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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 11| November 2014| Pages o1149-o1150

Crystallographic study of PET radio­tracers in clinical evaluation for early diagnosis of Alzheimers

aIstituto di Cristallografia, Via G. Amendola, 122/o, 7016, Bari, Italy, bDip. di Farmacia-Scienze del Farmaco, Universita' degli studi di Bari, Via Orabona, 4, 70125, Bari, Italy, and cDip. di Farmacia-Scienze del Farmaco, Biofordrug, srl, Universita' degli studi di Bari, Via Orabona, 4, 70125, Bari, Italy
*Correspondence e-mail: rosanna.rizzi@ic.cnr.it

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 3 August 2014; accepted 26 September 2014; online 4 October 2014)

The title compound, C24H25NO3·2CH3OH, which crystallized as a methanol disolvate, has applications as a PET radiotracer in the early diagnosis of Alzheimer's disease. The dihedral angle between the biphenyl rings is 8.2 (2)° and the heterocyclic ring adopts a half-chair conformation with the N atom adopting a pyramidal geometry (bond-angle sum = 327.6°). The C atoms of both meth­oxy groups lie close to the plane of their attached ring [deviations = 0.107 (6) and 0.031 (6) Å]. In the crystal, the components are linked by O—H⋯O and O—H⋯N hydrogen bonds, generating [010] chains. C—H⋯O inter­actions are also observed.

1. Related literature

For pharmacological and biological studies of the title compound, see Colabufo et al. (2008[Colabufo, N. A., Berardi, F., Cantore, M., Perrone, M. G., Contino, M., Inglese, C., Niso, M., Perrone, R., Azzariti, A., Simone, G. M. & Paradiso, A. (2008). Bioorg. Med. Chem. 16, 3732-3743.], 2009[Colabufo, N. A., Berardi, F., Perrone, M. G., Cantore, M., Contino, M., Inglese, C., Niso, M. & Perrone, R. (2009). ChemMedChem, 4, 188-195.]).

[Scheme 1]

2. Experimental

2.1. Crystal data

  • C24H25NO3·2CH4O

  • Mr = 439.53

  • Monoclinic, P 21

  • a = 8.894 (2) Å

  • b = 13.7187 (16) Å

  • c = 10.680 (2) Å

  • β = 111.575 (17)°

  • V = 1211.8 (4) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.08 mm−1

  • T = 293 K

  • 0.30 × 0.30 × 0.15 mm

2.2. Data collection

  • Bruker–Nonius KappaCCD diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2008a[Sheldrick, G. M. (2008a). SADABS. University of Göttingen, Germany.]) Tmin = 0.921, Tmax = 0.988

  • 14813 measured reflections

  • 5436 independent reflections

  • 2610 reflections with I > 2σ(I)

  • Rint = 0.116

2.3. Refinement

  • R[F2 > 2σ(F2)] = 0.061

  • wR(F2) = 0.115

  • S = 0.96

  • 5436 reflections

  • 305 parameters

  • 1 restraint

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.17 e Å−3

  • Δρmin = −0.15 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O2—H2O⋯N1 0.94 (5) 1.87 (5) 2.812 (5) 178 (4)
O4—H4O⋯O5i 0.95 (6) 1.71 (6) 2.636 (6) 165 (5)
O5—H5O⋯O2 0.71 (8) 2.00 (8) 2.684 (6) 162 (9)
C15—H15A⋯O1ii 0.97 2.50 3.445 (6) 164
C23—H23A⋯O2iii 0.96 2.56 3.437 (6) 152
Symmetry codes: (i) x, y+1, z; (ii) [-x+1, y+{\script{1\over 2}}, -z]; (iii) [-x, y-{\script{1\over 2}}, -z].

