The crystal structure of the dopamine D3 receptor (D3R) in complex with eticlopride inspired the design of bitopic ligands that explored (1) N-alkylation of the eticlopride’s pyrrolidine ring, (2) shifting of the position of the pyrrolidine nitrogen, (3) expansion of the pyrrolidine ring system, and (4) incorporation of O-alkylations at the 4-position. Structure activity relationships (SAR) revealed that moving the N- or expanding the pyrrolidine ring was detrimental to D2R/D3R binding affinities. Small pyrrolidine N-alkyl groups were poorly tolerated, but the addition of a linker and secondary pharmacophore (SP) improved affinities. Moreover, O-alkylated analogues showed higher binding affinities compared to analogously N-alkylated compounds, e.g., O-alkylated 33 (D3R, 0.436 nM and D2R, 1.77 nM) vs the N-alkylated 11 (D3R, 6.97 nM and D2R, 25.3 nM). All lead molecules were functional D2R/D3R antagonists. Molecular models confirmed that 4-position modifications would be well-tolerated for future D2R/D3R bioconjugate tools that require long linkers and or sterically bulky groups.

Molecular dynamics (MD) simulations were used to predict the thermal conductivity of β-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (β-HMX) along directions normal to the (011), (110), and (010) crystal planes. These directions were selected based on the measured morphological importance of the corresponding crystal surfaces. A reverse non-equilibrium MD approach was used wherein a constant heat flux is imposed along a prescribed direction and the resulting steady-state temperature gradient determined. The coefficient of thermal conductivity λ is the quotient of heat flux and temperature gradient (i.e. Fourier's law). Finite-size effects and sensitivity to imposed heat flux were investigated. The results reveal a modest dependence of the conductivity on crystal orientation, significant finite-size effects, and low sensitivity to imposed flux so long as the Fourier's law analysis is limited to the spatial interval in the simulation cell for which the temperature gradient is constant. Infinite-length thermal conductivities were estimated by linear regression of λ −1 (L) versus reciprocal cell length L −1 for each direction. The predicted values are systematically larger, but within a factor of two, than most published experimental determinations, the latter of which were obtained for pressed-powder or composite samples rather than oriented single crystals.

Density functional theory (DFT) and correlated molecular orbital electronic structure calculations were used to study the Al + CO → AlO + CO reaction on the electronic ground-state potential-energy surface (PES). Geometries were optimized using DFT (M11/jun-cc-pV(Q+d)Z) and more accurate energies were obtained using the composite Weizmann-1 theory with Brueckner doubles (W1BD). The results comprise the most complete, most systematic characterization of the Al + CO reaction surface to date and are based on consistent application of high-level methods for all stationary points identified. The pathways from Al + CO to AlO + CO on the electronic ground-state PES all involve formation of one or more stable AlCO complexes denoted η-AlCO, trans-AlCO, and C-AlCO, among which η-AlCO and C-AlCO are the least and most stable, respectively. We report a new minimum-energy pathway for the overall reaction, namely formation of η-AlCO from reactants and dissociation of that same complex to products via a bond-insertion reaction that passes through a fourth (weakly metastable) AlCO complex denoted cis-OAlCO. Natural Bond Orbital analysis was applied to study trends in charge distribution and the degree of charge transfer in key structures along the minimum-energy pathway. The process of aluminum insertion into CO is discussed in the context of analogous processes for boron and first-row transition metals.

Adsorption of molecular hydrogen on single-walled carbon nanotube (SWCNT), sulfur-intercalated SWCNT (S-SWCNT), and boron-doped SWCNT (BSWCNT), have been studied by means of density functional theory (DFT). Two methods KMLYP and local density approximation (LDA) were used to calculate the binding energies. The most stable configuration of H 2 on the surface of pristine SWCNT was found to be on the top of a hexagonal at a distance of 3.54 Å in good agreement with the value of 3.44 Å reported by Han and Lee (Carbon, 2004(Carbon, , 42, 2169. KMLYP binding energies for the most stable configurations in cases of pristine SWCNT, S-SWCNT, and BSWCNT were found to be -2.2 kJ mol -1 , -3.5 kJ mol -1 , and -3.5 kJ mol -1 , respectively, while LDA binding energies were found to be -8.8 kJ mol -1 , -9.7 kJ mol -1 , and -4.1 kJ mol -1 , respectively. Increasing the polarizability of hydrogen molecule due to the presence of sulfur in sulfur intercalated SWCNT caused changes in the character of its bonding to sulfur atom and affected the binding energy. In H 2 -BSWCNT system, stronger charge transfer caused stronger interaction between H 2 and BSWCNT to result a higher binding energy relative to the binding energy for H 2 -SWCNT .