NH Substituents Research Articles

Bifunctional Squaramides as Organocatalysts for Lactide Polymerization: Catalytic Performance and Comparison with Monofunctional Analogues

AbstractAmine‐functionalized squaramides 1 and 2 were prepared and shown to be suitable polymerization organocatalysts for the controlled ring‐opening polymerization (ROP) of l‐lactide (l‐LA) in the presence of an alcohol source such as BnOH (which acts as an initiator) to afford chain‐length‐controlled and narrow‐dispersion poly(l‐lactide) (PLLA) under mild reaction conditions. The ROP experimental and polymer analysis data are consistent with the action of 1 and 2 as bifunctional hydrogen‐bonding (HB) catalysts that are able to activate both the lactide monomer and initiator BnOH thanks to their dual HB acceptor and donor properties. As a comparison, aminosquaramide 3, a direct analogue of 1 but a weaker HB donor because of the absence of electron‐withdrawing NH substituents, displays little lactide ROP activity, which highlights the key role of monomer activation through HB in the present systems. Unlike aminosquaramides 1 and 2, related monofunctional squaramides 4 and 5 are inactive in l‐LA ROP in the presence of BnOH, but the addition of NEt3, as an external HB acceptor, allows the ROP to proceed with the production of well‐defined PLLA. A cooperative dual activation with an activated monomer/activated chain‐end mechanism is most likely operative in the lactide ROP mediated by 1 and 2 in the presence of BnOH.

Optimization of Bipyridinyl Pyrazole Scaffolds via Design, Synthesis and Screening of a New Series of ROS1 Kinase‐modulating Compounds

A series of rationally designed ROS1 tyrosine kinase inhibitors 6a–9b with bipyridinyl pyrazole scaffold was synthesized and screened. The scaffold itself has showed an exclusive selectivity profile over ROS1 closely related kinases, ALK and c‐Met. The aim of this study was to further explore the structure–activity relationships (SAR) of the bipyridinyl pyrazole core structure, and to improve its ROS1 inhibitory potency. The rational of this study was to explore the nature of the proposed binding site for the pyrazole NH substituents. Careful selections of pyrazole NH substituent groups along with their regioisomers were considered. The compounds exhibited high degree of potency, IC50 values of 21–159 nM. A detailed SAR of bipyridinyl pyrazole scaffold has been finally well established and the virtual screening strategy, through molecular docking, has been performed for this type of ROS1 kinase inhibitors and the docked poses along with the activity data have gone in consistent with SAR specifications.

On the NH Effect in Ruthenium‐Catalysed Hydrogenation of Ketones: Rational Design of Phosphine‐Amino‐Alcohol Ligands for Asymmetric Hydrogenation of Ketones

Redesign and reduce: The graphic shows some Ru complexes of tridentate ligands that do not contain NH substituents but can catalyse ketone reduction with zero-order dependence on ketone. In tridentate systems, a secondary amine, not a primary amine, promotes hydrogen activation. Leading on from these observations, the Ru complex of a phosphine-amino-alcohol shown above has been found to be a good hydrogenation catalyst.

Quantum chemistry predicted correlations between geometric isomerism (conformation) of OH and NH substituents and typical group frequencies of nucleic acid bases: cytosine

Results of a search for correlations between typical group mode frequencies and conformation of OH and NH substituents is reported. The study is based on quantum chemical data (HF/6-31G (d, p) and MP2 (full)/6-31G (d, p) approximations) of 13 isomers of cytosine. It is closely related to investigations of stability and energetics of all isomers of the more common nucleic acid bases, which revealed correlations between conformation (geometric isomerism) of OH and NH substituents on the one hand and conversion energies, relaxation of internal structural parameters, electric field gradients, etc. on the other hand. In the majority of cases alteration of conformation of these substituents is accompanied by systematic frequency shifts of stretching, in-plane and out-of-plane bending (torsional) modes conventionally assigned to such groups and by alteration of quantum chemically predicted estimates of harmonic valence force constants and structural parameters dominating the mode frequencies. For identification of group modes ‘fractional’ mass (other than ‘natural’ mass) isotope shifts of frequency and normal vectors proved useful. Likewise, estimation of effects of force constant and structural parameter alterations on frequency shifts by first order perturbation theory of the FG problem of partial structures contributed valuable insight into the origin of the shifts.