Data collection: COLLECT (Nonius, 2002[Nonius (2002). COLLECT and EVAL. Nonius BV, Delft, The Netherlands.]); cell determination and refinement: DIRAX (Duisenberg,1992[Duisenberg, A. J. M. (1992). J. Appl. Cryst. 25, 92-96.]; Duisenberg et al., 2000[Duisenberg, A. J. M., Hooft, R. W. W., Schreurs, A. M. M. & Kroon, J. (2000). J. Appl. Cryst. 33, 893-898.]); data reduction: EVAL (Nonius, 2002[Nonius (2002). COLLECT and EVAL. Nonius BV, Delft, The Netherlands.]; Duisenberg et al., 2003[Duisenberg, A. J. M., Kroon-Batenburg, L. M. J. & Schreurs, A. M. M. (2003). J. Appl. Cryst. 36, 220-229.]); program(s) used to solve structure: SIR2011 (Burla et al., 2012[Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., Giacovazzo, C., Mallamo, M., Mazzone, A., Polidori, G. & Spagna, R. (2012). J. Appl. Cryst. 45, 357-361.]); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and EXPO2013 (Altomare et al., 2013[Altomare, A., Cuocci, C., Giacovazzo, C., Moliterni, A., Rizzi, R., Corriero, N. & Falcicchio, A. (2013). J. Appl. Cryst. 46, 1231-1235.]); software used to prepare material for publication: WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information


Comment top

The single-crystal X-ray structure solution of 4'-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl-methyl)-biphenyl-4-ol (named MC70) radiotracer, previously pharmacologically characterized and biologically evaluated (compound 4e in Colabufo et al., 2008, 2009), has been reported. At nanomolar concentrations MC70 is a potent inhibitor of P-glycoprotein (P-gp), a membrane protein playing a protective role of the central nervous system and whose numerical and functional alteration is responsible for the onset of the Alzheimer disease. The crystallographic characterization of MC70 represents the first necessary step for a further evaluation of its pharmacological properties and to obtain, f. e. through docking techniques and homology modelling, a tridimensional interpretation of the main molecular determinants responsible for most of MC70 features such as to be an inhibitor of the P-gp. The study of this behaviour will allow the design of new ligands, more effective and selective in the monitoring the role of P-glycoprotein for the recognition and early treatment of the Alzheimer disease. In addition, up to now none of the studies on interactions of this pump with known inhibitors, report crystallographic data of P-gp inhibitors complexes. Therefore speculating the binding conformation and pose for MC70 might be an added value to a better understanding of the mechanism of action of efflux pumps involved in the Alzheimer's disease.

A view of the refined crystal structure is shown in Figure 1. The packing of the obtained crystal structure is represented in Figure 2; it is interesting observing that the network of the structure features three hydrogen bonds (Table 1): the first between the 2 molecules of methanol, the second between one methanol molecule and the phenolic residue of the molecule and the last between the other methanol molecule and the isoquinoline nucleus. In the crystal weak C—H···O hydrogen bonds also occur. In addition, the pendant biphenyl has an equatorial configuration as proved by a dihedral angle among atoms C8—N1—C7—C18 of -175°.

Related literature top

For pharmacological and biological studies of the title compound, see Colabufo et al. (2008, 2009).

Experimental top

MC70, [4'-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl-methyl)-biphenyl-4-ol] (C24H25NO3) has been obtained after crystallization as yellow needles. The solvent/non-solvent diffusion has been used as crystallization technique: after solubilizing MC70 (5 mg) in methanol (solvent, 1 ml), an equal volume of CH2Cl2 (non-solvent, 1 ml) has been deposited. The vial has been covered with a perforated cap and left at room temperature. After a couple of days, yellow needles of MC70 2CH3OH have grown on the interphase solvent/non-solvent.

Refinement top

The hydrogen atoms of the hydroxyl groups were located by difference Fourier synthesis and freely isotropically refined. The C-bonded H atoms were positioned geometrically with C—H = 0.96, 0.97 and 0.93 Å for methyl, methylene and aromatic H atoms, respectively, and constrained to ride on their parent atoms. The constraint Uiso(H) = kUeq(C), where k = 1.5 for methyl and k = 1.2 for aromatic and methylene H atoms, was applied. The highest residual electron density was found 1.59 Å from C16 and the deepest hole 1.04 Å from H12A.

