In the title compound, 3-[(3,4-dihydro-2-methyl-4-oxopyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)-4-methylthiazolium hexafluorophosphate monohydrate, C
12H
16N
3O
2S
+·PF
6-·H
2O, oxythiamine is a monovalent cation with a neutral oxopyrimidine ring. The molecule assumes the
F conformation, which is a common form for thiamine but which is substantially different from the unusual
V conformation found in the chloride and hydrochloride salts of oxythiamine. The anion-bridging interaction, C-H
anion
pyrimidine, is emphasized as being important for stabilization of the
F conformation.
Supporting information
CCDC reference: 152640
Aqueous solutions of oxythiamine chloride hydrochloride (Sigma Chemical Co.; 169.2 mg, 0.5 mmol) and NH4PF6 (Kanto Chemical Co.; 407.5 mg, 2.5 mmol) were mixed (pH 2). The pH value was adjusted to 7 using a 1 N NaOH solution. Crystals of (I) were obtained from the resulting solution after several days.
All H atoms were located from difference Fourier maps and refined isotropically, except for the H atoms of water (HW1 and HW2) which were fixed in the refinements with an isotropic displacement parameter of 0.06 Å2.
Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1985); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: MSC/AFC Diffractometer Control Software; program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.
3-[(3,4-dihydro-2-methyl-4-oxopyrimidin-5-yl)methyl]- 5-(2-hydroxyethyl)-4-methylthiazolium hexafluorophosphate monohydrate
top
Crystal data top
C12H16N3O2S+·PF6−·H2O | Z = 2 |
Mr = 429.32 | F(000) = 440 |
Triclinic, P1 | Dx = 1.586 Mg m−3 |
a = 9.2881 (12) Å | Mo Kα radiation, λ = 0.71069 Å |
b = 11.9318 (13) Å | Cell parameters from 24 reflections |
c = 8.8201 (7) Å | θ = 14.9–15.0° |
α = 91.607 (8)° | µ = 0.35 mm−1 |
β = 92.081 (9)° | T = 293 K |
γ = 112.925 (9)° | Tabular, colourless |
V = 898.73 (17) Å3 | 0.40 × 0.35 × 0.15 mm |
Data collection top
Rigaku AFC-7R diffractometer | Rint = 0.005 |
Radiation source: rotating anode | θmax = 27.5°, θmin = 2.9° |
Graphite monochromator | h = −2→12 |
ω/2θ scans | k = −15→14 |
4485 measured reflections | l = −11→11 |
4133 independent reflections | 3 standard reflections every 150 reflections |
3430 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.051 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.154 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0794P)2 + 0.523P] where P(Fo2 + 2Fc2)/3 |
4133 reflections | (Δ/σ)max = 0.004 |
299 parameters | Δρmax = 0.59 e Å−3 |
2 restraints | Δρmin = −0.37 e Å−3 |
Crystal data top
C12H16N3O2S+·PF6−·H2O | γ = 112.925 (9)° |
Mr = 429.32 | V = 898.73 (17) Å3 |
Triclinic, P1 | Z = 2 |
a = 9.2881 (12) Å | Mo Kα radiation |
b = 11.9318 (13) Å | µ = 0.35 mm−1 |
c = 8.8201 (7) Å | T = 293 K |
α = 91.607 (8)° | 0.40 × 0.35 × 0.15 mm |
β = 92.081 (9)° | |
Data collection top
Rigaku AFC-7R diffractometer | Rint = 0.005 |
4485 measured reflections | 3 standard reflections every 150 reflections |
