Anti Conformation Research Articles

London Dispersion Favors Sterically Hindered Diarylthiourea Conformers in Solution

AbstractWe present an experimental and computational study on the conformers of N,N′‐diphenylthiourea substituted with different dispersion energy donor (DED) groups. While the unfolded anti–anti conformer is the most relevant for thiourea catalysis, intramolecular noncovalent interactions counterintuitively favor the folded syn–syn conformer, as evident from a combination of low‐temperature nuclear magnetic resonance measurements and computations. In order to quantify the noncovalent interactions, we utilized local energy decomposition analysis and symmetry‐adapted perturbation theory at the DLPNO‐CCSD(T)/def2‐TZVPP and sSAPT0/6‐311G(d,p) levels of theory. Additionally, we applied a double‐mutant cycle to experimentally study the effects of bulky substituents on the equilibria. We determined London dispersion as the key interaction that shifts the equilibria towards the syn–syn conformers. This preference is likely a factor why such thiourea derivatives can be poor catalysts.

The 2'-deoxyribofuranoside of 3-phenyltetrahydropyrimido[4,5-c]pyridazin-7-one: a bicyclic nucleoside with sugar residues in N and S conformations, and its molecular recognition.

The title compound 3-phenyltetrahydropyrimido[4,5-c]pyridazine 2'-deoxyribonucleoside [systematic name: 6-(2-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-3-phenylpyrimido[4,5-c]pyridazin-7-one monohydrate, C17H18N4O4·H2O, 1] shows two conformations in the crystalline state and the two conformers (1a and 1b) adopt different sugar puckers. The sugar residue of 1a shows a C2'-endo S-type conformation, while 1b displays a C3'-endo N-type sugar pucker. Both conformers adopt similar anti conformations around the N-glycosylic bonds, with χ= -97.5 (3)° for conformer 1a and χ= -103.8 (3)° for conformer 1b. The extended crystalline network is stabilized by several intermolecular hydrogen bonds involving nucleoside and water molecules. The nucleobases and phenyl substituents of the two conformers (1a and 1b) are stacked and display a reverse alignment. A Hirshfeld surface analysis supports the hydrogen-bonding pattern, while curvedness surfaces visualize the stacking interactions of neighbouring molecules. The recognition face of nucleoside 1 for base-pair formation mimics that of 2'-deoxythymidine. Nucleoside 1 shows two pKa values: 1.8 for protonation and 11.2 for deprotonation. DNA oligonucleotides containing nucleoside 1 were synthesized and hybridized with complementary DNA strands. Nucleoside 1 forms a stable base pair with dA which is as stable as the canonical dA-dT pair. The bidentate 1-dA base pair is strengthened by a third hydrogen bond provided by the dA analogue 3-bromopyrazolo[3,4-d]pyrimidine-4,6-diamine 2'-deoxyribofuranoside (4). By this, duplex stability is increased and the suggested base-pairing patterns are supported.

Single-Color Isomer-Resolved Spectroscopy.

Structural isomers, such as conformers or tautomers, are of significant importance across chemistry and biology, as they can have different functionalities. In gas-phase experiments using molecular beams, formation of many different isomers cannot be prevented, and their presence significantly complicates the assignment of spectral lines. Current isomer-resolved spectroscopic techniques heavily rely on theoretical calculations or make use of elaborate double-resonance schemes. We show here that isomer-resolved spectroscopy can also be performed using a single tunable laser. In particular, we demonstrate single-color isomer-resolved spectroscopy by utilizing electrostatic deflection to spatially separate the isomers. We show that for 3-aminophenol we can spatially separate the syn and anti conformers and use these pure samples to perform high-resolution REMPI spectroscopy, making the assignment of transitions to a particular isomer trivial, without any additional a priori information. This approach allows one to add isomer specificity to any molecular-beam-based experiment.

