruginosa ADI-(L-arginine) complex guided the design of arginine analogs that might react with the ADIs to form inactive covalent adducts during catalytic turnover. One such candidate is L-canavanine, in which an N-methylene of L-arginine is replaced by an N-O. This substance was shown to be a slow substrate-producing O-ureido-L-homoserine. An in depth kinetic and mass spectrometric analysis of P. aeruginosa ADI inhibition by L-canavanine showed that two competing pathways are followed that branch at the Cys-alkylthiouronium ion intermediate. One pathway leads to direct formation of O-ureido-L-homoserine via a reactive thiouronium intermediate. The other pathway leads to an inactive form of the enzyme, which was shown by chemical model and mass spectrometric studies to be a Cys-alkylisothiourea adduct. This adduct undergoes slow hydrolysis to form O-ureido-L-homoserine and regenerated enzyme. In contrast, kinetic and mass spectrometric investigations demonstrate that the Cys-alkylthiouronium ion intermediate formed in the reaction of L-canavanine with Bacillus cereus ADI partitions between the product forming pathway (O-ureido-L-homoserine and free enzyme) and an inactivation pathway that leads to a stable Cys-alkylthiocarbamate adduct. The ADIs from Escherichia coli, Burkholderia mallei, and Giardia intestinalis were examined in order to demonstrate the generality of the L-canavanine slow substrate inhibition and to distinguish the kinetic behavior that defines the irreversible inhibition observed with the B. cereus ADI from the time controlled inhibition observed with the P. aeruginosa, E. coli, B. mallei, and G. intestinalis ADIs.     

Unambiguous Automata

We give a new presentation of two results concerning synchronized automata. The first one gives a linear bound on the synchronization delay of complete local automata. The second one gives a cubic bound for the minimal length of a synchronizing pair in a complete synchronized unambiguous automaton. The proofs are based on results on unambiguous monoids of relations. Research supported by the Academy of Finland grant 211967 and by the Turku University Foundation grant.     

N−X⋅⋅⋅O−N Halogen Bonds in Complexes of N-Haloimides and Pyridine-N-oxides: A Large Data Set Study

N−X⋅⋅⋅⁻O−N⁺ halogen-bonded systems formed by 27 pyridine N-oxides (PyNOs) as halogen-bond (XB) acceptors and two N-halosuccinimides, two N-halophthalimides, and two N-halosaccharins as XB donors are studied in silico, in solution, and in the solid state. This large set of data (132 DFT optimized structures, 75 crystal structures, and 168 ¹H NMR titrations) provides a unique view to structural and bonding properties. In the computational part, a simple electrostatic model (SiElMo) for predicting XB energies using only the properties of halogen donors and oxygen acceptors is developed. The SiElMo energies are in perfect accord with energies calculated from XB complexes optimized with two high-level DFT approaches. Data from in silico bond energies and single-crystal X-ray structures correlate; however, data from solution do not. The polydentate bonding characteristic of the PyNOs’ oxygen atom in solution, as revealed by solid-state structures, is attributed to the lack of correlation between DFT/solid-state and solution data. XB strength is only slightly affected by the PyNO oxygen properties [(atomic charge (Q), ionization energy (I_s,min) and local negative minima (V_s,min)], as the σ-hole (V_s,max) of the donor halogen is the key determinant leading to the sequence N-halosaccharin>N-halosuccinimide>N-halophthalimide on the XB strength.     

Size- and structure-selective noncovalent recognition of saccharides by tetraethyl and tetraphenyl resorcinarenes in the gas phase

The noncovalent complexation of tetraethyl and tetraphenyl resorcinarenes with mono-, di-, and oligosaccharides was studied with negative-polarization electrospray ionization quadrupole ion trap and electrospray ionization Fourier-transform ion cyclotron resonance mass-spectrometric analysis. The saccharides formed 1:1 complexes with deprotonated resorcinarenes, which exhibited clear size and structure selectivity in their complexation. In the case of the monosaccharides, hexoses formed much more abundant and kinetically stable complexes than pentoses or deoxyhexoses. A comparison of the mono-, di-, and oligosaccharides revealed that both the relative abundance and stability of the complexes increase up to biose and triose, but start to decrease after that point, as the length of the oligosaccharide is increased. This behavior was rationalized by comparing the lowest-energy conformations of the complexes formed between the resorcinarene and oligosaccharides. This comparison was achieved by using theoretical calculations and X-ray crystal studies.     

Furanose dynamics in the HhaI methyltransferase target DNA studied by solution and solid-state NMR relaxation

Both solid-state and solution NMR relaxation measurements are routinely used to quantify the internal dynamics of biomolecules, but in very few cases have these two techniques been applied to the same system, and even fewer attempts have been made so far to describe the results obtained through these two methods through a common theoretical framework. We have previously collected both solution 13C and solid-state 2H relaxation measurements for multiple nuclei within the furanose rings of several nucleotides of the DNA sequence recognized by HhaI methyltransferase. The data demonstrated that the furanose rings within the GCGC recognition sequence are very flexible, with the furanose rings of the cytidine, which is the methylation target, experiencing the most extensive motions. To interpret these experimental results quantitatively, we have developed a dynamic model of furanose rings based on the analysis of solid-state 2H line shapes. The motions are modeled by treating bond reorientations as Brownian excursions within a restoring potential. By applying this model, we are able to reproduce the rates of 2H spin-lattice relaxation in the solid and 13C spin-lattice relaxation in solution using comparable restoring force constants and internal diffusion coefficients. As expected, the 13C relaxation rates in solution are less sensitive to motions that are slower than overall molecular tumbling than to the details of global molecular reorientation, but are somewhat more sensitive to motions in the immediate region of the Larmor frequency. Thus, we conclude that the local internal motions of this DNA oligomer in solution and in the hydrated solid state are virtually the same, and we validate an approach to the conjoint analysis of solution and solid-state NMR relaxation and line shapes data, with wide applicability to many biophysical problems.     

Cooperative assistance in bifunctional organocatalysis: enantioselective mannich reactions with aliphatic and aromatic imines

Hold them tight: Guided by X-ray structures, bifunctional thiourea catalysts containing an activating intramolecular hydrogen bond were redesigned. The new catalysts were used to effect a highly enantioselective Mannich reaction between malonates and both aliphatic and aromatic imines (see scheme; Boc=tert-butoxycarbonyl).