Computing details top

Data collection: COLLECT (Nonius, 2002); cell refinement: DIRAX (Duisenberg,1992; Duisenberg et al., 2000); data reduction: EVAL (Nonius, 2002; Duisenberg et al., 2003); program(s) used to solve structure: SIR2011 (Burla et al., 2012); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and EXPO2013 (Altomare et al., 2013); software used to prepare material for publication: WinGX (Farrugia, 2012) and publCIF (Westrip, 2010).

Figures top
Figure 1. The molecular structure of the MC70 compound with displacement ellipsoids drawn at the 50% probability level.

Figure 2. Crystal packing of the MC70 compound. The light blue dashed lines show the hydrogen bonds (see Table 1 for details).
4'-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl-methyl)-biphenyl-4-ol methanol disolvate top
Crystal data top
C24H25NO3·2CH4OF(000) = 472
Mr = 439.53Dx = 1.205 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 8.894 (2) ÅCell parameters from 130 reflections
b = 13.7187 (16) Åθ = 2.9–26.6°
c = 10.680 (2) ŵ = 0.08 mm1
β = 111.575 (17)°T = 293 K
V = 1211.8 (4) Å3Needle, yellow
Z = 20.30 × 0.30 × 0.15 mm
Data collection top
Bruker–Nonius KappaCCD
diffractometer
5436 independent reflections
Radiation source: fine-focus sealed tube2610 reflections with I > 2σ(I)
Detector resolution: 9.091 pixels mm-1Rint = 0.116
ϕ scans and ω scansθmax = 27.5°, θmin = 5.1°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
h = 1111
Tmin = 0.921, Tmax = 0.988k = 1617
14813 measured reflectionsl = 1313
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.061Hydrogen site location: mixed
wR(F2) = 0.115H atoms treated by a mixture of independent and constrained refinement
S = 0.96 w = 1/[σ2(Fo2) + (0.0345P)2]
where P = (Fo2 + 2Fc2)/3
5436 reflections(Δ/σ)max < 0.001
305 parametersΔρmax = 0.17 e Å3
1 restraintΔρmin = 0.15 e Å3
Crystal data top
C24H25NO3·2CH4OV = 1211.8 (4) Å3
Mr = 439.53Z = 2
Monoclinic, P21Mo Kα radiation
a = 8.894 (2) ŵ = 0.08 mm1
b = 13.7187 (16) ÅT = 293 K
c = 10.680 (2) Å0.30 × 0.30 × 0.15 mm
β = 111.575 (17)°
Data collection top
Bruker–Nonius KappaCCD
diffractometer
5436 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
2610 reflections with I > 2σ(I)
Tmin = 0.921, Tmax = 0.988Rint = 0.116
14813 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0611 restraint
wR(F2) = 0.115H atoms treated by a mixture of independent and constrained refinement
S = 0.96Δρmax = 0.17 e Å3
5436 reflectionsΔρmin = 0.15 e Å3