4133 independent reflections | intensity decay: none |
3430 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.051 | 2 restraints |
wR(F2) = 0.154 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | Δρmax = 0.59 e Å−3 |
4133 reflections | Δρmin = −0.37 e Å−3 |
299 parameters | |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
S1 | 0.40635 (8) | 0.86132 (6) | 0.15537 (8) | 0.0537 (2) | |
C2 | 0.4008 (3) | 0.9916 (2) | 0.2232 (3) | 0.0474 (5) | |
N3 | 0.2572 (2) | 0.98628 (16) | 0.2318 (2) | 0.0400 (4) | |
C4 | 0.1420 (3) | 0.8743 (2) | 0.1806 (3) | 0.0425 (5) | |
C5 | 0.2047 (3) | 0.7949 (2) | 0.1374 (3) | 0.0456 (5) | |
C41 | −0.0269 (3) | 0.8550 (3) | 0.1793 (4) | 0.0615 (7) | |
C51 | 0.1207 (4) | 0.6631 (2) | 0.0881 (3) | 0.0543 (6) | |
C52 | 0.1507 (4) | 0.5807 (2) | 0.2025 (3) | 0.0554 (6) | |
O53 | 0.3078 (3) | 0.59020 (19) | 0.1953 (2) | 0.0616 (5) | |
C35' | 0.2172 (3) | 1.0846 (2) | 0.3007 (3) | 0.0463 (5) | |
N1' | 0.5453 (2) | 1.34237 (19) | 0.5172 (2) | 0.0487 (5) | |
C2' | 0.6023 (3) | 1.4149 (2) | 0.4062 (3) | 0.0434 (5) | |
N3' | 0.5424 (2) | 1.38797 (16) | 0.2621 (2) | 0.0425 (4) | |
C4' | 0.4204 (3) | 1.27990 (19) | 0.2150 (3) | 0.0417 (5) | |
C5' | 0.3573 (3) | 1.20005 (19) | 0.3367 (3) | 0.0410 (5) | |
C6' | 0.4216 (3) | 1.2356 (2) | 0.4789 (3) | 0.0473 (5) | |
C2'1 | 0.7412 (4) | 1.5313 (3) | 0.4354 (4) | 0.0583 (7) | |
O4'1 | 0.3731 (2) | 1.25819 (16) | 0.0813 (2) | 0.0576 (5) | |
P1 | 0.84895 (8) | 1.18195 (6) | 0.34821 (7) | 0.04941 (19) | |
F1 | 0.9845 (3) | 1.2331 (3) | 0.2361 (3) | 0.1013 (8) | |
F2 | 0.9592 (3) | 1.1428 (4) | 0.4530 (3) | 0.1376 (13) | |
F3 | 0.7109 (3) | 1.1293 (3) | 0.4597 (3) | 0.1057 (9) | |
F4 | 0.7331 (2) | 1.2172 (2) | 0.2428 (3) | 0.0892 (7) | |
F5 | 0.7868 (4) | 1.0553 (3) | 0.2631 (5) | 0.1556 (14) | |
F6 | 0.9051 (4) | 1.3075 (3) | 0.4328 (5) | 0.1571 (15) | |
OW | 0.3090 (2) | 0.44654 (16) | −0.0501 (2) | 0.0521 (4) | |
H2 | 0.491 (3) | 1.057 (3) | 0.260 (3) | 0.051 (7)* | |
H41A | −0.091 (5) | 0.783 (4) | 0.130 (5) | 0.095 (13)* | |
H41B | −0.042 (5) | 0.914 (4) | 0.124 (5) | 0.107 (15)* | |
H41C | −0.064 (6) | 0.858 (4) | 0.286 (6) | 0.125 (17)* | |
H51A | 0.008 (4) | 0.649 (3) | 0.068 (4) | 0.072 (10)* | |
H51B | 0.154 (4) | 0.649 (3) | 0.002 (4) | 0.062 (9)* | |
H52A | 0.082 (4) | 0.497 (3) | 0.179 (3) | 0.060 (8)* | |
H52B | 0.130 (3) | 0.597 (3) | 0.309 (4) | 0.055 (8)* | |
H53 | 0.359 (5) | 0.608 (4) | 0.279 (3) | 0.113 (16)* | |
H351 | 0.145 (3) | 1.102 (3) | 0.225 (3) | 0.053 (7)* | |
H352 | 0.162 (4) | 1.052 (3) | 0.395 (4) | 0.067 (9)* | |
H3' | 0.585 (3) | 1.441 (3) | 0.194 (3) | 0.048 (7)* | |
H6' | 0.376 (3) | 1.178 (3) | 0.569 (3) | 0.055 (8)* | |
H2'1 | 0.735 (5) | 1.592 (4) | 0.372 (5) | 0.084 (11)* | |
H2'2 | 0.741 (5) | 1.557 (4) | 0.534 (6) | 0.115 (16)* | |
H2'3 | 0.819 (3) | 1.526 (4) | 0.407 (5) | 0.097 (15)* | |
HW1 | 0.3056 | 0.4959 | 0.0472 | 0.060* | |