Energy Increment Method Based on Quantum Chemical Results: A General Recipe for Approximative Prediction of Isomerization and Tautomerization Energies of Pyrimidine and Purine Nucleic Acid Bases and Related Compounds

On the basis of HF/6-31G(d,p) and MP2/6-31G(d,p) quantum chemical computations of fully optimized structures of all isomers of cytosine, isocytosine, uracil, thymine, adenine, guanine, xanthine, and many model compounds, a system of additive energy increments has been derived, from which energies of conversion of geometric isomers (conformers) and tautomers of these nucleic acid bases may be reconstructed within approximately 0.5 kcal/mol. The increments are associated with specific structural fragments perceptible in the conventional structural formula. Physically, they correspond to repulsions between H atoms of −OH, −NH2, and NH substituents and H atoms bound to C or N ring atoms and to attractions between H atoms of such substituents and sp2 lone electron pairs localized at N atoms of the ring systems or of imino substituents. Tautomerization energies associated with displacements of H atoms among ring N atoms were included in the estimation process of the increments. Keto−enol and amino−imino tautomerization energies may be estimated from total electronic energies and increments of conformer conversion energies. The estimates also approximately apply for ΔU° (0) and ΔU° (T0) (free molecules). The extended data set allowed some global structural features of the nucleic acid bases (such as formally aromatic 6-rings), which influence certain increments specifically, to be discerned. The set of increments presented may serve as a basis of a rather general recipe for predictive estimation of conformer and tautomer conversion energies of a wide range of hydroxy- and amino-substituted aromatic nitrogen bases and of effects of geometric isomerism on energetics of intermolecular H bonding involving −OH, −NH2, and NH substituents and protonated keto groups.

Doubly- and triply-bridging ligands derived from 2-pyridone and 2-aminopyridine. Crystal and molecular structure of the 2-pyridylamido complex [Os3H(CO)9{µ3-NC5H4(NH)}]* formed from 2-aminopyridine and dodecacarbonyltriosmium

The bis(cyclo-octene) complex [Os3(CO)10(C8H14)2] at room temperature or [Os3(CO)12] at elevated temperatures reacts with 2-pyridone, 2-aminopyridine, and 2-(benzylamino)pyridine. The clusters [Os3H(CO)10(µ-NC5H4X)](X = O, NH, or NCH2Ph) were formed under the mildest conditions and adopt structures directly corresponding with that of the acetato-complex [Os3H(CO)10(µ-O2CCH3)]. Unlike the µ-acetato-complex, however, these readily decarbonylate thermally to give [Os3H(CO)9(µ3-NC5H4X)]. The crystal and molecular structure of [Os3H(CO)9{µ3-NC5H4(NH)}] has been determined by X-ray methods. The crystals are monoclinic, space group P21/n, a= 8.497(2), b= 15.019(2), c= 15.649(7)A, β= 103.47(3)°, and Z= 4. The structure was refined to R= 0.0473 for 2 735 observed reflections. The pyridine ring is co-ordinated at one osmium atom while the NH substituent bridges the other two equivalent osmium atoms. The hydride ligand lies on the molecular plane of symmetry and bridges these equivalent osmium atoms. Decarbonylation of the decacarbonyl complex [Os3H(CO)10{µ-NC5H4(NCH2Ph)}] partly occurs in the same way but also gives the ortho-metallated complex [OS3H2(CO)9{µ-NC5H4(NCH2C6H4)}], isomeric with [Os3H(CO)9{µ3-NC5H4(NCH2Ph)}]. Vigorous treatment of [Os3(CO)12] with an excess of the 2-substituted pyridines gives the dinuclear species, [Os2(CO)6(µ-NC5H4X)2](X = 0 or NH), which exist as cis and trans isomers. Amphoteric behaviour is illustrated by the reversible addition of PMe2Ph to the 2-aminopyridine derivative [OS3H(CO)9(µ3-NC5H4X)](X = NH) and by its single and double protonations at osmium.