Ligand Lab Report

Fragment 7 is shown in the structure. Electron density map suggested two bulk electro-rich group present in the fragment, which corresponds to the two ring structure on 7. The heterocyclic ring has high e-density and forms a hydrophobic interaction with Leu144 residue. The e-rich NH2 group on this ring

The hydroxyl group set the directing effect for the product to have the iodine be placed para- to the hydroxyl group. IR spectrum showing a strong peak at 816.50 cmˉ¹ in the fingerprint region suggested a ring substitution pattern of 1, 2, 4- Trisubstituted because this pattern is expected to have peaks between 850- 800 cmˉ¹.

Once in the program Element and C was selected under the Builder Window, then center of the View1: New window was clicked to make a CH4 molecule appear.

The sulfonyl bound benzene (C8-C13) ring forms dihedral angles of 35.5(1)o and 65.6(1)o respectively, with the 2-formylpheneyl (C1-C6) and fluorophenyl (C18-C23) rings. The dihedral angle between fluorophenyl(C18-C23) and 2-formylphenyl(C1-C6) ring is 44.0(1)o. The structural parameter of MFMSF conforms to those reported for similar structure [31]. Fluorine atom F1 is deviated by -0.003(2) Å from the attached benzene ring. The hydrogen bond geometry for MFMSF is listed in Table.2. The molecular structure is stabilized by intramolecular C–H…π interaction between a sulfonyl-bound phenyl H9 atom and a fluorophenyl(C18-C23) ring with a C9–H9…Cg separation of 2.66Å, where Cg is the centroid of the C18-C23 fluorophenyl ring. Also, the molecular conformation is stabilized by weak intramolecular C9–H9...O3, C7–H7...N1 and C17–H17...O5 hydrogen bonds, each generates S(5) ring motifs [32]. In the crystal, four molecules are related by two intermolecular C10–H10…O1i and C25–H25A…O2ii hydrogen bonds, generating ring motifs [32] to form a two dimensional supramolecular network along [110] direction (Fig. 2; Symmetry codes as given in

One way to do this is to add a methyl or ethyl group at the 17a position or a methyl

The conformation is shown as an ORTEP diagram in Figure 4.2.The X-ray studies further showed that the terminal rings A and C are nearly planar, while the central ring B adopts a half-chair conformation. The average mean plane angle (Torsion angle) for the twist between the terminal rings A and C is 17.8º The X-ray studies further confirmed the Z geometry of molecule and nitrile group is present at syn position to oxygen in the ring C (Figure 4.2a). Crystal packing of (Z)-2-(2-(4-bromophenyl)-5,6-dihydro-4H-benzo[f]isochromen-4-ylidene)acetonitrile (7e) has shown some significant intermolecular interactions. It has been observed that moderate hydrogen bonding interaction (C-H••••Br = 2.991 Å) occurs between bromo (Br1) group and ortho hydrogen (H3) of ring D with the neighbouring molecules (Figure 4.2b).

phenylalanine) replaced Ala with more hydrophilic Gly, resulting in can be seen in the figure to

For this investigation, it is necessary to use a piece of software to accurately model the molecule and measure bond angles. This should provide the data necessary to ascertain

The M-C3 and C1- C2 single bonds are broken to form a metal alkylidene and ethylene.

web-based databases zinc docking org. (www. zinc.docking.org) The ligand geometries were optimized with the Powel method using the Tripos force field and Gasteiger-Hückel charges for all atoms, until a gradient 0.01 kcal/mol/Å was

Meta indicates two electrophiles on the first and third carbon and para is the first and fourth carbon. For this lab Ortho-para directors where the focus due to activation. Activation is the process by which activating substituent groups a stabilize the cationic intermediate after the addition of the first electrophile substituents. Activating substituents donate electrons to the cationic intermediate to stabilize the ring. The extra electrons are stored only on carbons 2,4 and 6, hence ortho-para directing of the second electrophilic substituent. Depending on the strength of the activator one or two electrophilic substituents may be added to the benzene

Besides the two catalytic residues Glu165 and Glu373, four mainly hydrophobic amino acids (His120, Phe121, Trp417 and Trp425) and Gln17, Arg75, Asn164, Tyr309 and Glu424, are grouped around the binding site.

It is notable that HDAC8 does not have an aromatic hydrophobic pocket corresponding to the one created by His-33 and Phe-155. In HDAC2 this region forms a nice groove, which is not observed in HDAC8, for the indole ring sit in. In HDAC8 the Lys-33 residue, while it has a hydrophobic chain, does not participate in staking interactions. The imidazole ring now adopts a T-shaped π-π stacking interaction between Phe-152 and Phe-208, whereas it was parallel displaced in HDAC2. This less favored double T-shaped interaction prevents the formation of a hydrogen bond in the core of HDAC8. ETS2 in HDAC8 also shows the shift of the indole ring to the right side of the gorge to now hydrogen bond with Gly-184, and the oxazole ring also adopts more of a T-shaped orientation with the Phe-208 in HDAC8 compared to a parallel π-π orientation. The oxazole ring is also less of an equal distance between the two Phe rings, favoring an interaction with Phe-208 over an interaction with Phe-152. Again the wider gorge size of HDAC8 decreases binding affinity of these compounds.

-Ligand is an ion or molecule which bonds to the central atom or ion of a compound.

According to the results discussed so far, including data presented in Figures 5, 6, and 7 and Tables 3 and 4, ZINC00936598, ZINC01020370, and ZINC00869973 compounds have the strongest linkage with the PR binding site residues among the natural compounds and all three compounds have more negative binding energy than the best-docked control drug (Levonorgestrel), in order to bind the PR binding cavity key residues. Furthermore, investigation of the interactions of these natural compounds reveals that whereas these compounds have the highest binding energy, PR binding site key residues that interact with these ligands were the same in all three cases reflecting the significant role of Glu23, Pro24, Asp25, Val26, Ile27, Gln53, Ser56, Val57,