Inter­play of noncovalent inter­actions in anti­septic quaternary ammonium surfactant Miramistin

The mol­ecular and crystal structure of the widely used anti­septic benzyl­dimeth­yl{3-[(1-oxo­tetra­dec­yl)amino]­prop­yl}ammonium chloride monohydrate (Miramistin, MR), C₂₆H₄₇N₂O⁺·Cl⁻·H₂O, was determined by a single-crystal X-ray diffraction study and analyzed in the framework of the QTAIM (quantum theory of atoms in mol­ecules) approach using both periodic and mol­ecular DFT (density functional theory) calculations. The various noncovalent inter­molecular inter­actions of different strengths were found to be realized in the hydro­philic parts of the crystal packing (i.e. O—H...Cl, N—H...Cl, C—H...Cl, C—H...O and C—H...π). The hydro­phobic parts are built up exclusively by van der Waals H...H contacts. Qu­anti­fication of the inter­action energies using calculated electron-density distribution revealed that the total energy of the contacts within the hydro­philic and hydro­phobic regions are comparable in value. The organic MR cation adopts the bent conformation with the head group tilted back to the long-chain alkyl tail in both the crystalline and the isolated state due to stabilization of this geometry by several intra­molecular C—H...π, C—H...N and H...H inter­actions. This conformation preference is hypothesized to play an important role in the inter­action of MR with biomembranes.

Computing details

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Bruker, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXTL (Bruker, 2012).

Benzyldimethyl{3-[(1-oxotetradecyl)amino]propyl}ammonium chloride monohydrate

Crystal data

C26H47N2O^+·Cl^−·H2O	Dx = 1.127 Mg m^−3
Mr = 457.12	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 6202 reflections
a = 8.8980 (5) Å	θ = 2.5–26.1°
b = 13.0356 (8) Å	µ = 0.17 mm^−1
c = 46.455 (3) Å	T = 120 K
V = 5388.4 (6) Å^3	Prism, colourless
Z = 8	0.32 × 0.26 × 0.08 mm
F(000) = 2016

Data collection

Bruker APEXII CCD diffractometer	4794 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.067
Absorption correction: multi-scan (SADABS; Bruker, 2012)	θmax = 28.0°, θmin = 1.8°
Tmin = 0.912, Tmax = 0.987	h = −11→11
50944 measured reflections	k = −17→17
6501 independent reflections	l = −61→61

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.122	w = 1/[σ^2(Fo^2) + (0.0465P)^2 + 2.8492P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
6501 reflections	Δρmax = 0.56 e Å^−3
295 parameters	Δρmin = −0.24 e Å^−3