305 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.4571 (4)0.0371 (2)0.1278 (3)0.0510 (9)
O20.2161 (4)0.4009 (3)0.3492 (4)0.0591 (10)
H2O0.284 (6)0.426 (4)0.307 (5)0.061 (15)*
O30.1944 (4)0.0677 (2)0.0770 (4)0.0660 (10)
O40.0551 (4)1.1537 (3)0.4038 (4)0.0686 (11)
H4O0.058 (7)1.200 (4)0.337 (6)0.09 (2)*
N10.4249 (4)0.4745 (3)0.2281 (4)0.0448 (10)
C10.2616 (5)0.8125 (3)0.3304 (4)0.0390 (10)
C20.1761 (5)0.9019 (3)0.3470 (4)0.0409 (11)
C30.4907 (6)0.2102 (4)0.1807 (5)0.0464 (12)
H30.58710.19980.25300.056*
C40.4297 (5)0.3056 (4)0.1500 (5)0.0450 (12)
C50.4095 (6)0.1326 (3)0.1054 (5)0.0450 (12)
C60.3543 (6)0.6482 (3)0.3954 (5)0.0540 (13)
H60.35560.59360.44750.065*
C70.5309 (5)0.5553 (3)0.3000 (5)0.0532 (14)
H7A0.60290.57190.25350.064*
H7B0.59690.53390.39000.064*
O50.0663 (6)0.3050 (3)0.2485 (5)0.0724 (12)
H5O0.007 (9)0.331 (6)0.259 (8)0.12 (4)*
C80.5275 (5)0.3884 (3)0.2354 (5)0.0519 (13)
H8A0.57660.36710.32830.062*
H8B0.61360.40610.20450.062*
C90.2058 (6)0.2421 (3)0.0333 (5)0.0510 (13)
H90.11020.25290.10630.061*
C100.0835 (6)0.9047 (4)0.4265 (5)0.0532 (13)
H100.07090.84770.46880.064*
C110.2866 (5)0.3213 (3)0.0452 (5)0.0456 (12)
C120.2151 (6)0.4222 (3)0.0158 (5)0.0514 (13)
H12A0.12420.42680.04520.062*
H12B0.17500.43350.08060.062*
C130.3421 (6)0.8087 (3)0.2410 (4)0.0491 (12)
H130.33780.86210.18620.059*
C140.1866 (6)0.9887 (3)0.2849 (6)0.0602 (15)
H140.24640.99060.22950.072*
C150.3377 (6)0.5000 (3)0.0859 (5)0.0527 (14)
H15A0.41420.50690.04110.063*
H15B0.28310.56190.08030.063*
C160.2641 (6)0.1490 (4)0.0050 (5)0.0469 (11)
C170.2690 (6)0.7294 (3)0.4065 (5)0.0542 (14)
H170.21510.72850.46640.065*
C180.4376 (5)0.6453 (3)0.3097 (5)0.0459 (12)
C190.0090 (6)0.9887 (4)0.4456 (5)0.0578 (14)
H190.05020.98770.50150.069*
C200.0220 (6)1.0731 (4)0.3825 (5)0.0522 (13)
C210.4286 (6)0.7268 (3)0.2323 (5)0.0538 (13)
H210.48230.72700.17230.065*
C220.1113 (7)1.0729 (4)0.3026 (6)0.0646 (15)
H220.12161.13000.25940.078*
C230.0516 (7)0.0832 (5)0.1916 (6)0.0864 (19)
H23A0.01250.02190.23460.130*
H23B0.07500.12570.25350.130*
H23C0.02930.11260.16410.130*
C240.3132 (7)0.3394 (4)0.4543 (6)0.0847 (19)
H24A0.25170.31760.50630.127*
H24B0.40620.37490.51120.127*
H24C0.34750.28410.41650.127*
C250.6072 (7)0.0187 (4)0.2328 (6)0.0707 (17)
H25A0.63240.04940.23450.106*
H25B0.60060.03710.31740.106*
H25C0.69030.05610.21790.106*
C260.1413 (7)0.2993 (5)0.1057 (6)0.0846 (19)
H26A0.17240.36340.06940.127*
H26B0.23530.25850.08210.127*
H26C0.06650.27210.06940.127*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.052 (2)0.045 (2)0.058 (2)0.0013 (16)0.0214 (19)0.0015 (16)