Novel eGZ-motif formed by regularly extruded guanine bases in a left-handed Z-DNA helix as a major motif behind CGG trinucleotide repeats.

The expansion of d(CGG) trinucleotide repeats (TRs) lies behind several important neurodegenerative diseases. Atypical DNA secondary structures have been shown to trigger TR expansion: their characterization is important for a molecular understanding of TR disease. CD spectroscopy experiments in the last decade have unequivocally demonstrated that CGG runs adopt a left-handed Z-DNA conformation, whose features remain uncertain because it entails accommodating GG mismatches. In order to find this missing motif, we have carried out molecular dynamics (MD) simulations to explore all the possible Z-DNA helices that potentially form after the transition from B- to Z-DNA. Such helices combine either CpG or GpC Watson-Crick steps in Z-DNA form with GG-mismatch conformations set as either intrahelical or extrahelical; and participating in BZ or ZZ junctions or in alternately extruded conformations. Characterization of the stability and structural features (especially overall left-handedness, higher-temperature and steered MD simulations) identified two novel Z-DNA helices: the most stable one displays alternately extruded Gs, and is followed by a helix with symmetrically extruded ZZ junctions. The G-extrusion favors a seamless stacking of the Watson-Crick base pairs; extruded Gs favor syn conformations and display hydrogen-bonding and stacking interactions. Such conformations could have the potential to hijack the MMR complex, thus triggering further expansion.

Aggregation-Induced Emission with Alkynylcoumarin Dinuclear Gold(I) Complexes: Photophysical, Dynamic Light Scattering, and Time-Dependent Density Functional Theory Studies.

Aggregation-induced emission (AIE) has gained a remarkable amount of interest in the past 20 years, but the majority of the studies are based on organic structures. Herein, three dinuclear gold(I) complexes, with the general formula [PPh2XPPh2-Au2-Coum2], where the Au(I) atom is linked to three different diphosphanes [PPh2XPPh2; DPPM for X = CH2 (1.1), DPPP for X = (CH2)3 (1.2), and DPPA for X = C≡C (1.3)] and the propynyloxycoumarin precursor (1, 4-methyl-substituted coumarin), have been synthesized. The compounds present AIE characteristics, AIEgens, with high luminescence quantum yields in the solid state when they are compared to dilute solutions. Photophysical studies (steady-state and time-resolved fluorescence) were obtained, with AIE being observed with the three gold(I) complexes in acetonitrile/water mixtures. This was further corroborated with dynamic light scattering measurements. Time-dependent density functional theory (TDDFT) electronic calculations show that the compounds have different syn and anti conformations (relative to the coumarin core) with 1.1 syn and 1.2 and 1.3 both anti. From time-resolved fluorescence experiments, the augment in the contribution of the longer decay component is found to be associated with the emission of the aggregate (AIE effect) and its nature (involving a dimer) rationalized from TDDFT electronic calculations.

Interaction Mechanisms and Interface Configuration of Cysteine Adsorbed on Gold, Silver, and Copper Nanoparticles.

Cysteine-protected metal nanoparticles (NPs) have shown interesting physicochemical properties of potential utility in biomedical applications and in the understanding of protein folding. Herein, cysteine interaction with gold, silver, and copper NPs is characterized by Raman spectroscopy and density functional theory calculations to elucidate the molecular conformation and adsorption sites for each metal. The experimental analysis of Raman spectra upon adsorption with respect to free cysteine indicates that while the C-S bond and carboxyl group are similarly affected by adsorption on the three metal NPs, the amino group is sterically influenced by the electronegativity of each metal, causing a greater modification in the case of gold NPs. A theoretical approach that takes into consideration intermolecular interactions using two cysteine molecules is proposed using a S-metal-S interface motif anchored to the metal surface. These interactions generate the stabilization of an organo-metallic complex that combines gauche (PH) and anti (PC) rotameric conformers of cysteine on the surface of all three metals. Similarities between the calculated Raman spectra and experimental data confirm the thiol and carboxyl as adsorption groups for gold, silver, and copper NPs and suggest the formation of monomeric "staple motifs" that have been found in the protecting monolayer of atomic-precise thiolate-capped metal nanoclusters.

