Synthesis and NMR elucidation of novel pentacyclo-undecane diamine ligands

The synthesis and NMR elucidation of eight novel pentacyclo-undecane (PCU) diamine compounds are reported. These ligands are potential anti-inflammatory agents to be used against rheumatoid arthritis (RA). One-dimensional NMR techniques (¹H and ¹³C spectra) show major overlapping of methine resonances of the “cage” (PCU) thereby making it extremely difficult to assign all NMR signals. This overlapping occurs as a result of the substitutions made at the quaternary carbons (C-8/C-11) of the cage. Two-dimensional NMR techniques proved to be a useful tool in overcoming this problem.     

Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds

The rational development of multinuclear arene ruthenium complexes (arene = p-cymene, hexamethylbenzene) from generation 1 (G¹) and generation 2 (G²) of 4-iminopyridyl based poly(propyleneimine) dendrimer scaffolds of the type, DAB-(NH₂)_n (n = 4 or 8, DAB = diaminobutane) has been accomplished in order to exploit the ‘enhanced permeability and retention’ (EPR) effect that allows large molecules to selectively enter cancer cells. Four compounds were synthesised, i.e. [{(p-cymene)RuCl₂}₄G¹] (1), [{(hexamethylbenzene)RuCl₂}₄G¹] (2), [{(p-cymene)RuCl₂}₈G²] (3), and [{(hexamethylbenzene)RuCl₂}₈G²] (4), by first reacting DAB-(NH₂)_n with 4-pyridinecarboxaldehyde and subsequently metallating the iminopyridyl dendrimers with [(p-cymene)RuCl₂]₂ or [(hexamethylbenzene)RuCl₂]₂. The related mononuclear complexes [(p-cymene)RuCl₂(L)] (5) and [(hexamethylbenzene)RuCl₂(L)] (6) were obtained in a similar manner from N-(pyridin-4-ylmethylene)propan-1-amine (L). The molecular structure of 5 has been determined by X-ray diffraction analysis and the in vitro anticancer activities of the mono-, tetra- and octanuclear complexes 1–6 studied on the A2780 human ovarian carcinoma cell line showing a close correlation between the size of the compound and cytotoxicity.     

Chiral Hetero‐ and Carbocyclic Compounds from the Asymmetric Hydrogenation of Cyclic Alkenes

Several types of chiral hetero‐ and carbocyclic compounds have been synthesized by using the asymmetric hydrogenation of cyclic alkenes. N,P‐Ligated iridium catalysts reduced six‐membered cyclic alkenes with various substituents and heterofunctionality in good to excellent enantioselectivity, whereas the reduction of five‐membered cyclic alkenes was generally less selective, giving modest enantiomeric excesses. The stereoselectivity of the hydrogenation depended more strongly on the substrate structure for the five‐ rather than the six‐membered cyclic alkenes. The major enantiomer formed in the reduction of six‐membered alkenes could be predicted from a selectivity model and isomeric alkenes had complementary enantioselectivity, giving opposite optical isomers upon hydrogenation. The utility of the reaction was demonstrated by using it as a key step in the preparation of chiral 1,3‐cis‐cyclohexane carboxylates.     

The Role of Pressure During Shearing, Dissipative Collapse

We analyse a new family of solutions to the Einstein field equations describing the collapse of a fluid sphere in the presence of heat flux and shear. These solutions ensure that the collapsing fluid is accelerating and provide a generalisation of the geodesic fluid models studied in earlier treatments. In particular, we demonstrate the role played by pressure in the dynamics of the collapse process.     

Facile synthesis of Fmoc-N-methylated α- and β-amino acids

A highly efficient and environmentally friendly synthesis of Fmoc-N-methyl α- and β-amino acids from the corresponding Fmoc-amino acid, via intermediate oxazolidinones/oxazinanones, has been developed. Microwave heating for 3 min was required for the synthesis of the oxazinanones, while their Lewis acid catalyzed reductive opening only needed 1 min for completion. Hence, Fmoc-N-methyl-amino acids, suitable for, for example, solid phase peptide synthesis, can be readily prepared from the corresponding Fmoc amino acid in less than 1 h including purification. Fmoc-β³-homophenyl alanine showed unanticipated reactivity, and provided a one-step route to the highly useful Fmoc-protected 1,2,3,4-tetrahydroisoquinolineaceticacid, that is a β-hTic analogue.     