Special details

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.12684 (5)	0.16321 (3)	0.21736 (2)	0.02916 (12)
O1	−0.15612 (16)	−0.09545 (11)	0.36654 (3)	0.0371 (3)
N1	−0.23609 (16)	−0.00544 (12)	0.32794 (3)	0.0250 (3)
H1	−0.282 (2)	0.0499 (16)	0.3225 (4)	0.032 (6)*
N2	0.23681 (15)	0.02847 (10)	0.30247 (3)	0.0206 (3)
C1	−0.22748 (19)	−0.02348 (14)	0.35617 (4)	0.0270 (4)
C2	−0.3155 (2)	0.05121 (16)	0.37466 (4)	0.0357 (5)
H2A	−0.4015	0.0146	0.3834	0.043*
H2B	−0.3567	0.1060	0.3622	0.043*
C3	−0.22256 (19)	0.10039 (13)	0.39850 (3)	0.0234 (4)
H3A	−0.1908	0.0469	0.4123	0.028*
H3B	−0.1309	0.1313	0.3901	0.028*
C4	−0.31110 (19)	0.18280 (14)	0.41438 (4)	0.0263 (4)
H4A	−0.3884	0.1491	0.4265	0.032*
H4B	−0.3640	0.2259	0.4001	0.032*
C5	−0.21525 (19)	0.25186 (13)	0.43344 (4)	0.0235 (4)
H5A	−0.1628	0.2090	0.4479	0.028*
H5B	−0.1378	0.2856	0.4214	0.028*
C6	−0.30582 (19)	0.33390 (13)	0.44899 (4)	0.0230 (4)
H6A	−0.3764	0.3001	0.4625	0.028*
H6B	−0.3662	0.3722	0.4347	0.028*
C7	−0.20871 (18)	0.40961 (12)	0.46575 (4)	0.0222 (3)
H7A	−0.1453	0.3709	0.4795	0.027*
H7B	−0.1409	0.4452	0.4521	0.027*
C8	−0.29848 (18)	0.48962 (13)	0.48233 (4)	0.0233 (4)
H8A	−0.3649	0.4541	0.4962	0.028*
H8B	−0.3633	0.5275	0.4687	0.028*
C9	−0.20103 (18)	0.56645 (13)	0.49866 (4)	0.0228 (4)
H9A	−0.1366	0.6033	0.4847	0.027*
H9B	−0.1342	0.5284	0.5119	0.027*
C10	−0.29106 (18)	0.64497 (12)	0.51593 (4)	0.0225 (3)
H10A	−0.3595	0.6820	0.5027	0.027*
H10B	−0.3537	0.6083	0.5302	0.027*
C11	−0.19280 (19)	0.72257 (12)	0.53154 (4)	0.0227 (3)
H11A	−0.1310	0.7595	0.5172	0.027*
H11B	−0.1235	0.6853	0.5445	0.027*
C12	−0.28071 (19)	0.80085 (13)	0.54918 (4)	0.0231 (3)
H12A	−0.3513	0.8376	0.5363	0.028*
H12B	−0.3409	0.7642	0.5639	0.028*
C13	−0.1801 (2)	0.87889 (13)	0.56415 (4)	0.0261 (4)
H13A	−0.1081	0.8419	0.5766	0.031*
H13B	−0.1213	0.9162	0.5494	0.031*
C14	−0.2656 (2)	0.95655 (15)	0.58235 (4)	0.0358 (4)