O20.045 (2)0.069 (2)0.061 (2)0.0081 (19)0.0175 (19)0.016 (2)
O30.060 (2)0.054 (2)0.067 (3)0.0115 (19)0.004 (2)0.016 (2)
O40.079 (3)0.058 (2)0.085 (3)0.008 (2)0.049 (2)0.005 (3)
N10.039 (2)0.045 (2)0.045 (3)0.0019 (19)0.0086 (18)0.0088 (19)
C10.037 (3)0.045 (3)0.034 (3)0.009 (2)0.012 (2)0.009 (2)
C20.039 (3)0.047 (3)0.035 (3)0.006 (2)0.012 (2)0.004 (2)
C30.042 (3)0.058 (3)0.039 (3)0.004 (3)0.014 (2)0.008 (3)
C40.039 (3)0.051 (3)0.047 (3)0.002 (3)0.019 (2)0.013 (3)
C50.047 (3)0.044 (3)0.049 (3)0.001 (2)0.023 (3)0.005 (2)
C60.067 (3)0.040 (3)0.055 (3)0.004 (3)0.023 (3)0.003 (3)
C70.049 (3)0.048 (3)0.062 (3)0.004 (3)0.020 (3)0.015 (3)
O50.071 (3)0.067 (3)0.075 (3)0.010 (3)0.022 (2)0.001 (2)
C80.042 (3)0.047 (3)0.065 (4)0.003 (2)0.017 (3)0.013 (3)
C90.044 (3)0.054 (3)0.047 (3)0.002 (3)0.007 (2)0.007 (3)
C100.061 (3)0.056 (3)0.051 (3)0.002 (3)0.030 (3)0.011 (3)
C110.043 (3)0.045 (3)0.047 (3)0.002 (2)0.014 (3)0.009 (2)
C120.047 (3)0.050 (3)0.049 (3)0.004 (3)0.009 (2)0.003 (3)
C130.058 (3)0.044 (3)0.048 (3)0.003 (3)0.021 (3)0.001 (2)
C140.070 (4)0.049 (3)0.081 (4)0.005 (3)0.052 (3)0.004 (3)
C150.054 (3)0.052 (3)0.053 (4)0.004 (3)0.020 (3)0.004 (3)
C160.047 (3)0.048 (3)0.047 (3)0.007 (3)0.018 (3)0.010 (3)
C170.070 (3)0.047 (3)0.057 (4)0.007 (3)0.036 (3)0.004 (3)
C180.043 (3)0.045 (3)0.046 (3)0.004 (2)0.012 (2)0.009 (3)
C190.062 (3)0.062 (4)0.063 (4)0.005 (3)0.039 (3)0.001 (3)
C200.049 (3)0.049 (3)0.063 (3)0.003 (3)0.026 (3)0.007 (3)
C210.065 (3)0.047 (3)0.057 (4)0.008 (3)0.032 (3)0.008 (3)
C220.074 (4)0.052 (3)0.089 (4)0.002 (3)0.055 (4)0.007 (3)
C230.074 (4)0.078 (4)0.079 (4)0.017 (3)0.005 (4)0.024 (4)
C240.074 (4)0.100 (5)0.067 (4)0.020 (4)0.010 (3)0.028 (4)
C250.069 (4)0.063 (4)0.068 (4)0.015 (3)0.012 (3)0.002 (3)
C260.078 (4)0.106 (5)0.073 (5)0.022 (4)0.031 (4)0.018 (4)
Geometric parameters (Å, º) top
O1—C51.371 (5)C9—C111.399 (6)
O1—C251.415 (6)C9—H90.9300
O2—C241.415 (6)C10—C191.380 (7)
O2—H2O0.94 (5)C10—H100.9300
O3—C161.367 (6)C11—C121.508 (6)
O3—C231.419 (6)C12—C151.513 (6)
O4—C201.364 (5)C12—H12A0.9700
O4—H4O0.95 (6)C12—H12B0.9700
N1—C151.471 (6)C13—C211.383 (6)
N1—C71.475 (5)C13—H130.9300
N1—C81.477 (5)C14—C221.382 (7)
C1—C171.388 (6)C14—H140.9300
C1—C131.389 (6)C15—H15A0.9700
C1—C21.488 (6)C15—H15B0.9700
C2—C141.383 (6)C17—H170.9300
C2—C101.384 (6)C18—C211.376 (6)
C3—C51.369 (6)C19—C201.366 (6)
C3—C41.409 (6)C19—H190.9300
C3—H30.9300C20—C221.364 (6)
C4—C111.367 (6)C21—H210.9300