NMR evidence for hydrogen bonding stabilized anti conformation of 1-methoxy-1-methyl-3-phenylurea and the concentration detection by SERS

Phenylurea-based herbicides have been widely used to control the plant growth. Due to their toxicity, strict regulations to limit their usage have been applied. Developing trace detection protocols of substituted phenylureas has attracted more attention, especially with the availability of a wide range of spectroscopic and analytical techniques. In this study, the conformational and structural properties of 1-methoxy-1-methyl-3-phenylurea (MMPU) which belongs to the family of phenylurea-based herbicides have been characterized. The anti-configuration, facilitated by the intramolecular hydrogen bonding between the oxygen atom of the methoxy moiety and the acidic amide proton, was observed using the nuclear magnetic resonance (NMR) spectroscopy through the Selective Nuclear Overhauser Effect (SelNOE) approach. The density functional theory (DFT) calculations suggested that the anti form is at least 9 kcal/mol more stable than the corresponding syn structure. Possible degradation pathways of such a class of herbicides can be explored when a firm understanding of their electronic and conformational behaviors is established. The detection of trace MMPU has been successfully developed using the surface-enhanced Raman scattering (SERS) spectroscopic tool. The most enhanced peak associated with the carbonyl group stretching vibration which appears nearly at 1600 cm−1 has presented a Raman enhancement factor of 3.24 × 105 and a micrommolar limit of detection.

Spectroscopic and theoretical studies of some 2-(2′-ethylsulfanyl)acetyl-5-substituted furans and thiophenes

The conformational equilibrium of 2-(2′-ethylsulfanyl)acetyl-5-substituted furans and thiophenes [EtSCH2C(O)(C4H2X)Y] (1–5; Scheme 1) was determined through the infrared analysis of the carbonyl stretching band (νCO) supported by DFT (B3LYP/aug-cc-pVTZ) and molecular dynamics simulations (OPLS-AA). Six stable conformations, syn(1–3) and anti(1–3), were obtained through the optimisation of the isolated systems, where the syn/anti nomenclature refers to the dihedral angle between the carbonyl and the aromatic heteroatom (O=C–C–X; X = O, S) and 1, 2, and 3 refer to the ethyl rotation (Scheme 2) (torsion around the γ dihedral angle). The three ethyl conformers resemble six- (1 and 2) or seven-(3) member pseudo-rings with an electrostatic intramolecular hydrogen bond (Oδ-···Hδ+). The IR spectra in solution show νCO doublets for all compounds in all solvents (n-C6H14, CCl4, CHCl3, CH2Cl2 and CH3CN). The polarisable continuum model and molecular dynamics data allow the lowest wavenumber and more intense νCO IR component to be ascribed to the three anti conformers of the furan derivatives and to the three syn ones of the thiophene compounds. The conformational preferences of all compounds are governed by a balance between orbital and coulombic interactions, as estimated by means of natural bond orbital, natural coulomb electrostatic, pairwise steric exchange energy, quantum theory of atoms in molecules, non-covalent interaction and short-contact analyses. While the conformational isomerism of the ethylthioacetyl moiety is determined by both quantum and columbic effects, the equilibrium involving the carbonyl and heterocyclic moiety is controlled largely by electrostatic interactions.

Splitting the Ring: Impact of Ortho and Meta Pi Conjugation Pathways through Disjointed [8]Cycloparaphenylene Electronic Materials.