H14A	−0.1946	1.0053	0.5909	0.054*
H14B	−0.3200	0.9207	0.5977	0.054*
H14C	−0.3373	0.9937	0.5702	0.054*
C15	−0.17352 (19)	−0.07153 (14)	0.30586 (4)	0.0255 (4)
H15A	−0.2509	−0.0846	0.2910	0.031*
H15B	−0.1459	−0.1382	0.3146	0.031*
C16	−0.03452 (19)	−0.02447 (13)	0.29156 (4)	0.0242 (4)
H16A	−0.0057	−0.0656	0.2745	0.029*
H16B	−0.0574	0.0462	0.2851	0.029*
C17	0.09383 (18)	−0.02249 (13)	0.31294 (3)	0.0212 (3)
H17A	0.1177	−0.0940	0.3185	0.025*
H17B	0.0595	0.0136	0.3305	0.025*
C18	0.35839 (19)	0.00420 (13)	0.32380 (4)	0.0260 (4)
H18A	0.3778	−0.0698	0.3238	0.039*
H18B	0.3264	0.0256	0.3431	0.039*
H18C	0.4504	0.0409	0.3185	0.039*
C19	0.2847 (2)	−0.01383 (14)	0.27381 (4)	0.0294 (4)
H19A	0.2827	−0.0890	0.2745	0.044*
H19B	0.3869	0.0095	0.2694	0.044*
H19C	0.2157	0.0104	0.2588	0.044*
C20	0.22035 (19)	0.14464 (12)	0.29902 (3)	0.0225 (3)
H20A	0.3146	0.1723	0.2908	0.027*
H20B	0.1387	0.1585	0.2851	0.027*
C21	0.1866 (2)	0.20083 (12)	0.32645 (4)	0.0228 (3)
C22	0.3036 (2)	0.23497 (13)	0.34411 (4)	0.0270 (4)
H22A	0.4047	0.2210	0.3389	0.032*
C23	0.2741 (2)	0.28896 (14)	0.36918 (4)	0.0332 (4)
H23A	0.3544	0.3113	0.3811	0.040*
C24	0.1265 (2)	0.31010 (14)	0.37674 (4)	0.0354 (5)
H24A	0.1058	0.3463	0.3940	0.042*
C25	0.0091 (2)	0.27881 (13)	0.35922 (4)	0.0326 (4)
H25A	−0.0916	0.2946	0.3644	0.039*
C26	0.0386 (2)	0.22432 (13)	0.33408 (4)	0.0271 (4)
H26A	−0.0421	0.2030	0.3221	0.032*
O1W	0.42458 (19)	0.29093 (12)	0.23810 (4)	0.0429 (4)
H1W	0.471 (3)	0.2569 (17)	0.2509 (5)	0.044 (7)*
H2W	0.352 (3)	0.254 (2)	0.2332 (6)	0.066 (9)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0264 (2)	0.0268 (2)	0.0343 (2)	0.00094 (17)	−0.00069 (18)	−0.00165 (18)
O1	0.0445 (8)	0.0400 (8)	0.0269 (7)	0.0031 (7)	−0.0014 (6)	−0.0009 (6)
N1	0.0204 (7)	0.0253 (8)	0.0292 (8)	0.0032 (6)	−0.0002 (6)	−0.0056 (6)
N2	0.0216 (7)	0.0207 (7)	0.0193 (7)	0.0035 (6)	0.0004 (5)	0.0013 (5)
C1	0.0214 (8)	0.0301 (9)	0.0296 (9)	−0.0048 (7)	−0.0004 (7)	−0.0091 (8)