C4—C81.516 (6)C22—H220.9300
C5—C161.411 (6)C23—H23A0.9600
C6—C181.373 (6)C23—H23B0.9600
C6—C171.378 (6)C23—H23C0.9600
C6—H60.9300C24—H24A0.9600
C7—C181.511 (6)C24—H24B0.9600
C7—H7A0.9700C24—H24C0.9600
C7—H7B0.9700C25—H25A0.9600
O5—C261.424 (7)C25—H25B0.9600
O5—H5O0.71 (8)C25—H25C0.9600
C8—H8A0.9700C26—H26A0.9600
C8—H8B0.9700C26—H26B0.9600
C9—C161.370 (7)C26—H26C0.9600
C5—O1—C25116.7 (4)C1—C13—H13119.4
C24—O2—H2O107 (3)C22—C14—C2122.1 (5)
C16—O3—C23116.1 (4)C22—C14—H14118.9
C20—O4—H4O107 (3)C2—C14—H14118.9
C15—N1—C7110.6 (4)N1—C15—C12110.7 (4)
C15—N1—C8109.0 (4)N1—C15—H15A109.5
C7—N1—C8108.0 (3)C12—C15—H15A109.5
C17—C1—C13116.5 (4)N1—C15—H15B109.5
C17—C1—C2121.6 (4)C12—C15—H15B109.5
C13—C1—C2121.9 (4)H15A—C15—H15B108.1
C14—C2—C10115.5 (4)O3—C16—C9125.5 (4)
C14—C2—C1121.6 (4)O3—C16—C5115.2 (5)
C10—C2—C1122.8 (4)C9—C16—C5119.3 (5)
C5—C3—C4120.7 (4)C6—C17—C1121.5 (5)
C5—C3—H3119.6C6—C17—H17119.2
C4—C3—H3119.6C1—C17—H17119.2
C11—C4—C3120.0 (4)C6—C18—C21116.7 (5)
C11—C4—C8122.0 (4)C6—C18—C7120.9 (5)
C3—C4—C8118.0 (4)C21—C18—C7122.3 (5)
C3—C5—O1125.4 (5)C20—C19—C10120.2 (5)
C3—C5—C16119.3 (5)C20—C19—H19119.9
O1—C5—C16115.3 (4)C10—C19—H19119.9
C18—C6—C17122.0 (5)C22—C20—O4123.4 (5)
C18—C6—H6119.0C22—C20—C19118.8 (5)
C17—C6—H6119.0O4—C20—C19117.8 (5)
N1—C7—C18112.8 (4)C18—C21—C13122.1 (5)
N1—C7—H7A109.0C18—C21—H21119.0
C18—C7—H7A109.0C13—C21—H21119.0
N1—C7—H7B109.0C20—C22—C14120.7 (5)
C18—C7—H7B109.0C20—C22—H22119.6
H7A—C7—H7B107.8C14—C22—H22119.6
C26—O5—H5O104 (7)O3—C23—H23A109.5
N1—C8—C4111.2 (4)O3—C23—H23B109.5
N1—C8—H8A109.4H23A—C23—H23B109.5
C4—C8—H8A109.4O3—C23—H23C109.5
N1—C8—H8B109.4H23A—C23—H23C109.5
C4—C8—H8B109.4H23B—C23—H23C109.5
H8A—C8—H8B108.0O2—C24—H24A109.5
C16—C9—C11121.5 (5)O2—C24—H24B109.5
C16—C9—H9119.3H24A—C24—H24B109.5
C11—C9—H9119.3O2—C24—H24C109.5
C19—C10—C2122.7 (5)H24A—C24—H24C109.5
C19—C10—H10118.7H24B—C24—H24C109.5
C2—C10—H10118.7O1—C25—H25A109.5
C4—C11—C9119.1 (4)O1—C25—H25B109.5
C4—C11—C12120.6 (4)H25A—C25—H25B109.5
C9—C11—C12120.2 (4)O1—C25—H25C109.5
C11—C12—C15111.8 (4)H25A—C25—H25C109.5
C11—C12—H12A109.2H25B—C25—H25C109.5
C15—C12—H12A109.2O5—C26—H26A109.5
C11—C12—H12B109.2O5—C26—H26B109.5
C15—C12—H12B109.2H26A—C26—H26B109.5
H12A—C12—H12B107.9O5—C26—H26C109.5
C21—C13—C1121.1 (4)H26A—C26—H26C109.5
C21—C13—H13119.4H26B—C26—H26C109.5
C17—C1—C2—C14171.2 (5)C1—C2—C14—C22178.2 (5)
C13—C1—C2—C146.9 (6)C7—N1—C15—C12173.6 (4)
C17—C1—C2—C107.7 (7)C8—N1—C15—C1267.8 (5)
C13—C1—C2—C10174.2 (5)C11—C12—C15—N147.5 (5)