In this report, we describe the synthesis and electronic properties of small-molecule and polymeric [8]cycloparaphenylenes ([8]CPPs) with disjointed pi-conjugated substituents. Arylene-ethynylene linkers were installed on opposite sides of the [8]CPP nanohoop as separated by three phenyl units on either side such that the monomer systems have syn (C2 symmetry) and anti (C1 symmetry) conformers with a small energy gap (0.1-0.6 kcal/mol). This disjoined substitution pattern necessarily forces delocalization through and around the CPP radial structure. We demonstrate new electronic states from this radial/linear mixing in both the small molecules and the pi extended polymers. Quantum chemical calculations reveal that these electronic processes arise from multiple operative radial/linear conjugation pathways, as the disjoint pattern results in both ortho and meta connections to the CPP ring. These results affirm the unique nature of hybrid radial and linear pi electron delocalization operative in these new conjugation pathways.

Effects of N7-Alkylguanine Conformation and Metal Cofactors on the Translesion Synthesis by Human DNA Polymerase η.

Non-enzymatic alkylation on DNA often generates N7-alkyl-2'-deoxyguanosine (N7alkylG) adducts as major lesions. N7alkylG adducts significantly block replicative DNA polymerases and can be bypassed by translesion synthesis (TLS) polymerases such as polymerase η (polη). To gain insights into the bypass of N7alkylG by TLS polymerases, we conducted kinetic and structural studies of polη catalyzing across N7BnG, a genotoxic lesion generated by the carcinogenic N-nitrosobenzylmethylamine. The presence of templating N7BnG in the polη catalytic site decreased the replication fidelity by ∼9-fold, highlighting the promutagenicity of N7BnG. The catalytic efficiency for dCTP incorporation opposite N7BnG decreased ∼22-fold and ∼7-fold compared to the incorporation opposite undamaged guanine in the presence of Mg2+ and Mn2+, respectively. A crystal structure of the complexes grown with polη, templating N7BnG, incoming dCTP, and Mg2+ ions showed the lack of the incoming nucleotide and metal cofactors in the polη catalytic site. Interestingly, the templating N7BnG adopted a syn conformation, which has not been observed in the published N7alkylG structures. The preferential formation of syn-N7BnG conformation at the templating site may deter the binding of an incoming dCTP, causing the inefficient bypass by polη. In contrast, the use of Mn2+ in place of Mg2+ in co-crystallization yielded a ternary complex displaying an anti-N7BnG:dCTP base pair and catalytic metal ions, which would be a close mimic of a catalytically competent state. We conclude that certain bulky N7-alkylG lesions can slow TLS polymerase-mediated bypass by adopting a catalytically unfavorable syn conformation in the replicating base pair site.

7,8-Dihydro-8-oxo-1,N6-ethenoadenine: an exclusively Hoogsteen-paired thymine mimic in DNA that induces A→T transversions in Escherichia coli.

This work investigated the structural and biological properties of DNA containing 7,8-dihydro-8-oxo-1,N6-ethenoadenine (oxo-ϵA), a non-natural synthetic base that combines structural features of two naturally occurring DNA lesions (7,8-dihydro-8-oxoadenine and 1,N6-ethenoadenine). UV-, CD-, NMR spectroscopies and molecular modeling of DNA duplexes revealed that oxo-ϵA adopts the non-canonical syn conformation (χ = 65º) and fits very well among surrounding residues without inducing major distortions in local helical architecture. The adduct remarkably mimics the natural base thymine. When considered as an adenine-derived DNA lesion, oxo-ϵA was >99% mutagenic in living cells, causing predominantly A→T transversion mutations in Escherichia coli. The adduct in a single-stranded vector was not repaired by base excision repair enzymes (MutM and MutY glycosylases) or the AlkB dioxygenase and did not detectably affect the efficacy of DNA replication in vivo. When the biological and structural data are viewed together, it is likely that the nearly exclusive syn conformation and thymine mimicry of oxo-ϵA defines the selectivity of base pairing in vitro and in vivo, resulting in lesion pairing with A during replication. The base pairing properties of oxo-ϵA, its strong fluorescence and its invisibility to enzymatic repair systems in vivo are features that are sought in novel DNA-based probes and modulators of gene expression.