HW2 | 0.3400 | 0.3893 | −0.0254 | 0.060* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.0477 (3) | 0.0420 (3) | 0.0677 (4) | 0.0144 (3) | 0.0025 (3) | −0.0062 (3) |
C2 | 0.0390 (11) | 0.0346 (10) | 0.0611 (14) | 0.0070 (9) | −0.0016 (10) | −0.0008 (10) |
N3 | 0.0389 (9) | 0.0315 (8) | 0.0444 (10) | 0.0084 (7) | −0.0035 (7) | 0.0030 (7) |
C4 | 0.0411 (11) | 0.0370 (10) | 0.0403 (11) | 0.0062 (9) | −0.0077 (8) | 0.0028 (8) |
C5 | 0.0495 (12) | 0.0387 (11) | 0.0401 (11) | 0.0092 (9) | −0.0081 (9) | −0.0020 (9) |
C41 | 0.0410 (13) | 0.0512 (15) | 0.082 (2) | 0.0091 (11) | −0.0146 (13) | −0.0047 (14) |
C51 | 0.0619 (16) | 0.0415 (12) | 0.0495 (14) | 0.0118 (11) | −0.0150 (12) | −0.0116 (10) |
C52 | 0.0651 (16) | 0.0377 (12) | 0.0509 (14) | 0.0073 (11) | −0.0026 (12) | −0.0055 (10) |
O53 | 0.0734 (13) | 0.0608 (11) | 0.0493 (10) | 0.0266 (10) | −0.0097 (9) | −0.0098 (9) |
C35' | 0.0409 (11) | 0.0353 (10) | 0.0600 (14) | 0.0123 (9) | 0.0006 (10) | 0.0009 (10) |
N1' | 0.0517 (11) | 0.0451 (10) | 0.0426 (10) | 0.0127 (9) | −0.0052 (8) | −0.0010 (8) |
C2' | 0.0443 (11) | 0.0357 (10) | 0.0488 (12) | 0.0149 (9) | −0.0035 (9) | −0.0028 (9) |
N3' | 0.0479 (10) | 0.0311 (9) | 0.0439 (10) | 0.0106 (8) | −0.0005 (8) | 0.0033 (8) |
C4' | 0.0466 (12) | 0.0314 (10) | 0.0448 (11) | 0.0135 (9) | −0.0038 (9) | −0.0007 (8) |
C5' | 0.0407 (11) | 0.0315 (10) | 0.0490 (12) | 0.0123 (8) | −0.0009 (9) | 0.0026 (8) |
C6' | 0.0491 (13) | 0.0427 (11) | 0.0465 (12) | 0.0137 (10) | 0.0016 (10) | 0.0051 (9) |
C2'1 | 0.0519 (15) | 0.0437 (13) | 0.0664 (18) | 0.0058 (12) | −0.0071 (13) | −0.0032 (12) |
O4'1 | 0.0749 (12) | 0.0423 (9) | 0.0457 (9) | 0.0137 (8) | −0.0106 (8) | −0.0007 (7) |
P1 | 0.0449 (3) | 0.0563 (4) | 0.0490 (4) | 0.0214 (3) | 0.0033 (3) | 0.0073 (3) |
F1 | 0.0755 (13) | 0.142 (2) | 0.1048 (17) | 0.0558 (14) | 0.0417 (12) | 0.0579 (15) |
F2 | 0.1020 (18) | 0.255 (4) | 0.1028 (18) | 0.113 (2) | 0.0262 (14) | 0.088 (2) |
F3 | 0.0731 (13) | 0.173 (3) | 0.0805 (14) | 0.0529 (15) | 0.0292 (11) | 0.0524 (15) |
F4 | 0.0659 (11) | 0.1194 (17) | 0.0904 (14) | 0.0425 (12) | 0.0035 (10) | 0.0423 (13) |
F5 | 0.168 (3) | 0.0786 (17) | 0.210 (4) | 0.0412 (19) | 0.015 (3) | −0.048 (2) |
F6 | 0.0992 (19) | 0.128 (2) | 0.211 (4) | 0.0171 (17) | −0.011 (2) | −0.097 (2) |
OW | 0.0600 (10) | 0.0457 (9) | 0.0459 (9) | 0.0158 (8) | −0.0018 (8) | 0.0044 (7) |
Geometric parameters (Å, º) top
S1—C2 | 1.670 (2) | N1'—C2' | 1.310 (3) |
S1—C5 | 1.725 (2) | N1'—C6' | 1.366 (3) |
C2—N3 | 1.316 (3) | C2'—N3' | 1.347 (3) |
C2—H2 | 0.94 (3) | C2'—C2'1 | 1.490 (3) |
N3—C4 | 1.397 (3) | N3'—C4' | 1.384 (3) |
N3—C35' | 1.482 (3) | N3'—H3' | 0.88 (3) |
C4—C5 | 1.345 (4) | C4'—O4'1 | 1.228 (3) |
C4—C41 | 1.493 (4) | C4'—C5' | 1.439 (3) |
C5—C51 | 1.500 (3) | C5'—C6' | 1.352 (3) |
C41—H41A | 0.91 (4) | C6'—H6' | 1.05 (3) |
C41—H41B | 0.92 (5) | C2'1—H2'1 | 0.94 (4) |
C41—H41C | 1.02 (5) | C2'1—H2'2 | 0.92 (5) |
C51—C52 | 1.520 (4) | C2'1—H2'3 | 0.798 (19) |
C51—H51A | 1.00 (4) | P1—F6 | 1.541 (3) |
