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The title compound (systematic name: pyridinium 4-methylbenzenesulfonate), C5H6N+·C7H7O3S−, is the pyridinium salt of para-toluenesulfonic acid. In the crystal, classical N—H...O hydrogen bonds as well as C—H...O contacts connect the cationic and anionic entities into sheets lying parallel to the ab plane.

The title compound (systematic name: rac-2-hydroxy-3-methylbutanoic acid), C5H10O3, is the constitutional isomer of α-hydroxybutanoic acid. In the crystal, hydrogen bonds involving the alcoholic hydroxyl group give rise to centrosymmetric dimers that are extended to sheets perpendicular to the crystallographic c axis.

The title compound, C12H22O2, is a symmetric diol derived from the pinacol coupling of cyclohexanone. The asymmetric unit contains three complete molecules. The cyclohexane moieties adopt chair conformations. Cooperative hydrogen bonding connects the individual molecules to infinite chains propagating along the crystallographic a-axis direction.

Development of biased ligands targeting G protein-coupled receptors (GPCRs) is a promising approach for current drug discovery. Although structure-based drug design of biased agonists remains challenging even with an abundance of GPCR crystal structures, we present an approach for translating GPCR structural data into β-arrestin-biased ligands for aminergic GPCRs. We identified specific amino acid-ligand contacts at transmembrane helix 5 (TM5) and extracellular loop 2 (EL2) responsible for Gi/o and β-arrestin signaling, respectively, and targeted those residues to develop biased ligands. For these ligands, we found that bias is conserved at other aminergic GPCRs that retain similar residues at TM5 and EL2. Our approach provides a template for generating arrestin-biased ligands by modifying predicted ligand interactions that block TM5 interactions and promote EL2 interactions. This strategy may facilitate the structure-guided design of arrestin-biased ligands at other GPCRs, including polypharmacological biased ligands.

The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP.

C6H4BrNO2, orthorhombic, Pna21 (no. 33), a = 21.3992(17) Å, b = 5.9311(4) Å, c = 5.2923(4) Å, V = 671.70(9) Å3, Z = 4, R gt(F) = 0.0284, wR ref(F 2) = 0.0708, T = 200(2) K.

C8H14O5S, monoclinic, P21 (no. 4), a = 6.3783(4) Å, b = 8.2630(5) Å, c = 10.5891(7) Å, β = 90.877(2)°, V = 558.02(6) Å3, Z = 2, Rgt(F) = 0.0254, wRref(F2) = 0.0715, T = 200 K.

C17H30N2, tetragonal, P4‾$P‾{4}$21m (no. 113), a = 8.6755(3) Å, c = 11.1611(4) Å, V = 840.03(7) Å3, Z = 2, Rgt(F) = 0.0488, wRref(F2) = 0.1417, T = 200 K.

C13H8O3S, monoclinic, C2/c (no. 15), a = 9.7499(3) Å, b = 12.9758(4) Å, c = 8.2681(3) Å, β = 103.784(2)°, V = 1015.90(6) Å3, Z = 4, Rgt(F) = 0.0318, wRref(F2) = 0.0927, T = 200 K.

C6H10Cl2N2O, triclinic, P1‾$‾{1}$ (no. 2), a = 4.8274(4) Å, b = 8.0556(7) Å, c = 12.0648(10) Å, α = 71.237(4)°, β = 78.739(4)°, γ = 72.950(4)°, V = 422.06(6) Å3, Z = 2, Rgt(F) = 0.0225, wRref(F2) = 0.0614, T = 190 K.

C12H9NS, monoclinic, P21/n (no. 14), a = 5.0743(5) Å, b = 14.0545(13) Å, c = 13.3319(17) Å, β = 91.102(5)°, V = 950.61(18) Å3, Z = 4, Rgt(F) = 0.0322, wRref(F2) = 0.0908, T = 200 K.

C8H18ClNO2, monoclinic, P21/c (no. 14), a = 6.8110(5) Å, b = 8.8779(7) Å, c = 17.2774(16) Å, β = 97.582(4)°, V = 1035.59(15) Å3, Z = 4, Rgt(F) = 0.0484, wRref(F2) = 0.0922, T = 200 K.