Rotational spectrum of anti- and gauche-4-cyano-1-butyne (C5H5N) – An open-chain isomer of pyridine

The analysis of the rotational spectrum of 4-cyano-1-butyne, an open-chain isomer of pyridine, is presented herein for the first time. Transitions for the ground vibrational states of both conformational isomers, anti and gauche, were observed in the 8–38 GHz and 130–360 GHz frequency ranges and fit to effective sextic distorted-rotor Hamiltonians with low uncertainty (σfit < 50 kHz), allowing for their potential detection by radioastronomy or in harsh reaction environments. The microwave region includes hyperfine-split transitions for both conformers, allowing for the experimental determination of the χaa, χbb, and χcc quadrupole coupling constants. In the millimeter-wave region, not every observable ground-state transition could be satisfactorily addressed by a single-state Hamiltonian due to Coriolis coupling with the low-energy vibrationally excited states. Thus, effective single-state fits of the ground states were obtained by including only Ka-series transitions without obviously perturbed energy levels. Importantly, the effective fit does include the most intense transitions throughout the observed frequency ranges. The predicted values (MP2/cc-pVTZ) are in close agreement with the experimental spectroscopic constants. These data provide a sufficient foundation for the identification of anti- and gauche-4-cyano-1-butyne in the interstellar medium by radioastronomy. The gauche conformer is estimated to lie 1.00 (5) kcal/mol higher in energy than the anti conformer, as determined using experimental transition intensities.

8-Furylimidazolo-2'-deoxycytidine: crystal structure, packing, atropisomerism and fluorescence.

8-Furylimidazolo-2'-deoxycytidine (furImidC), C14H14N4O5, is a fluorescent analogue of 2'-deoxycytidine, also displaying the same recognition face. As a constituent of DNA, furImidC forms extraordinarily strong silver-mediated self-pairs. Crystal structure determination revealed that furImidC adopts two types of disordered residues: the sugar unit and the furyl moiety. The disorder of the sugar residue amounts to an 87:13 split. The disorder of the furyl ring results from axial chirality at the C8-C2'' bond connecting the nucleobase to the heterocycle. The two atropisomers are present in unequal proportions [occupancies of 0.69 (2) and 0.31 (2)], and the nucleobase and the furyl moiety are coplanar. Considering the atomic sites with predominant occupancy, an anti conformation with χ= - 147.2 (7)° was found at the glycosylic bond and the 2'-deoxyribosyl moiety shows a C2'-endo (S, 2T1) conformation, with P= 160.0°. A 1H NMR-based conformational analysis of the furanose puckering revealed that the S conformation predominates also in solution. In the solid state, two neighbouring furImidC molecules are arranged in a head-to-tail fashion, but with a notable tilt of the molecules with respect to each other. Consequently, one N-H...N hydrogen bond is found for neighbouring molecules within one layer, while a second N-H...N hydrogen bond is formed to a molecule of an adjacent layer. In addition, hydrogen bonding is observed between the nucleobase and the sugar residue. A Hirshfeld surface analysis was performed to visualize the intermolecular interactions observed in the X-ray study. In addition, the fluorescence spectra of furImidC were measured in solvents of different polarity and viscosity. furImidC responds to microenvironmental changes (polarity and viscosity), which is explained by a hindered rotation of the furyl residue in solvents of high viscosity.

A Chimeric DNA/RNA Antiparallel Quadruplex with Improved Stability.

