Conformational Analysis of C-Disaccharides using Molecular Mechanics Calculations

ABSTRACT

Relaxed-residue energy maps based on the MM3 force field were computed for the methyl glycosides of eight C-linked D-glucosyl disaccharides: the two-bond axial-equatorial linked disaccharides β-kojibioside [(1→2)α–], β-nigeroside [(1→3)α–] and β-maltose [(1→4)α–], the two-bond equatorial-equatorial linked disaccharides β-sophoroside [(1→2)β–], β–laminarabioside [(1→3)β-], β–cellobioside [(1→4)β–] and the three-bond-linked (1→6) disacharides C-isomaltoside and C-gentiobioside. Optimized structures were calculated on a 20° grid spacing of the torsional angles about the C-glycosidic bonds and the final isoenergy surfaces were based on 11664 conformations, for the two-bond-linked disaccharides and 69984 conformations for the three-bond-linked disaccharides. Boltzmann-weighted ³J coupling constants were calculated and compared to the experimental values. They are satisfactory except for maltose where hydrogen bonds cause an over-estimation of the energy differences between the conformers. The energy maps are similar to maps of the corresponding O-disaccharides, but there are differences in the locations and the relative energies of the minima. The preferred conformations of the C-glycosidic bonds are as if they were conforming to the exo-anomeric effect but are closer to staggered conformations than shown by the MM3 results for the O-linkages.     

Enthalpy–Entropy Compensation Combined with Cohesive Free‐Energy Densities for Tuning the Melting Temperatures of Cyanobiphenyl Derivatives

This work illustrates how minor structural perturbations produced by methylation of 4′‐(dodecyloxy)‐4‐cyanobiphenyl leads to enthalpy–entropy compensation for their melting processes, a trend which can be analyzed within the frame of a simple intermolecular cohesive model. The transformation of the melting thermodynamic parameters collected at variable temperatures into cohesive free‐energy densities expressed at a common reference temperature results in a novel linear correlation, from which melting temperatures can be simply predicted from molecular volumes.     

Diastereo‐ and Enantioselective Synthesis of Organometallic Bis(helicene)s by a Combination of C?H Activation and Dynamic Isomerization

Homochiral and heterochiral cis‐bis‐cycloplatinated‐[6]helicene derivatives 1 b^{1, 2} , as representative examples of platina[6]helicenes that share a common platinum center, have been prepared. A diastereo‐ and enantioselective synthesis, which combines CH activation and dynamic isomerization from heterochiral structure 1 b² into homochiral structure 1 b¹ , is also described. Overall, this isomerization process results in the transfer of chiral information from one helicene moiety to the other one. The chiroptical properties of homochiral (P)‐ and (M)‐ 1 b¹ were greatly modified upon oxidation into their corresponding (P)‐ and (M)‐diiodo‐Pt^IV complexes ( 5 ). The changes were also analyzed by performing theoretical calculations. C? H activation in the synthesis of organometallic helicenes is further demonstrated by the preparation of cis‐bis‐cycloplatinated‐[8]helicene 1 c .     

Mixed Oligoureas Based on Constrained Bicyclic and Acyclic β‐Amino Acids Derivatives: On the Significance of the Subunit Configuration for Folding

The combination of a non‐functionalized constrained bicyclo[2.2.2]octane motif along with urea linkages allowed the formation of a highly rigid 2.5_12/14 helical system both in solution and the solid state. In this work, we aimed at developing stable and functionalized systems as promising materials for biological applications in investigating the impact of this constrained motif and its configuration on homo and heterochiral mixed‐oligourea helix formation. Di‐, tetra‐, hexa‐, and octa‐oligoureas alternating the highly constrained bicyclic motif of (R) or (S) configuration with acyclic (S)‐β³‐amino acid derivatives were constructed. Circular dichroism (CD), NMR experiments, and the X‐ray crystal structure of the octamer unequivocally proved that the alternating heterochiral R/S sequences form a stable left‐handed 2.5‐helix in contrast to the mixed (S/S)‐oligoureas, which did not adopt any defined secondary structure. We observed that the (?)‐synclinal conformation around the C_α? C_β bond of the acyclic residues, although sterically less favorable than the (+)‐synclinal conformation, was imposed by the (R)‐bicyclic amino carbamoyl (BAC) residue. This highlighted the strong ability of the BAC residue to drive helical folding in heterochiral compounds. The role of the stereochemistry of the BAC unit was assessed and a model was proposed to explain the misfolding of the S/S sequences.     

Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies

Majucin‐type sesquiterpenes from Illicium sp., such as jiadifenolide ( 2 ), jiadifenin ( 3 ), and (1R,10S)‐2‐oxo‐3,4‐dehydroxyneomajucin ( 4 , ODNM), possess a complex caged chemical architecture and remarkable neurotrophic activities. As such, they represent attractive small‐molecule leads against various neurodegenerative diseases. We present an efficient, enantioselective, and unified synthesis of 2 , 3 , and 4 and designed analogues that diverge from tetracyclic key intermediate 7 . The synthesis of 7 is highlighted by the use of an enantioselective Robinson annulation reaction (construction of the AB rings), a Pd‐mediated carbomethoxylation reaction (construction of the C ring), and a one‐pot oxidative reaction cascade (construction of the D ring). Evaluation of the neurotrophic activity of these compounds led to the identification of several highly potent small molecules that significantly enhanced the activity of nerve growth factor (NGF) in PC‐12 cells. Moreover, efforts to define the common pharmacophoric motif suggest that substitution at the C‐10 center significantly affects bioactivity, while the hemiketal moiety of 2 and 3 and the C‐1 substitution might not be critical to the neurotrophic activity.     

Molecular Dynamics in 1- and 2-D Confinement as Studied for the Case of Poly(Cis-1,4-Isoprene)

Broadband Dielectric Spectroscopy (BDS) is used to probe the molecular dynamics of Type A polymer, poly(cis-1,4-isoprene), when confined in the 1-dimensional (1D) exploring space of thin layers and the 2-dimensional (2D) constraining geometry of unidirectional anodic aluminum oxide (AAO) nanopores. For both cases, it was observed that the structural relaxation remains bulk-like in its mean relaxation rate, although the distribution of its relaxation times is broadened in 2D confinement. Furthermore, the fluctuation of the end-to-end vector is interrupted, with the 1D case being relatively less pronounced. By this clear-cut comparison, it is demonstrated that the effects of confinement on molecular dynamics depend, inter alia, on the dimensionality of the restricting space.     

Tailoring the dielectric properties and energy storage density of 1−x(0.94NaNbO3−0.06SZ)−xBi2O3 through substitution strategy

Energy storage using dielectric capacitors is a growing area of research and development. However, designing a highly performing dielectric capacitor is still a challenge. Despite the excellent results achieved in lead-based dielectrics, lead-free substitutes are essential because of the environmental concerns associated with lead-based products. The lead-free 1?x (0.94NaNbO₃? 0.06SrZrO₃)+ x Bi₂O₃ ceramics abbreviated NNSZ + xB for x = 0.0, 0.05, 0.1, 0.15, and 0.20 was fabricated via solid-state reaction. A recoverable energy density of 2.93 J cm?³ was obtained for NNSZ+0.1B, associated with high thermal stability (25–130 °C), excellent cycling (N = 10⁵), and high efficiency (η) of 83.5%. Moreover, the introduction of Bi₂O₃ significantly improved the electrical insulation (?_r at 1 kHz = 1608 and tan δ = 0.0038) and breakdown strength (380 kVcm?¹) of NNSZ+0.1B by minimizing the formation of sodium, bismuth, and oxygen vacancies. The results obtained in this study provide a benchmark for further investigations on NaNbO₃-based ceramics. More importantly, this study suggests that NNSZ + xB ceramics can be used in pulsed power technology.     

Active mode locking of continuous-wave doubly and singly resonant optical parametric oscillators

We report on what we believe to be the first active mode locking of near-degenerate, doubly and singly resonant cw-pumped optical parametric oscillators (OPOs). We show experimentally that a steady-state regime of short pulses is reached in a few tens of microseconds under cw pumping. The oscillation buildup dynamics of both OPOs is also explored, evidencing an unusual transient behavior in the mode-locking process.     

The turnpike property in finite-dimensional nonlinear optimal control

Turnpike properties have been established long time ago in finite-dimensional optimal control problems arising in econometry. They refer to the fact that, under quite general assumptions, the optimal solutions of a given optimal control problem settled in large time consist approximately of three pieces, the first and the last of which being transient short-time arcs, and the middle piece being a long-time arc staying exponentially close to the optimal steady-state solution of an associated static optimal control problem. We provide in this paper a general version of a turnpike theorem, valuable for nonlinear dynamics without any specific assumption, and for very general terminal conditions. Not only the optimal trajectory is shown to remain exponentially close to a steady-state, but also the corresponding adjoint vector of the Pontryagin maximum principle. The exponential closedness is quantified with the use of appropriate normal forms of Riccati equations. We show then how the property on the adjoint vector can be adequately used in order to initialize successfully a numerical direct method, or a shooting method. In particular, we provide an appropriate variant of the usual shooting method in which we initialize the adjoint vector, not at the initial time, but at the middle of the trajectory.