Solvothermal Synthesis and Crystal Structure of a Layered Thioantimonate(Ⅲ) [C4H9NH3]2Sb4S7

An inorganic-organic hybrid thioantimonate(Ⅲ) [CH3(CH2)3NH3]2Sb4S7 1 with layered structure was synthesized by solvothermal method.1 crystallizes in the triclinic system, space group P with a = 7.0124(11), b = 11.919(2), c = 14.879(3) (A), α = 108.791(3), β = 102.441(3), γ = 92.846(2)o, V = 1140.1(3) (A)3, Mr = 859.71, Z = 2, Dc = 2.504 g/cm3, μ= 5.324 mm-1, F(000) = 804, S = 1.013, the final R = 0.0297 and wR = 0.0618 for 3534 observed reflections with I＞2σ(I). 1 consists of [C4H9NH3] cations and two-dimensional [Sb4S7]n2n-anion which is composed of three SbS3 trigonal pyramids and one SbS4 unit joined by sharing common corners. The anionic layers are stacked perpendicularly to the c axis of the unit cell forming two-dimensional channels between the layers. The [C4H9NH3] cations interdigitate in a bilayer and reside in the 2D channels leading to a sandwich-like arrangement of the anion and cations.     

Solvothermal Synthesis and Crystal Structure of a Layered Thioantimonate(Ⅲ) [C_4H_9NH_3]_2Sb_4S_7

An inorganic-organic hybrid thioantimonate(Ⅲ) [CH3(CH2)3NH3]2Sb4S7 1 with layered structure was synthesized by solvothermal method. 1 crystallizes in the triclinic system,space group P1 with a=7.0124(11),b=11.919(2),c=14.879(3),α=108.791(3),β=102.441(3),γ=92.846(2)o,V=1140.1(3)3,Mr=859.71,Z=2,Dc=2.504 g/cm3,μ =5.324 mm-1,F(000)=804,S=1.013,the final R=0.0297 and wR=0.0618 for 3534 observed reflections with I > 2σ(I). 1 consists of [C4H9NH3]+ cations and two-dimensional [Sb4S7]n2n- anion which is composed of three SbS3 trigonal pyramids and one SbS4 unit joined by sharing common corners. The anionic layers are stacked perpendicularly to the c axis of the unit cell forming two-dimensional channels between the layers. The [C4H9NH3]+ cations interdigitate in a bilayer and reside in the 2D channels leading to a sandwich-like arrangement of the anion and cations.     

Lipophilicity in PK design: methyl, ethyl, futile

Lipophilicity, often expressed as distribution coefficients (log D) in octanol/water, is an important physicochemical parameter influencing processes such as oral absorption, brain uptake and various pharmacokinetic (PK) properties. Increasing log D values increases oral absorption, plasma protein binding and volume of distribution. However, more lipophilic compounds also become more vulnerable to P450 metabolism, leading to higher clearance. Molecular size and hydrogen bonding capacity are two other properties often considered as important for membrane permeation and pharmacokinetics. Interrelationships among these physicochemical properties are discussed. Increasing size (molecular weight) often gives higher potency, but inevitably also leads to either higher lipophilicity, and hence poorer dissolution/solubility, or to more hydrogen bonding capacity, which limits oral absorption. Differences in optimal properties between gastrointestinal absorption and uptake into the brain are addressed. Special attention is given to the desired lipophilicity of CNS drugs. In examples using -blockers, Ca channel antagonists and peptidic renin inhibitors we will demonstrate how potency and pharmacokinetic properties need to be balanced.     

The Structure of New Host Molecules that form Channel Inclusion Compounds

1,3-Benzenediamine,N,N′-bis(4,6-dichloro-1,3,5-triazine-2-yl) and 1,3,5-Triazine,2,2′-[2-methyl-1,3-phenylenebis(oxy)] bis(4,6-dichloro) were synthesized as host molecules. The inclusion compound of 1,3-Benzenediamine,N,N′-bis(4,6-dichloro-1,3,5-triazine-2-yl) crystallizes in the monoclinic crystal system in space group C2/c. The host molecule occupies the space group 2-fold special position and packed in the crystal lattice in such a manner as to leave channels running along the c axis of a rectangular cross-section. It crystallizes with two molecules of acetone that are hydrogen bonded to the amino nitrogen atoms. Molecules of 1,3,5-Triazine,2,2′-[2-methyl-1,3-phenylene bis(oxy)]bis(4,6-dichloro) are packed in the crystal in such a manner as to leave channels of a trapezoid cross-section that are running along the a axis. Guest molecules such as metanol, ethanol, and ethyl acetate can be used to fill the channels. The crystal structures of two inclusion compounds are described.     

Simulations of the active transport of a neutral solute based on a kinase-channel-phosphatase topology

Simulations of coupled interactions involving two opposite enzymatic reactions, solute diffusions, and electrostatic interactions between membrane charges and charged solutes were conducted under a fixed kinase-channel-phosphatase (KCP) topology oriented from the outside to the inside of a porous membrane structure. Depending on the kinase and phosphatase locations, we recently demonstrated that an active transport of a phosphorylated substrate may occur via the opposite topology, that is, a PCK topology. The present analysis demonstrates that, under a KCP membrane topology, which also behaves as a specific ATP-dependent transporter, the active transport of a neutral substrate may occur. This analogous active transport appears to be dependent on the phosphatase location and on the membrane surface potentials. A broad analysis of the role played by the main parameters taken into account in the model was conducted in order to define precisely the physico-chemical conditions and the membrane topology needed for the highest active transports within the shortest time.     

Structure-activity relationship of Ca2+ channel blockers: A study using conformational analysis and chemometric methods

Summary A structure-activity relationship study has been done on 8 compounds with the activity known as Ca²⁺ channel blockers. Conformational analysis was carried out using a molecular mechanics method. The 3D-QSAR approach was used and the most polar functional groups present in all the molecules were considered. Eight interatomic distances are necessary to define the relative spatial disposition of these relevant molecular fragments. The structure-activity relationship between interatomic distances and biological activity was performed using statistic and chemometric methods. In particular, with Principal Component Analysis, it was possible to reduce the number of interatomic distances: only six of the eight distances are sufficient to describe the system in a useful way. A classification method was iteratively used to select the most probable conformations linked to the biological activity and to build a model able to classify conformations according to their biological behaviour. Cluster analysis on the active selected conformations subsequently allowed the identification of two different geometrical patterns for the active compounds. Finally the validity of the model was verified by correctly predicting the activity of other molecules not used in the construction of the model but possessing known activity.     

An approach to channel type molecular structures. 1. Synthesis ofBouquet-shaped molecules based on an [18]-O6 polyether macrocycle

An approach to a transmembrane cation channel is described. It is based on the grafting of oxygen bearing side-chains on a macrocyclic polyether unit that constitutes the organizing core. The resulting species has a structure of overall bouquet shape. The synthesis of such a molecule . _M ⁰ ,14a is described, together with that of its analogue bearing polymethylene side-chains _M ^C ,14b. The physicochemical properties of these molecules indicate that they possess the features expected on the basis of their structure.This paper is dedicated to the memory of the late Dr C. J. Pedersen.