Nucleic acid quadruplexes are proposed to play a role in the regulation of gene expression, are often present in aptamers selected for specific binding functions and have potential applications in medicine and biotechnology. Therefore, understanding their structure and thermodynamic properties and designing highly stable quadruplexes is desirable for a variety of applications. Here, we evaluate DNA→RNA substitutions in the context of a monomolecular, antiparallel quadruplex, the thrombin‐binding aptamer (TBA, GGTTGGTGTGGTTGG) in the presence of either K+ or Sr2+. TBA predominantly folds into a chair‐type configuration containing two G‐tetrads, with G residues in both syn and anti conformation. All chimeras with DNA→RNA substitutions (G→g) at G residues requiring the syn conformation demonstrated strong destabilization. In contrast, G→g substitutions at Gs with anti conformation increased stability without affecting the monomolecular chair‐type topology. None of the DNA→RNA substitutions in loop positions affected the quadruplex topology; however, these substitutions varied widely in their stabilizing or destabilizing effects in an unpredictable manner. This analysis allowed us to design a chimeric DNA/RNA TBA construct that demonstrated substantially improved stability relative to the all‐DNA construct. These results have implications for a variety of quadruplex‐based applications including for the design of dynamic nanomachines.

Theoretical and X-Ray Evidence of Electrostatic Phosphonium anti and gauche Effects.

Sulphur, not phosphorus, is the only known third-row element capable of experiencing an electrostatic gauche effect with fluorine. Some six-membered rings containing an endocyclic phosphorus atom and a β-fluorine substituent that can interconvert to axial (gauche relative to phosphorus) and equatorial positions were then analysed. While phosphines do not establish an electrostatic attraction between fluorine and phosphorus, some oxidised forms exhibit surprising stability for the sterically disfavoured axial orientation. Because the nature of this behaviour was not obvious, since an intramolecular hydrogen bond can appear, a phosphonium derivative was further studied and its axial conformation was found to be highly stable. A preference for the gauche arrangement appears even for the acyclic and sterically hindered (2-fluoroethyl)triphenylphosphonium cation. On the other hand, (ethane-1,2-diyl)bis(phosphonium) cations are exclusively in anti conformation due to an (+/+)-electrostatic repulsion between the positively charged phosphonium groups.

Atropisomeric Conjugated Diimides: A Class of Thermally Responsive Organic Semiconductors

Atropisomerism has been studied in many research fields; however, it is rarely studied in organic semiconductors. In this work, we report a series of room-temperature-stable atropisomeric conjugated diimides, Syn-NDI and Anti-NDI based on 1,4,5,8-naphthalenetetracarboxylic diimides (NDIs) as well as Syn-PDI and Anti-PDI based on 3,4:9,10-perylenetetracarboxylic diimides (PDIs). For these two pairs of atropisomers, the Syn and Anti conformers can be interconverted when they are in heated solution, whereas in the solid state, only the Syn conformers can converted to Anti conformers when thermally annealed. This feature can be applied to realize thermally responsive organic field-effect transistors (OFETs). Remarkably, when thermally annealed at a certain temperature, the Syn atropisomers can be fast converted to their respective Anti ones, and OFETs originally based on the Syn semiconductors show a dramatic improvement in electron mobility. For OFETs originally based on Syn-NDI, a 100-fold improvement in electron mobility is recorded when Syn-NDI was converted to Anti-NDI, while for OFETs originally based on Syn-PDI, a 5000-fold improvement in electron mobility is recorded when Syn-PDI was converted to Anti-PDI. In contrast, thermal annealing is found to have a negligible effect for OFETs based on Anti semiconductors, with the electron mobility on the same order of magnitude for all Anti semiconductor devices. This is the first time that the atropisomerism has been exploited in organic semiconductors, demonstrating great potential for stimuli-responsive devices.

Ferrocene Rotary Switches Featuring 2‐Pyridyl‐1,2,3‐triazole “Click” Chelates

AbstractThree ferrocene‐based rotary switches featuring 2‐pyridyl‐1,2,3‐triazole (pytri) “click” chelates have been developed. The rotors can be switched from a folded (syn) to extended (anti) conformation by the addition of [Cu(CH3CN)4](PF6) and 6,6′‐dimesityl‐2,2′‐bipyridine. This extension process could be reversed by the addition of 1,4,8,11‐tetraazacyclotetradecane (cyclam) to sequester the Cu(I) ions. Disappointingly, the weakness of the pytri chelates prevented the development of an electrochemically switchable system.