C51—H51B | 0.87 (3) | P1—F5 | 1.551 (3) |
C52—O53 | 1.423 (4) | P1—F2 | 1.565 (2) |
C52—H52A | 0.96 (3) | P1—F1 | 1.569 (2) |
C52—H52B | 0.99 (3) | P1—F4 | 1.5819 (19) |
O53—H53 | 0.840 (19) | P1—F3 | 1.583 (2) |
C35'—C5' | 1.497 (3) | OW—HW1 | 1.0359 |
C35'—H351 | 1.01 (3) | OW—HW2 | 0.8683 |
C35'—H352 | 1.00 (3) | | |
| | | |
S1···O53 | 3.034 (2) | C2···F3i | 3.202 (3) |
N1'···F3 | 3.481 (3) | N3···F3i | 3.140 (3) |
C6'···F3 | 3.396 (4) | C4···F3i | 3.417 (3) |
C2'···F4 | 3.360 (3) | C4···F2i | 3.388 (3) |
N3'···F4 | 3.183 (3) | S1···F4ii | 3.664 (2) |
C4'···F4 | 3.272 (3) | C5···F4ii | 3.431 (3) |
| | | |
C2—S1—C5 | 91.04 (12) | C2'—N1'—C6' | 116.3 (2) |
N3—C2—S1 | 112.72 (17) | N1'—C2'—N3' | 122.6 (2) |
N3—C2—H2 | 124.9 (17) | N1'—C2'—C2'1 | 120.3 (2) |
S1—C2—H2 | 122.1 (17) | N3'—C2'—C2'1 | 117.1 (2) |
C2—N3—C4 | 113.7 (2) | C2'—N3'—C4' | 123.9 (2) |
C2—N3—C35' | 124.18 (19) | C2'—N3'—H3' | 118.0 (19) |
C4—N3—C35' | 121.89 (19) | C4'—N3'—H3' | 118.0 (18) |
C5—C4—N3 | 111.6 (2) | O4'1—C4'—N3' | 121.4 (2) |
C5—C4—C41 | 128.2 (2) | O4'1—C4'—C5' | 125.1 (2) |
N3—C4—C41 | 120.2 (2) | N3'—C4'—C5' | 113.51 (19) |
C4—C5—C51 | 127.9 (2) | C6'—C5'—C4' | 118.7 (2) |
C4—C5—S1 | 110.86 (16) | C6'—C5'—C35' | 123.1 (2) |
C51—C5—S1 | 121.1 (2) | C4'—C5'—C35' | 118.1 (2) |
C4—C41—H41A | 113 (3) | C5'—C6'—N1' | 124.9 (2) |
C4—C41—H41B | 109 (3) | C5'—C6'—H6' | 119.3 (16) |
H41A—C41—H41B | 104 (4) | N1'—C6'—H6' | 115.9 (16) |
C4—C41—H41C | 112 (3) | C2'—C2'1—H2'1 | 111 (2) |
H41A—C41—H41C | 109 (4) | C2'—C2'1—H2'2 | 108 (3) |
H41B—C41—H41C | 109 (4) | H2'1—C2'1—H2'2 | 108 (4) |
C5—C51—C52 | 111.3 (2) | C2'—C2'1—H2'3 | 111 (3) |
C5—C51—H51A | 107 (2) | H2'1—C2'1—H2'3 | 100 (4) |
C52—C51—H51A | 115 (2) | H2'2—C2'1—H2'3 | 119 (4) |
C5—C51—H51B | 110 (2) | F6—P1—F5 | 178.12 (19) |
C52—C51—H51B | 107 (2) | F6—P1—F2 | 91.3 (2) |
H51A—C51—H51B | 106 (3) | F5—P1—F2 | 90.1 (2) |
O53—C52—C51 | 109.4 (2) | F6—P1—F1 | 90.27 (19) |
O53—C52—H52A | 108.1 (18) | F5—P1—F1 | 91.04 (19) |
C51—C52—H52A | 110.3 (18) | F2—P1—F1 | 89.02 (13) |
O53—C52—H52B | 109.7 (17) | F6—P1—F4 | 90.13 (19) |
C51—C52—H52B | 114.5 (17) | F5—P1—F4 | 88.5 (2) |
H52A—C52—H52B | 105 (2) | F2—P1—F4 | 178.11 (16) |
C52—O53—H53 | 114 (3) | F1—P1—F4 | 92.26 (12) |
N3—C35'—C5' | 113.17 (19) | F6—P1—F3 | 90.30 (19) |
N3—C35'—H351 | 107.4 (16) | F5—P1—F3 | 88.4 (2) |
C5'—C35'—H351 | 108.3 (16) | F2—P1—F3 | 91.34 (13) |
N3—C35'—H352 | 106.3 (19) | F1—P1—F3 | 179.32 (16) |
C5'—C35'—H352 | 110.9 (19) | F4—P1—F3 | 87.37 (12) |
H351—C35'—H352 | 111 (3) | HW1—OW—HW2 | 109.1 |
| | | |
C5'—C35'—N3—C2 | 9.7 (3) | S1—C5—C51—C52 | 63.4 (3) |
N3—C35'—C5'—C4' | 80.5 (3) | C5—C51—C52—O53 | −71.4 (3) |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) −x+1, −y+2, −z. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···F3 | 0.94 (3) | 2.51 (3) | 3.321 (4) | 145 (2) |
C2—H2···F4 | 0.94 (3) | 2.33 (3) | 3.204 (3) | 156 (2) |
O53—H53···N1′i | 0.84 (2) | 1.94 (2) | 2.779 (3) | 172 (5) |