C2	0.0251 (9)	0.0475 (12)	0.0344 (10)	0.0001 (8)	0.0009 (8)	−0.0176 (9)
C3	0.0258 (9)	0.0240 (8)	0.0205 (8)	−0.0033 (7)	0.0018 (7)	−0.0031 (7)
C4	0.0232 (9)	0.0305 (9)	0.0253 (9)	−0.0020 (7)	0.0013 (7)	−0.0076 (7)
C5	0.0218 (8)	0.0252 (8)	0.0237 (8)	−0.0021 (7)	0.0012 (7)	−0.0052 (7)
C6	0.0214 (8)	0.0244 (8)	0.0234 (8)	0.0008 (7)	0.0006 (6)	−0.0046 (7)
C7	0.0200 (8)	0.0220 (8)	0.0244 (8)	0.0014 (7)	0.0008 (6)	−0.0052 (7)
C8	0.0214 (8)	0.0231 (8)	0.0254 (9)	0.0013 (7)	−0.0004 (7)	−0.0041 (7)
C9	0.0208 (8)	0.0227 (8)	0.0250 (9)	0.0014 (7)	−0.0001 (7)	−0.0046 (7)
C10	0.0209 (8)	0.0214 (8)	0.0252 (9)	0.0018 (6)	−0.0004 (7)	−0.0033 (7)
C11	0.0210 (8)	0.0216 (8)	0.0255 (9)	−0.0009 (6)	0.0013 (7)	−0.0038 (7)
C12	0.0218 (8)	0.0236 (8)	0.0241 (8)	0.0021 (7)	0.0005 (7)	−0.0036 (7)
C13	0.0268 (9)	0.0240 (9)	0.0275 (9)	−0.0003 (7)	0.0013 (7)	−0.0050 (7)
C14	0.0398 (11)	0.0300 (10)	0.0377 (11)	0.0020 (9)	0.0011 (9)	−0.0109 (8)
C15	0.0245 (9)	0.0274 (9)	0.0247 (9)	−0.0022 (7)	−0.0023 (7)	−0.0057 (7)
C16	0.0244 (9)	0.0275 (9)	0.0206 (8)	0.0008 (7)	−0.0017 (7)	−0.0012 (7)
C17	0.0210 (8)	0.0210 (8)	0.0215 (8)	−0.0005 (6)	0.0003 (6)	0.0025 (6)
C18	0.0228 (9)	0.0259 (9)	0.0292 (9)	0.0039 (7)	−0.0038 (7)	0.0047 (7)
C19	0.0334 (10)	0.0296 (9)	0.0252 (9)	0.0045 (8)	0.0072 (8)	−0.0036 (7)
C20	0.0250 (9)	0.0196 (8)	0.0228 (8)	0.0018 (7)	0.0015 (7)	0.0040 (6)
C21	0.0283 (9)	0.0175 (8)	0.0224 (8)	−0.0002 (7)	0.0025 (7)	0.0045 (6)
C22	0.0318 (10)	0.0212 (8)	0.0280 (9)	0.0000 (7)	−0.0004 (7)	0.0048 (7)
C23	0.0481 (12)	0.0252 (9)	0.0263 (9)	−0.0044 (8)	−0.0035 (9)	0.0021 (8)
C24	0.0582 (13)	0.0239 (9)	0.0240 (9)	−0.0018 (9)	0.0092 (9)	−0.0009 (7)
C25	0.0415 (11)	0.0214 (9)	0.0348 (10)	0.0008 (8)	0.0152 (9)	0.0037 (7)
C26	0.0290 (9)	0.0199 (8)	0.0322 (9)	−0.0022 (7)	0.0042 (8)	0.0033 (7)
O1W	0.0444 (9)	0.0361 (8)	0.0481 (9)	−0.0032 (7)	−0.0182 (8)	0.0076 (7)