The excess molar volumes of (an alkanol + a branched chain ether) at the temperature 298.15 K and the application of the ERAS model

The excess molar volumes V_m^E {x(CH₃OH or CH₃CH₂OH or CH₃(CH₂)₂OH or CH₃CH(OH)CH₃ + (1 - x){CH₃(CH₂)₂}₂O or CH₃C(CH₃)₂OCH₃ or CH₃CH₂C(CH₃)₂OCH₃} have been calculated from measured values of density over the whole composition range at the temperature 298.15 K in order to investigate OH … O specific interactions. The results are explained in terms of the strong self-association of the alkanols, the specific interaction between the alkanol, and the ether molecules and packing effects upon mixing. The experimental V_m^h results presented here, together with the previously reported data for the molar excess enthalpy H_m^E, has been used to test the Extended Real Associated Solution (ERAS) model.     

Dissipative Collapse in the Presence of Λ

We present the general junction conditions for the smooth matching of a spherically symmetric, shear-free spacetime to Vaidya’s outgoing metric across a four-dimensional time-like hypersurface in the presence of a cosmological constant. These results generalise earlier treatments by Santos and co-workers on radiating stellar models. We study the thermal evolution of a particular radiating model within the framework of extended irreversible thermodynamics.     

The Driving Force for the Acylation of β-Lactam Antibiotics by L,D-Transpeptidase 2: Quantum Mechanics/Molecular Mechanics (QM/MM) Study

β-lactam antibiotics, which are used to treat infectious diseases, are currently the most widely used class of antibiotics. This study focused on the chemical reactivity of five- and six-membered ring systems attached to the β-lactam ring. The ring strain energy (RSE), force constant (FC) of amide (C−N), acylation transition states and second-order perturbation stabilization energies of 13 basic structural units of β-lactam derivatives were computed using the M06-2X and G3/B3LYP multistep method. In the ring strain calculations, an isodesmic reaction scheme was used to obtain the total energies. RSE is relatively greater in the five-(1a–2c) compared to the six-membered ring systems except for 4b, which gives a RSE that is comparable to five-membered ring lactams. These variations were also observed in the calculated inter-atomic amide bond distances (C−N), which is why the six-membered ring lactams C−N bond are more rigid than those with five-membered ring lactams. The calculated ΔG^# values from the acylation reaction of the lactams (involving the S−H group of the cysteine active residue from L,D transpeptidase 2) revealed a faster rate of C−N cleavage in the five-membered ring lactams especially in the 1–2 derivatives (17.58 kcal mol⁻¹). This observation is also reflected in the calculated amide bond force constant (1.26 mDyn/A) indicating a weaker bond strength, suggesting that electronic factors (electron delocalization) play more of a role on reactivity of the β-lactam ring, than ring strain.     

Stability of Solutal Convection in a Gravity Modulated Mushy Layer During the Solidification of Binary Alloys

The linear stability theory is used to investigate analytically the effects of gravity modulation on solutal convection in the mushy layer of solidifying binary alloys. The gravitational field consists of a constant part and a sinusoidally varying part, which is synonymous to a vertically oscillating mushy layer subjected to constant gravity. The linear stability results are presented for both the synchronous and subharmonic solutions. It is demonstrated that up to the transition point between the synchronous and subharmonic regions, increasing the frequency of vibration rapidly stabilizes the solutal convection. Beyond the transition point, further increases in the frequency tend to destabilize the solutal convection, but gradually. It is also demonstrated that the effect of increasing the ratio of the Stefan number and the solid composition (₀) is to destabilize the solutal convection.     

On a Framework for Generating Nonstatic Solutions of the Einstein Field Equations

In this paper we present a simple generalisation of all spherically symmetric static solutions. We present a framework to obtain both anisotropic and isotropic models with and without a barotropic equation of state of the form p = . The nonstaticity in some models necessarily requires a nonzero heat flux which dictates the thermodynamics of our models.