N3′—H3′···OWii | 0.88 (3) | 1.88 (3) | 2.752 (3) | 176 (3) |
OW—HW1···O53 | 1.04 | 1.69 | 2.726 (3) | 173.8 |
OW—HW2···O4′1iii | 0.87 | 1.97 | 2.808 (3) | 163.3 |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) −x+1, −y+2, −z; (iii) x, y−1, z. |
Experimental details
Crystal data |
Chemical formula | C12H16N3O2S+·PF6−·H2O |
Mr | 429.32 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 9.2881 (12), 11.9318 (13), 8.8201 (7) |
α, β, γ (°) | 91.607 (8), 92.081 (9), 112.925 (9) |
V (Å3) | 898.73 (17) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.35 |
Crystal size (mm) | 0.40 × 0.35 × 0.15 |
|
Data collection |
Diffractometer | Rigaku AFC-7R diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4485, 4133, 3430 |
Rint | 0.005 |
(sin θ/λ)max (Å−1) | 0.650 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.051, 0.154, 1.07 |
No. of reflections | 4133 |
No. of parameters | 299 |
No. of restraints | 2 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.59, −0.37 |
Selected geometric parameters (Å, º) topS1—C2 | 1.670 (2) | C35'—C5' | 1.497 (3) |
S1—C5 | 1.725 (2) | N1'—C2' | 1.310 (3) |
C2—N3 | 1.316 (3) | N1'—C6' | 1.366 (3) |
N3—C4 | 1.397 (3) | C2'—N3' | 1.347 (3) |
N3—C35' | 1.482 (3) | C2'—C2'1 | 1.490 (3) |
C4—C5 | 1.345 (4) | N3'—C4' | 1.384 (3) |
C4—C41 | 1.493 (4) | C4'—O4'1 | 1.228 (3) |
C5—C51 | 1.500 (3) | C4'—C5' | 1.439 (3) |
C51—C52 | 1.520 (4) | C5'—C6' | 1.352 (3) |
C52—O53 | 1.423 (4) | | |
| | | |
S1···O53 | 3.034 (2) | C2···F3i | 3.202 (3) |
N1'···F3 | 3.481 (3) | N3···F3i | 3.140 (3) |
C6'···F3 | 3.396 (4) | C4···F3i | 3.417 (3) |
C2'···F4 | 3.360 (3) | C4···F2i | 3.388 (3) |
N3'···F4 | 3.183 (3) | S1···F4ii | 3.664 (2) |
C4'···F4 | 3.272 (3) | C5···F4ii | 3.431 (3) |
| | | |
C2—S1—C5 | 91.04 (12) | N3—C35'—C5' | 113.17 (19) |
N3—C2—S1 | 112.72 (17) | C2'—N1'—C6' | 116.3 (2) |
C2—N3—C4 | 113.7 (2) | N1'—C2'—N3' | 122.6 (2) |
C2—N3—C35' | 124.18 (19) | N1'—C2'—C2'1 | 120.3 (2) |
C4—N3—C35' | 121.89 (19) | N3'—C2'—C2'1 | 117.1 (2) |
C5—C4—N3 | 111.6 (2) | C2'—N3'—C4' | 123.9 (2) |
C5—C4—C41 | 128.2 (2) | O4'1—C4'—N3' | 121.4 (2) |
N3—C4—C41 | 120.2 (2) | O4'1—C4'—C5' | 125.1 (2) |
C4—C5—C51 | 127.9 (2) | N3'—C4'—C5' | 113.51 (19) |
C4—C5—S1 | 110.86 (16) | C6'—C5'—C4' | 118.7 (2) |
C51—C5—S1 | 121.1 (2) | C6'—C5'—C35' | 123.1 (2) |
C5—C51—C52 | 111.3 (2) | C4'—C5'—C35' | 118.1 (2) |
O53—C52—C51 | 109.4 (2) | C5'—C6'—N1' | 124.9 (2) |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) −x+1, −y+2, −z. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···F3 | 0.94 (3) | 2.51 (3) | 3.321 (4) | 145 (2) |
C2—H2···F4 | 0.94 (3) | 2.33 (3) | 3.204 (3) | 156 (2) |
O53—H53···N1'i | 0.840 (19) | 1.94 (2) | 2.779 (3) | 172 (5) |
N3'—H3'···OWii | 0.88 (3) | 1.88 (3) | 2.752 (3) | 176 (3) |
OW—HW1···O53 | 1.04 | 1.69 | 2.726 (3) | 173.8 |
OW—HW2···O4'1iii | 0.87 | 1.97 | 2.808 (3) | 163.3 |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) −x+1, −y+2, −z; (iii) x, y−1, z. |