Geometric parameters (Å, º)

O1—C1	1.231 (2)	C12—C13	1.523 (2)
N1—C1	1.335 (2)	C12—H12A	0.9900
N1—C15	1.451 (2)	C12—H12B	0.9900
N1—H1	0.87 (2)	C13—C14	1.523 (2)
N2—C18	1.501 (2)	C13—H13A	0.9900
N2—C19	1.503 (2)	C13—H13B	0.9900
N2—C17	1.515 (2)	C14—H14A	0.9800
N2—C20	1.530 (2)	C14—H14B	0.9800
C1—C2	1.516 (2)	C14—H14C	0.9800
C2—C3	1.524 (2)	C15—C16	1.532 (2)
C2—H2A	0.9900	C15—H15A	0.9900
C2—H2B	0.9900	C15—H15B	0.9900
C3—C4	1.523 (2)	C16—C17	1.514 (2)
C3—H3A	0.9900	C16—H16A	0.9900
C3—H3B	0.9900	C16—H16B	0.9900
C4—C5	1.524 (2)	C17—H17A	0.9900
C4—H4A	0.9900	C17—H17B	0.9900
C4—H4B	0.9900	C18—H18A	0.9800
C5—C6	1.521 (2)	C18—H18B	0.9800
C5—H5A	0.9900	C18—H18C	0.9800
C5—H5B	0.9900	C19—H19A	0.9800
C6—C7	1.525 (2)	C19—H19B	0.9800
C6—H6A	0.9900	C19—H19C	0.9800
C6—H6B	0.9900	C20—C21	1.500 (2)
C7—C8	1.523 (2)	C20—H20A	0.9900
C7—H7A	0.9900	C20—H20B	0.9900
C7—H7B	0.9900	C21—C22	1.398 (2)
C8—C9	1.526 (2)	C21—C26	1.398 (2)
C8—H8A	0.9900	C22—C23	1.386 (2)
C8—H8B	0.9900	C22—H22A	0.9500
C9—C10	1.527 (2)	C23—C24	1.387 (3)
C9—H9A	0.9900	C23—H23A	0.9500
C9—H9B	0.9900	C24—C25	1.386 (3)
C10—C11	1.521 (2)	C24—H24A	0.9500
C10—H10A	0.9900	C25—C26	1.392 (3)
C10—H10B	0.9900	C25—H25A	0.9500
C11—C12	1.525 (2)	C26—H26A	0.9500
C11—H11A	0.9900	O1W—H1W	0.85 (2)
C11—H11B	0.9900	O1W—H2W	0.84 (3)
C1—N1—C15	124.62 (16)	C13—C12—H12A	109.0
C1—N1—H1	117.6 (13)	C11—C12—H12A	109.0
C15—N1—H1	117.8 (13)	C13—C12—H12B	109.0
C18—N2—C19	107.66 (13)	C11—C12—H12B	109.0
C18—N2—C17	107.50 (12)	H12A—C12—H12B	107.8
C19—N2—C17	111.21 (13)	C14—C13—C12	113.80 (15)
C18—N2—C20	110.28 (13)	C14—C13—H13A	108.8
C19—N2—C20	107.32 (12)	C12—C13—H13A	108.8
C17—N2—C20	112.77 (12)	C14—C13—H13B	108.8
O1—C1—N1	123.26 (16)	C12—C13—H13B	108.8
O1—C1—C2	122.30 (17)	H13A—C13—H13B	107.7
N1—C1—C2	114.44 (16)	C13—C14—H14A	109.5
C1—C2—C3	113.65 (15)	C13—C14—H14B	109.5
C1—C2—H2A	108.8	H14A—C14—H14B	109.5
C3—C2—H2A	108.8	C13—C14—H14C	109.5
C1—C2—H2B	108.8	H14A—C14—H14C	109.5
C3—C2—H2B	108.8	H14B—C14—H14C	109.5
H2A—C2—H2B	107.7	N1—C15—C16	112.24 (14)
C4—C3—C2	111.59 (14)	N1—C15—H15A	109.2
C4—C3—H3A	109.3	C16—C15—H15A	109.2
C2—C3—H3A	109.3	N1—C15—H15B	109.2
C4—C3—H3B	109.3	C16—C15—H15B	109.2
C2—C3—H3B	109.3	H15A—C15—H15B	107.9
H3A—C3—H3B	108.0	C17—C16—C15	109.36 (13)
C3—C4—C5	114.12 (14)	C17—C16—H16A	109.8
C3—C4—H4A	108.7	C15—C16—H16A	109.8
C5—C4—H4A	108.7	C17—C16—H16B	109.8
C3—C4—H4B	108.7	C15—C16—H16B	109.8
C5—C4—H4B	108.7	H16A—C16—H16B	108.3
H4A—C4—H4B	107.6	C16—C17—N2	115.48 (13)
C6—C5—C4	113.24 (14)	C16—C17—H17A	108.4
C6—C5—H5A	108.9	N2—C17—H17A	108.4
C4—C5—H5A	108.9	C16—C17—H17B	108.4
C6—C5—H5B	108.9	N2—C17—H17B	108.4
