Hgands activation

Transmembrane receptors include G-protein-coupled receptors, receptor tyrosine kinases, integrins, pattern-recognition receptors and hgand-activated ion channels. 

Receptors for steroid hormones located in the nucleus. These are hgand-activated transcription factors. See Lavery, D.N. and McEwan, I.J., Structure and functions of steroid receptor AFl transactivation domains induction of active conformations, Biochem. J. 391, 449 64, 2005. 

Scott RH, Sweeney MI, Kobrinsky EM, Pearson HA, Timms GH, PuUar LA, Wedley S, Dolphin AC. Actions of arginine polyamine on voltage and hgand-activated whole cell currents recorded from cultured neurones. Br J Pharmacol 1992 106(l) 199-207. 

Mitoma J, Petryniak B, Hiraoka N, Yeh JC, Lowe JB, Fukuda M. Extended core 1 and core 2 branched O-glycans differentially modulate sialyl Lewis X-type L-selectin hgand activity. J Biol Chem 2003 278 9953-9961. 

Walton, K. A. et aL Speeific phosphohpid oxidation products inhibit hgand activation of toU-hke receptors 4 and 2.23, 1197—203, 2003. 

After an alignment of a set of molecules known to bind to the same receptor a comparative molecular field analysis CoMFA) makes it possible to determine and visuahze molecular interaction regions involved in hgand-receptor binding [51]. Further on, statistical methods such as partial least squares regression PLS) are applied to search for a correlation between CoMFA descriptors and biological activity. The CoMFA descriptors have been one of the most widely used set of descriptors. However, their apex has been reached. 

Complex 105 in an atmosphere of carbon monoxide experiences rearrangement to 106, which through C-H activation gives the final product 107 with i -coordiantion of the 3,4-diphosphacyclopentadienone hgand (97JCS(CC)1539). 

Significant advance in the field of asymmetric catalysis was also achieved with the preparation of l,2-bis(phospholano)benzene (DuPHOS 4) and its confor-mationally flexible derivative (l,2-bis(phospholano)ethane, known as BPE) by Burk et al. [59]. Two main distinctive features embodied by these Hgands, as compared to other known chiral diphosphine ligands, are the electron-rich character of the phosphorus atoms on the one hand and the pseudo-chirality at phosphorus atoms, on the other. These properties are responsible for both the high activity of the corresponding metal complex and an enantioselection indepen-... 

Pyridine-based N-containing ligands have been tested in order to extend the scope of the copper-catalyzed cyclopropanation reaction of olefins. Chelucci et al. [33] have carefully examined and reviewed [34] the efficiency of a number of chiral pyridine derivatives as bidentate Hgands (mainly 2,2 -bipyridines, 2,2 6, 2 -terpyridines, phenanthrolines and aminopyridine) in the copper-catalyzed cyclopropanation of styrene by ethyl diazoacetate. The corresponding copper complexes proved to be only moderately active and enantios-elective (ee up to 32% for a C2-symmetric bipyridine). The same authors prepared other chiral ligands with nitrogen donors such as 2,2 -bipyridines 21, 5,6-dihydro-1,10-phenanthrolines 22, and 1,10-phenanthrolines 23 (see Scheme 14) [35]. 

These N,N-chelating hgands were then covalently grafted on a modified Y-zeolite containing supermicropores . The selectivities observed were low (up to 11% ee) but led to similar values when comparing the imsupported and zeolite-supported Cu complexes. Interestingly, however, the zeolite catalysts could be recovered and reused several times with no loss of activity. 

These ligands were active for allyhc substitutions but the process was not enantioselective in the benchmark reaction (88, in Scheme 49). More structurally constrained chelates led, however, to measurable enantioselectivities 40% ee for 89, 50% ee for 90, and 64% ee for 91 in the test reaction. By further modifications in the structure of these bipyridine-type hgands (see 92 in Scheme 51, a chiral Ci-symmetric 2,2 -bipyridine) [126], enantioselectivities up to 89% were obtained. 

Efforts have been made to propose a heterogeneous version of this reaction by polymerization or support-anchoring of these N-containing hgands. In most cases, however, even if success was obtained by using these heterogeneous catalysts, their recycling remained non-efficient, mainly due to the poor stabihty of the active Pd(0) species. 

Encapsulation in Y zeohte was also the method chosen to immobihze Mn complexes of C2-symmetric tetradentate hgands (Fig. 24) [75]. These materials were used as catalysts for the enantioselective oxidation of sulfides to sulfoxides with NaOCl. The lack of activity when the larger io-dosylbenzene was used as an oxidant was interpreted as an indication that the reaction took place inside the zeolite microporous system. Both the chemo- and enantioselectivity were dependent on the structure of the sulfide. (2-Ethylbutyl)phenylsulfide led to better results than methylphenylsulfide, although in all cases the enantioselectivity was low (up to 21% ee). 

Iron(II) complex of tris(N -tert-butylurea-ylato)-N-ethylene]aminato activates dioxygen at room temperature to afford an iron(III) complex containing a single terminal oxo ligand. X-ray structures show that the three urea molecules act as a tridentate N,N,N-hgand [52]. The tripodal ligand was also used to synthesise complexes of cobalt, iron or zinc with terminal hydroxo ligands (Scheme 8) [53]. 

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