Oxythiamine is a potent antagonist of thiamine (vitamin B1), i.e. it competes with thiamine in the catalytic reactions of the metabolic enzymes which require thiamine pyrophosphate as a coenzyme. Oxythiamine pyrophosphate can react with the substrate in place of thiamine pyrophosphate to form a C2-substituted reaction intermediate, but the reaction does not proceed to the release of the final product, thus inhibiting thiamine catalysis (Schellenberger, 1967).
Oxythiamine differs from thiamine only in that an O atom replaces the 4'-amino group. The changes arising from this replacement should be responsible for the inhibitory effects. It has been demonstrated (Shin et al., 1979, 1981) that there are two primary differences between thiamine and oxythiamine structures. Firstly, the replacement of the 4'-amino group with an oxo group causes a change in the relative basicity of the ring N atoms. The basicity of N1' is greater than that of N3' in the aminopyrimidine ring, but N3' is more basic than N1' in the oxopyrimidine ring. Secondly, there is a change in the preferred conformation of the pyrimidine and thiazolium rings with respect to the C35' methylene bridge. The F conformation is preferred by C2-free thiamine and the V conformation by C2-free oxythiamine, where the conformations are defined in terms of the torsion angles: ϕT (C5'-C35'-N3—C2) 0° and ϕP (N3—C35'-C5'-C4') ±90° for the F form, and ϕT ±90° and ϕP ∓90° for the V-form (Pletcher et al., 1977). However, we recently reported the first X-ray evidence that C2-free oxythiamine in the structures of its hexachloroplatinate and decavanadate salts adopts the F form rather than the V form and suggested that anions play an important role in stabilizing the molecular conformation (Hu et al., 1999). The purpose of the present study of oxythiamine hexafluorophosphate monohydrate, (I), is to examine further the conformational properties of oxythiamine and the interactions of oxythiamine with anions and to compare them with those of thiamine. \sch
The molecular dimensions of oxythiamine in (I) (Table 1) agree well with those in oxythiamine chloride dihydrate (Shin et al., 1981). The structure analysis shows that oxythiamine exists as a monovalent cation with a neutral pyrimidine ring. The H atom is bonded to N3' instead of N1'. The differences between the neutral oxopyrimidine ring and the protonated form are mainly manifested by the N1'-C2' and C2'-N3' bonds and the C2'-N1'-C6' angle. The N1'-C2' bond [1.310 (3) Å] is shorter than C2'-N3' bond [1.347 (3) Å] in the neutral ring, whereas they are approximately equal in the protonated ring (Shin et al., 1979). The C2'-N1'-C6' angle becomes larger when the ring is protonated at N1'. The C5 hydroxyethyl side chain is folded back towards the thiazolium ring to make a close contact between O53 and electropositive S1 (Jordan, 1974), with O53···S1 3.034 (2) Å and the torsion angles ϕ5α (S1—C5—C51—C52) 63.4 (3)° and ϕ5β (C5—C51—C52—O53) −71.4 (3)°.
