DNA hybridization kinetics: zippering, internal displacement and sequence dependence

Although the thermodynamics of DNA hybridization is generally well established, the kinetics of this classic transition is less well understood. Providing such understanding has new urgency because DNA nanotechnology often depends critically on binding rates. Here, we explore DNA oligomer hybridization kinetics using a coarse-grained model. Strand association proceeds through a complex set of intermediate states, with successful binding events initiated by a few metastable base-pairing interactions, followed by zippering of the remaining bonds. But despite reasonably strong interstrand interactions, initial contacts frequently dissociate because typical configurations in which they form differ from typical states of similar enthalpy in the double-stranded equilibrium ensemble. Initial contacts must be stabilized by two or three base pairs before full zippering is likely, resulting in negative effective activation enthalpies. Non-Arrhenius behavior arises because the number of base pairs required for nucleation increases with temperature. In addition, we observe two alternative pathways—pseudoknot and inchworm internal displacement—through which misaligned duplexes can rearrange to form duplexes. These pathways accelerate hybridization. Our results explain why experimentally observed association rates of GC-rich oligomers are higher than rates of AT- rich equivalents, and more generally demonstrate how association rates can be modulated by sequence choice

mRNA Secondary Structures Fold Sequentially But Exchange Rapidly In Vivo

Self-cleavage assays of RNA folding reveal that mRNA structures fold sequentially in vitro and in vivo, but exchange between adjacent structures is much faster in vivo than it is in vitro

Analysis of In-Vivo LacR-Mediated Gene Repression Based on the Mechanics of DNA Looping

Interactions of E. coli lac repressor (LacR) with a pair of operator sites on the same DNA molecule can lead to the formation of looped nucleoprotein complexes both in vitro and in vivo. As a major paradigm for loop-mediated gene regulation, parameters such as operator affinity and spacing, repressor concentration, and DNA bending induced by specific or non-specific DNA-binding proteins (e.g., HU), have been examined extensively. However, a complete and rigorous model that integrates all of these aspects in a systematic and quantitative treatment of experimental data has not been available. Applying our recent statistical-mechanical theory for DNA looping, we calculated repression as a function of operator spacing (58–156 bp) from first principles and obtained excellent agreement with independent sets of in-vivo data. The results suggest that a linear extended, as opposed to a closed v-shaped, LacR conformation is the dominant form of the tetramer in vivo. Moreover, loop-mediated repression in wild-type E. coli strains is facilitated by decreased DNA rigidity and high levels of flexibility in the LacR tetramer. In contrast, repression data for strains lacking HU gave a near-normal value of the DNA persistence length. These findings underscore the importance of both protein conformation and elasticity in the formation of small DNA loops widely observed in vivo, and demonstrate the utility of quantitatively analyzing gene regulation based on the mechanics of nucleoprotein complexes

Reactions of the Pd-Sn metal pair

The reaction of the Pd(0) complexes (R-2'PC2H4PR2')Pd(C2H4) (R' = Pr-1, Bu-t) and ((Pr3P)-Pr-1)(2)Pd with SnR2 (R e.g. CH(SiMe3)(2)), Sn2Me6, and R3SnH (R = Me, Bu-n) has been studied, the latter representing tin in its oxidation states II-IV. Thereby, information was obtained on the mechanisms of four Pd-catalyzed reactions of organotin compounds, i.e., (a) the (2+2+1) cycloaddition of 2 ethyne and 1 stannylene to form a stannole, (b) the hydrogen elimination from trialkylstannanes to give hexaalkyldistannanes, (c) the hydrostannation of alkynes to afford vinylstannanes, and (d) the jive of alkynes to yield distannylalkenes. All reactions are likely to involve intermediates having Pd-Sn bonds, although for (d) the occurrence of a previously suggested L2Pd(SnMe3)(2) intermediate in the catalytic cycle has en ruled out

Zur Lewis-Acidität von Nickel(0), VI Dimethylmethylenoxosulfuran-Komplexe von Nickel(0)

Aus Tris(ethen)nickel(0) und Dimethylmethylenoxosulfuran, Me2-(O)SCH2, entsteht in Ether unterhalb 0°C {Me2(O)SCH2}-Ni(C2H4)2 (1). Bei 0°C zersetzt sich 1 explosionsartig unter Freisetzung von Ethen, Cyclopropan und Methan. Umsetzung von 1 mit CO bei −78°C führt zu {Me2(O)SCH2}Ni(CO)3 (2), das bis 20°C stabil ist. Die Methylensulfuran-Komplexe wurden durch ihre IR- und NMR-Spektren charakterisiert

Mono- and bis(ethyne)nickel(0) complexes

Various (ligand)nickel(0)-ethene complexes react with ethyne in ether or pentane at low temperature to afford crystalline compounds of types (R3P)2Ni(C2H2), {(RO)3P}2Ni(C2H2), (tBuNC)2Ni(C2H2), (R3P)Ni(C2H2)(C2H4), {(R3P)-Ni(C2H4)}2(µ-C2H2), {(R3P)Ni(C2H2)}2(µ-C2H2), and (R3P)Ni(C2H2)2 (R = Me, Et, iPr,Ch, Ph). The chemical and spectroscopic properties of the new complexes are reported

Coupling of Two Ethyne Molecules at a Nickel Center to Form a Nickelacyclopentadiene Complex

The Ni-catalyzed cyclooligomerization of acetylene according to Reppeprobably proceeds stepwise via a nickelacyclopentadiene intermediate. By reaction of 1 with ethyne in excess and iPr2PCH2CH2PiPr2 in pentane at −78°C (!) it has now been possible for the first time to obtain a NiC4H4-complex via 2 and to characterize it IR and NMR spectroscopically. In the formula of 2 on the right a Ni(iPr2PCH2CH2PiPr2) unit has been omitted

Organonickel(IV) Chemistry: A New Catalyst?

With scorpionate ligands finding their way into organonickel chemistry, the state of the art of present-day nickel(IV) chemistry is highlighted. Will rapid CX coupling reactions emerge as a domain of higher-oxidation-state nickel chemistry

Bis(dimethylphosphino)methan-Nickel(0)-Komplexe

The reaction of tris(ethene)nickel(0) with stoichiometric amounts of bis(dimethylphosphino)methane (dmpm) in ether at low temperature affords the yellow crystalline, dinuclear complexes (dmpm)Ni2(CH4)4 (1) and (dmpm)2Ni2(C2H4)2 (2). 2 reacts with ethyne to yield (dmpm)2Ni2(C2H2)2 (3). When 2 is treated with CO at —40 °C the primary product is (dmpm)2Ni2(CO)2(µ-CO) (4). At 20 °C 4 is converted by additional CO into (dmpm)2Ni2(CO)4 (5), which has already been characterized as the reaction product of Ni(CO)4 with dmpm. In compounds 1—5 the bidentate dmpm acts as a bridging and not as a chelating ligand. The structures of complexes 1—4 were assigned on the basis of their 13C and 31P NMR spectra