Nuclear Magnetic Resonance Spectra and AMBER OL3 and ROC-RNA Simulations of UCUCGU Reveal Force Field Strengths and Weaknesses for Single-Stranded RNA.

Single-stranded regions of RNA are important for folding of sequences into 3D structures and for design of therapeutics targeting RNA. Prediction of ensembles of 3D structures for single-stranded regions often involves classical mechanical approximations of interactions defined by quantum mechanical calculations on small model systems. Nuclear magnetic resonance (NMR) spectra and molecular dynamics (MD) simulations of short single strands provide tests for how well the approximations model many of the interactions. Here, the NMR spectra for UCUCGU at 2, 15, and 30 °C are compared to simulations with the AMBER force fields, OL3 and ROC-RNA. This is the first such comparison to an oligoribonucleotide containing an internal guanosine nucleotide (G). G is particularly interesting because of its many H-bonding groups, large dipole moment, and proclivity for both syn and anti conformations. Results reveal formation of a G amino to phosphate non-bridging oxygen H-bond. The results also demonstrate dramatic differences in details of the predicted structures. The variations emphasize the dependence of predictions on individual parameters and their balance with the rest of the force field. The NMR data can serve as a benchmark for future force fields.

Mechanistic insights into multiple-step transport of mitochondrial ADP/ATP carrier

The ADP/ATP carrier (AAC) is crucial for mitochondrial functions by importing ADP and exporting ATP across the inner mitochondrial membrane. However, the mechanism of highly specific ADP recognition and transport by AAC remains largely elusive. In this work, spontaneous ADP binding process to the ground c-state AAC was investigated through rigorous molecular dynamics simulations of over 31 microseconds in total. With improved simulation strategy, we have successfully identified a highly specific ADP binding site in the upper region of the cavity, and this site exhibits selectivity for ADP over ATP based on free-energy calculations. Sequence analyses on adenine nucleotide transporters also suggest that this subgroup uses the upper region of the cavity, rather than the previously proposed central binding site located at the bottom of the cavity to discriminate their substrates. Identification of the new site unveils the unusually high substrate specificity of AAC and explains the dependence of transport on the flexibility between anti and syn glycosidic conformers of ADP. Moreover, this new site together with the central site supports early biochemical findings. In light of these early findings, our simulations described a multi-step model in which the carrier uses different sites for substrate attraction, recognition and conformational transition. These results provide new insights into the transport mechanism of AAC and other adenine nucleotide transporters.

Noncovalent wedging effect catalyzed the cis to syn transformation of a surface-adsorbed polymer backbone toward an unusual thermodynamically stable supramolecular product.

The significant influence of noncovalent interactions on catalytic processes has been recently appreciated but is still in its infancy. In this report, it is found that wedging Me-PTCDI (small-molecule) between the alkyl chains of PffBT4T-2OD (polymer) and a graphite substrate can reduce the energy barrier of flipping over the surface-adsorbed alkylthiophene group from the cis to syn conformation, revealing the catalytic role of Me-PTCDI via a noncovalent wedging effect. The wedging of Me-PTCDI brings the interactions between the alkyl chains and substrate to a very weak level by lifting up the alkyl chains, which eliminates the major hindrance of the flipping process to one main factor: the torsion of the dihedral angles of the thiophene group. The Me-PTCDI/syn PffBT4T-2OD arrangement shows unusual stability compared to the cis one because the syn conformation allows the alkyl chains to construct dense lamella and facilitates interactions between Me-PTCDI and the syn PffBT4T-2OD backbones. The results are helpful for boosting the development of noncovalent catalysis and bottom-up fabrications toward devices functionalized at a molecular level.