The interesting result of this work is that the oxythiamine molecule adopts the F conformation with ϕT 9.7 (3)° and ϕP 80.5 (3)°, the same as that reported for most of the thiamine structures reported (Louloudi & Hadjiliadis, 1994). This conformation is characterized by the C2—H2 bond pointing over the pyrimidine ring, with a distance of 2.49 (3) Å between H2 and the pyrimidine ring plane. This is an additional example of the conformational variability of oxythiamine. In addition to the V form, oxythiamine also assumes other conformations: the F form in (I) and in the hexachloroplatinate and decavanadate salts, and a novel V' form in the picrolonate salt (Hu et al., 1999).
What are the main factors influencing these conformations? In the crystal structure of a thiamine-dependent enzyme pyruvate decarboxylase (Dyda et al., 1993), the V conformation of thiamine pyrophosphate is stabilized by strong van der Waals interactions with the side chain of an isoleucine residue which is wedged between the thiazolium and pyrimidine rings. Aoki et al. have observed that two types of anion bridges between the thiazolium and pyrimidine rings of a thiamine molecule are of frequent occurrence in thiamine compounds with the F-form (Aoki et al., 1991, 1993). We define a type I anion bridge to be of the form C2—H···anion···pyrimidine ring and a type II anion bridge to be of the form N4'1-H···anion···thiazolium ring. Both type I and type II anion bridges exist in thiamine·PF6·H2O, which adopts the F conformation (Aoki et al., 1988). In the structure of (I), although the type II anion bridge is absent because of the change in the hydrogen-bonding scheme caused by substitution of the 4'-amino by the oxo group, the type I anion bridge is again found (Fig. 1); the C2 atom forms a bifurcated hydrogen bond with F3 and F4 of the anion (Table 3) which makes close contacts with the pyrimidine ring with the closest distance, F4···N3' 3.183 (3) Å (Table 2). Type I anion bridges have also been observed in the hexachloroplatinate and decavanadate salts of oxythiamine. These results further support the conclusion from the study of thiamine structures (Aoki et al., 1991) that the type I anion bridge is an important determinant of the F conformation. Widespread occurrence of the type I anion bridge in either thiamine or oxythiamine compounds suggests it is likely that an anionic or electronegative group from an amino acid residue in thiamine-binding proteins (Iwashima & Nishimura, 1979) is located in the vicinity of the C2 site and stabilized by this type of interaction when thiamine is in the F form.
It is of interest to note that, to a certain extent, the molecular conformation is correlated with packing modes. For example, the molecular association in a hydrogen-bonded cyclic dimer is one of the structural features of thiamine compounds with the F form, sometimes resulting in supramolecular structures (Aoki et al., 1993). The hexachloroplatinate salt of oxythiamine in the F form also shows such a cyclic dimeric structure. In the structure of (I), as shown in Fig. 2, a `head-to-tail' (`head' is the pyrimidine ring and `tail' is the hydroxyethyl side chain) cyclic dimer that involves two PF6− ions at the positions of the type I anion bridge is formed through a pair of O53—H···N1' hydrogen bonds. The dimers are linked in the b direction by hydrogen bonds involving the water molecules and are arranged in the c direction to form a molecular column with the PF6− ions sandwiched between the thiazolium rings. Table 2 lists the close contacts of a PF6− anion with these two thiazolium rings.