C6H8N2O6, monoclinic, P21/c (no. 14), a = 7.4709(4) Å, b = 14.2051(9) Å, c = 7.3198(4) Å, β$\beta $ = 97.096(4)°, V = 770.86(8) Å3, Z = 4, Rgt(F) = 0.0346, wRref(F2) = 0.0946, T = 200 K.

C21H18O2, triclinic, P1‾$‾{1}$ (no. 2), a = 9.8213(6) Å, b = 9.9212(6) Å, c = 10.0400(6) Å, α = 65.510(2)°, β = 63.539(2)°, γ = 84.842(2)°, V = 791.59(8) Å3, Z = 2, Rgt(F) = 0.0463, wRref(F2) = 0.1101, T = 200 K.

C7H9N, orthorhombic, Pna21 (no. 33), a = 8.9239(5) Å, b = 5.9550(3) Å, c = 23.1168(11) Å, V = 1228.47(11) Å3, Z = 8, Rgt(F) = 0.0367, wRref(F2) = 0.1019, T = 200 K.

C32H30N8O5, orthorhombic, P212121 (no. 19), a = 9.1258(4) Å, b = 10.6225(5) Å, c = 30.1870(14) Å, V = 2926.3(2) Å3, Z = 4, Rgt(F) = 0.0367, wRref(F2) = 0.0837, T = 200 K.

C4H11Cl2N, monoclinic, I2/a (no. 15), a = 13.2374(12) Å, b = 8.2108(6) Å, c = 14.0114(14) Å, β = 93.294(8)°, V = 1520.4(2) Å3, Z = 8, Rgt(F) = 0.0398, wRref(F2) = 0.1174, T = 200 K.

C14H14F6N2O, orthorhombic, Pbcn (no. 60), a = 17.7552(12) Å, b = 10.7574(9) Å, c = 8.0207(7) Å, V = 1532.0(2) Å3, Z = 4, Rgt(F) = 0.0415, wRref(F2) = 0.1154, T = 200 K.

C9H24N2O7, monoclinic, P21/n (no. 14), a = 11.1646(7) Å, b = 6.3264(4) Å, c = 18.6926(9) Å, β = 97.5994(18)°, V = 1308.69(13) Å3, Z = 4, Rgt(F) = 0.0385, wRref(F2) = 0.1057, T = 200 K.

C6H13Cl2N, orthorhombic, P212121 (no. 19), a = 6.0087(3) Å, b = 10.1176(6) Å, c = 14.3532(7) Å, V = 872.58(8) Å3, Z = 4, Rgt(F) = 0.0304, wRref(F2) = 0.0632, T = 200 K.

C18H28BrNO2, orthorhombic, P212121 (no. 19), a = 7.0417(4) Å, b = 9.1635(5) Å, c = 27.3371(15) Å, V = 1763.97(17) Å3, Z = 4, Rgt(F) = 0.0275, wRref(F2) = 0.0596, T = 200 K.

C12H12Cl4NSb, monoclinic, P21/n (no. 14), a = 5.6693(2) Å, b = 20.2385(7) Å, c = 14.3908(5) Å, β = 100.3830(10)°, V = 1624.14(10) Å3, Z = 4, Rgt(F) = 0.0192, wRref(F2) = 0.0430, T = 200 K.

C6H4Br2FN, monoclinic, P21/c (no. 14), a = 17.0332(5) Å, b = 4.34070(10) Å, c = 21.9732(5) Å, β = 109.6910(10)°, V = 1529.61(7) Å3, Z = 8, Rgt(F) = 0.0256, wRref(F2) = 0.0518, T = 200 K.

C6H15Cl2N, triclinic, P1‾$‾{1}$ (no. 2), a = 6.9579(4) Å, b = 8.1852(5) Å, c = 8.7912(5) Å, α = 66.606(2)°, β = 86.105(3)°, γ = 89.834(2)°, V = 458.30(5) Å3, Z = 2, Rgt(F) = 0.0226, wRref(F2) = 0.0599, T = 200 K.

C15H14O4, monoclinic, C2/c (no. 15), a = 27.1122(8) Å, b = 6.4295(2) Å, c = 14.7495(4) Å, β = 91.7070(10)°, V = 2569.96(13) Å3, Z = 8, Rgt(F) = 0.0387, wRref(F2) = 0.1091, T = 200 K.