C5—C3—C4—C111.1 (6)C23—O3—C16—C91.4 (7)
C5—C3—C4—C8178.6 (4)C23—O3—C16—C5177.6 (4)
C4—C3—C5—O1179.1 (4)C11—C9—C16—O3179.2 (4)
C4—C3—C5—C160.7 (6)C11—C9—C16—C50.3 (7)
C25—O1—C5—C33.8 (6)C3—C5—C16—O3177.9 (4)
C25—O1—C5—C16176.4 (4)O1—C5—C16—O32.3 (5)
C15—N1—C7—C1865.8 (5)C3—C5—C16—C91.1 (6)
C8—N1—C7—C18175.0 (4)O1—C5—C16—C9178.7 (4)
C15—N1—C8—C453.1 (5)C18—C6—C17—C10.6 (7)
C7—N1—C8—C4173.4 (4)C13—C1—C17—C61.1 (7)
C11—C4—C8—N122.3 (6)C2—C1—C17—C6177.0 (4)
C3—C4—C8—N1158.0 (4)C17—C6—C18—C211.6 (7)
C14—C2—C10—C191.4 (7)C17—C6—C18—C7179.7 (4)
C1—C2—C10—C19177.6 (5)N1—C7—C18—C673.2 (6)
C3—C4—C11—C92.4 (6)N1—C7—C18—C21105.4 (5)
C8—C4—C11—C9177.3 (4)C2—C10—C19—C201.5 (8)
C3—C4—C11—C12176.6 (4)C10—C19—C20—C220.9 (8)
C8—C4—C11—C123.8 (6)C10—C19—C20—O4179.4 (5)
C16—C9—C11—C42.0 (7)C6—C18—C21—C130.9 (7)
C16—C9—C11—C12176.9 (4)C7—C18—C21—C13179.6 (4)
C4—C11—C12—C1515.9 (6)C1—C13—C21—C180.8 (8)
C9—C11—C12—C15165.2 (4)O4—C20—C22—C14180.0 (5)
C17—C1—C13—C211.8 (7)C19—C20—C22—C140.4 (8)
C2—C1—C13—C21176.3 (4)C2—C14—C22—C200.3 (9)
C10—C2—C14—C220.8 (8)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2O···N10.94 (5)1.87 (5)2.812 (5)178 (4)
O4—H4O···O5i0.95 (6)1.71 (6)2.636 (6)165 (5)
O5—H5O···O20.71 (8)2.00 (8)2.684 (6)162 (9)
C15—H15A···O1ii0.972.503.445 (6)164
C23—H23A···O2iii0.962.563.437 (6)152
Symmetry codes: (i) x, y+1, z; (ii) x+1, y+1/2, z; (iii) x, y1/2, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2O···N10.94 (5)1.87 (5)2.812 (5)178 (4)
O4—H4O···O5i0.95 (6)1.71 (6)2.636 (6)165 (5)
O5—H5O···O20.71 (8)2.00 (8)2.684 (6)162 (9)
C15—H15A···O1ii0.972.503.445 (6)164
C23—H23A···O2iii0.962.563.437 (6)152
Symmetry codes: (i) x, y+1, z; (ii) x+1, y+1/2, z; (iii) x, y1/2, z.
 

Footnotes

Crystal structure of 4′-[(6,7-dimeth­oxy-3,4-di­hydro-1H-isoquinolin-2-yl)meth­yl]biphenyl-4-ol methanol disolvate.

Acknowledgements

This work was supported by the Fondazione Cassa di Risparmio di Puglia (FCRP) of Bari (research project: Studio cristallografico di radiotracci­anti PET in valutazione clinica per la diagnosi precoce dell' Alzheimer). The authors thank Mr Giuseppe Chita (Institute of Crystallography CNR, Bari, Italy) for his contribution to the X-ray powder diffraction data collection and Dr Caterina Chiarella (Institute of Crystallography CNR, Bari, Italy) for the technical support to project management.

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Volume 70| Part 11| November 2014| Pages o1149-o1150
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