C4—C5—H5B	108.9	H17A—C17—H17B	107.5
H5A—C5—H5B	107.7	N2—C18—H18A	109.5
C5—C6—C7	113.39 (14)	N2—C18—H18B	109.5
C5—C6—H6A	108.9	H18A—C18—H18B	109.5
C7—C6—H6A	108.9	N2—C18—H18C	109.5
C5—C6—H6B	108.9	H18A—C18—H18C	109.5
C7—C6—H6B	108.9	H18B—C18—H18C	109.5
H6A—C6—H6B	107.7	N2—C19—H19A	109.5
C8—C7—C6	113.84 (13)	N2—C19—H19B	109.5
C8—C7—H7A	108.8	H19A—C19—H19B	109.5
C6—C7—H7A	108.8	N2—C19—H19C	109.5
C8—C7—H7B	108.8	H19A—C19—H19C	109.5
C6—C7—H7B	108.8	H19B—C19—H19C	109.5
H7A—C7—H7B	107.7	C21—C20—N2	114.44 (13)
C7—C8—C9	113.75 (14)	C21—C20—H20A	108.7
C7—C8—H8A	108.8	N2—C20—H20A	108.7
C9—C8—H8A	108.8	C21—C20—H20B	108.7
C7—C8—H8B	108.8	N2—C20—H20B	108.7
C9—C8—H8B	108.8	H20A—C20—H20B	107.6
H8A—C8—H8B	107.7	C22—C21—C26	118.88 (16)
C8—C9—C10	113.74 (13)	C22—C21—C20	120.33 (16)
C8—C9—H9A	108.8	C26—C21—C20	120.72 (16)
C10—C9—H9A	108.8	C23—C22—C21	120.94 (18)
C8—C9—H9B	108.8	C23—C22—H22A	119.5
C10—C9—H9B	108.8	C21—C22—H22A	119.5
H9A—C9—H9B	107.7	C22—C23—C24	119.53 (18)
C11—C10—C9	113.24 (14)	C22—C23—H23A	120.2
C11—C10—H10A	108.9	C24—C23—H23A	120.2
C9—C10—H10A	108.9	C25—C24—C23	120.43 (17)
C11—C10—H10B	108.9	C25—C24—H24A	119.8
C9—C10—H10B	108.9	C23—C24—H24A	119.8
H10A—C10—H10B	107.7	C24—C25—C26	120.06 (18)
C10—C11—C12	113.98 (14)	C24—C25—H25A	120.0
C10—C11—H11A	108.8	C26—C25—H25A	120.0
C12—C11—H11A	108.8	C25—C26—C21	120.14 (18)
C10—C11—H11B	108.8	C25—C26—H26A	119.9
C12—C11—H11B	108.8	C21—C26—H26A	119.9
H11A—C11—H11B	107.7	H1W—O1W—H2W	105 (2)
C13—C12—C11	112.99 (14)
C15—N1—C1—O1	5.0 (3)	C15—C16—C17—N2	−176.22 (13)
C15—N1—C1—C2	−173.97 (15)	C18—N2—C17—C16	−168.65 (14)
O1—C1—C2—C3	53.7 (2)	C19—N2—C17—C16	−51.03 (18)
N1—C1—C2—C3	−127.30 (17)	C20—N2—C17—C16	69.58 (18)
C1—C2—C3—C4	173.97 (16)	C18—N2—C20—C21	−57.63 (18)
C2—C3—C4—C5	−166.28 (16)	C19—N2—C20—C21	−174.63 (14)
C3—C4—C5—C6	179.74 (14)	C17—N2—C20—C21	62.56 (18)
C4—C5—C6—C7	−174.34 (14)	N2—C20—C21—C22	88.08 (19)
C5—C6—C7—C8	−177.77 (14)	N2—C20—C21—C26	−95.07 (18)
C6—C7—C8—C9	−178.97 (14)	C26—C21—C22—C23	1.6 (2)
C7—C8—C9—C10	−178.48 (14)	C20—C21—C22—C23	178.54 (15)
C8—C9—C10—C11	−178.69 (14)	C21—C22—C23—C24	−0.5 (3)
C9—C10—C11—C12	−179.35 (14)	C22—C23—C24—C25	−0.9 (3)
C10—C11—C12—C13	−178.92 (14)	C23—C24—C25—C26	1.1 (3)
C11—C12—C13—C14	−178.88 (15)	C24—C25—C26—C21	0.1 (3)
C1—N1—C15—C16	−107.98 (19)	C22—C21—C26—C25	−1.4 (2)
N1—C15—C16—C17	69.21 (18)	C20—C21—C26—C25	−178.32 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···Cl1^i	0.87 (2)	2.50 (2)	3.2786 (16)	149.3 (16)
O1W—H1W···Cl1^ii	0.85 (2)	2.36 (2)	3.2081 (19)	173 (2)
O1W—H2W···Cl1	0.84 (3)	2.44 (3)	3.2740 (18)	174 (3)

Symmetry codes: (i) x−1/2, y, −z+1/2; (ii) x+1/2, y, −z+1/2.