C12H10O3Se2, triclinic, P1‾$‾{1}$ (no. 2), a = 9.1794(3) Å, b = 11.5706(5) Å, c = 12.3976(5) Å, α = 85.291(2)°, β = 72.198(2)°, γ = 74.084(2)°, V = 1205.65(8) Å3, Z = 4, Rgt(F) = 0.0275, wRref(F2) = 0.0698, T = 200 K.

C7H6BrNO2, orthorhombic, P212121 (no. 19), a = 4.7019(6) Å, b = 6.4700(9) Å, c = 25.283(4) Å, V = 769.14(19) Å3, Z = 4, Rgt(F) = 0.0294, wRref(F2) = 0.0671, T = 200 K.

C19H14ClNO2, monoclinic, P21/c (no. 14), a = 19.328(4) Å, b = 7.1086(12) Å, c = 11.627(2) Å, β = 99.417(9)°, V = 1576.0(5) Å3, Z = 4, Rgt(F) = 0.0582, wRref(F2) = 0.1615, T = 200 K.

C7H5BrO, monoclinic, P21/c (no. 14), a = 27.3992(18) Å, b = 3.9369(2) Å, c = 12.8006(8) Å, β = 103.504(2) Å, V = 1342.60(14) Å3, Z = 8, Rgt(F) = 0.0469, wRref(F2) = 0.1103, T = 200(2) K.

C5H10N2O, monoclinic, Ia (no. 9), a = 4.7212(4) Å, b = 11.1424(8) Å, c = 12.8211(9) Å, β = 94.349(3)°, V = 672.52(9) Å3, Z = 4, Rgt(F) = 0.0280, wRref(F2) = 0.0821, T = 200 K.

C8H8O2, tetragonal, P43212 (no. 96), a = 10.9521(5) Å, c = 23.3014(17) Å, V = 2795.0(3) Å3, Z = 16, Rgt(F) = 0.0317, wRref(F2) = 0.0883, T = 200 K.

C8H8O3, monoclinic, P21/c (no. 14), a = 6.3037(3) Å, b = 33.102(2) Å, c = 7.0471(4) Å, β = 102.105(3)°, V = 1437.79(14) Å3, Z = 8, Rgt(F) = 0.0433, wRref(F2) = 0.1087, T = 200 K.

C8H11ClN2S, orthorhombic, Pbca (no. 61), a = 11.3126(6) Å, b = 8.3567(4) Å, c = 20.4130(11) Å, V = 1929.76(17) Å3, Z = 8, Rgt(F) = 0.0240, wRref(F2) = 0.0680, T = 200 K.

C6H6ClN, monoclinic, P21/c (no. 14), a = 6.5211(2) Å, b = 10.2467(3) Å, c = 9.1436(3) Å, β = 94.1771(11)°, V = 609.35(3) Å3, Z = 4, Rgt(F) = 0.0260, wRref(F2) = 0.0680, T = 200 K.

C8H9NO2S, triclinic, P1¯$\overline{1}$ (no. 2), a = 6.6909(5) Å, b = 7.9787(6) Å, c = 8.5551(6) Å, α = 80.065(3)°, β = 68.175(3)°, γ = 77.676(4)°, V = 412.01(5) Å3, Z = 2, Rgt(F) = 0.0263, wRref(F2) = 0.0784, T = 200(2) K.

C17H10O, orthorhombic, P212121 (no. 19), a = 5.0604(12) Å, b = 14.672(3) Å, c = 14.846(3) Å, V = 1102.2(4) Å3, Z = 4, Rgt(F) = 0.0432, wRref(F2) = 0.1022, T = 200(2) K.

C14H15AsClNOS, monoclinic, P21 (no. 4), a = 5.2852(2) Å, b = 13.3035(6) Å, c = 10.7522(5) Å, β = 90.130(2) Å, V = 756.00(6) Å3, Z = 2, Rgt(F) = 0.0200, wRref(F2) = 0.0503, T = 200(2) K.

C14H13AsClNO2, triclinic, P1¯$\overline{1}$ (no. 2), a = 7.7180(7) Å, b = 8.2190(7) Å, c = 11.9620(10) Å, α = 87.438(4)°, β = 73.450(4)°, γ = 72.167(4)°, V = 691.66(10) Å3, Z = 2, Rgt(F) = 0.0203, wRref(F2) = 0.0541, T = 200 K.

C19H15N3O2, monoclinic, P21/c (no. 14), a = 18.4336(13) Å, b = 6.0321(4) Å, c = 15.0585(10) Å, β = 112.171(3)°, V = 1550.60(18) Å3, Z = 4, Rgt(F) = 0.0535, wRref(F2) = 0.1298, T = 200 K.

C9H13NO${\text{C}}_{9}{\text{H}}_{13}\text{NO}$, orthorhombic, Pbcn (no. 60), a = 29.554(4) Å, b = 7.4930(11) Å, c = 8.2800(10) Å, V = 1833.6(4) Å3, Z = 8, Rgt${R}_{gt}$(F) = 0.0737, wRref$w{R}_{ref}$(F2${F}^{2}$) = 0.1646, T = 200 K.

C3H5ClO2, monoclinic, P21/c (no. 14), a = 5.2011(4) Å, b = 7.4362(4) Å, c = 24.1175(15) Å, β = 94.594(3)°, V = 929.78(10) Å3, Z = 8, Rgt(F) = 0.0333, wRref(F2) = 0.0795, T = 200 K.

C14H16FeO, orthorhombic, P212121 (no. 19), a = 5.6954(3) Å, b = 10.0307(6) Å, c = 20.4422(14) Å, V = 1167.84(12) Å3, Z = 4, Rgt(F) = 0.0267, wRref(F2) = 0.0559, T = 200 K.

C9H10O3, orthorhombic, Pbca (no. 61), a = 14.2570(6) Å, b = 7.9250(4) Å, c = 29.8796(13) Å, V = 3376.0(3) Å3, Z = 16, Rgt(F) = 0.0404, wRref(F2) = 0.1050, T = 200 K.

C10H18O2, monoclinic, C2/c (no. 15), a = 10.0025(5) Å, b = 18.8285(9) Å, c = 11.2384(6) Å, β = 115.327(2)°, V = 1913.11(17) Å3, Z = 8, Rgt(F) = 0.0596, wRref(F2) = 0.1606, T = 200 K.

C6H10N2, triclinic, P1‾$‾{1}$ (no. 2), a = 7.4423(5) Å, b = 7.9420(5) Å, c = 11.6711(8) Å, α = 96.667(3)°, β = 95.650(3)°, γ = 100.999(3)°, V = 667.42(8) Å3, Z = 4, Rgt(F) = 0.0620, wRref(F2) = 0.1681, T = 200 K.

C45H35LaO7, trigonal, R3 (no. 146), a = 22.3832(11) Å, c = 6.4522(3) Å, V = 2799.5(3) Å3, Z = 3, Rgt(F) = 0.0192, wRref(F2) = 0.0462, T = 200 K.

C13H11NO, orthorhombic, Pca21 (no. 29), a = 23.801(4) Å, b = 6.0510(13) Å, c = 7.2677(14) Å, V = 1046.7(3) Å3, Z = 4, Rgt(F) = 0.0335, wRref (F2) = 0.0896, T = 200 K.

C8H9NO3, monoclinic, P21/n (no. 14), a = 6.9121(4) Å, b = 26.9700(15) Å, c = 8.7204(5) Å, β = 106.152(3)°, V = 1561.48(16) Å3, Z = 8, Rgt(F) = 0.0486, wRref(F2) = 0.1399, T = 200 K.

C7H3Cl3O, monoclinic, P21/c (no. 14), a = 12.0518(15) Å, b = 9.7403(11) Å, c = 6.9562(9) Å, β = 99.047(4)°, V = 806.42(17) Å3, Z = 4, Rgt(F) = 0.0316, wRref(F2) = 0.0793, T = 200 K.

C4H11NO2, monoclinic, P21/n (no. 14), a = 6.0864(4) Å, b = 10.9696(8) Å, c = 8.5928(5) Å, β = 93.360(3)°, V = 572.72(7) Å3, Z = 4, Rgt(F) = 0.0307, wRref(F2) = 0.0891, T = 200 K.