Гидрофобность

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∆Gu, ddZe•fhev-1
KG4 \ [_gahe_ → KG4 \ G2H
-2,8
-18
+2,6
KG4 \ wnbj_ → KG4 \ G2H
-2,4
-19
+3,3
KG4 \ CCl4 → KG4 \ G2H
-2,5
-18
+2,9
K2G6 \ [_gahe_ → K2G6 \ G2H
-2,2
-20
+3,8
K2G6 \ CCl4 → K2G6 \ G2H
-1,7
-18
+3,7
@b^dbc K3G8 → K3G8 \ G2H
-1,8
-23
+5,05
@b^dbc g-K4G10 → g-K4G10 \ G2H
-1,0
-23
+5,85
0
-14
+4,07
J_Zdpby i_j_ghkZ
@b^dbc K6G6 → K6G6 \ G2H
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bawlZehgZ\\h^mijbK
Kh_^bg_gb_
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-4,63
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-3,90
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<Zebg
-2,94
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Kh_^bg_gb_
G, ddZe/fhev
Gi_j,ddZe/fhev
WlZg
+3,02
-
+1,69
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+2,26
-
-2,21
+2,42
WlZg – f_lZg
-
+0,76
Bahe_cpbg
-1,69
+2,97
:eZgbg – ]ebpbg
-
+0,73
N_gbeZeZgb
g
Ijhebg
-1,98
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-
0,73
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6
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P = ----------- , [fhevV]
[X]aq
z
Mkeh\byhij_^_e_gby
- khklhygb_jZ\gh\_kby
- \aZbfghgZkus_ggu_jZkl\hjbl_eb
- h^bgZdh\ZynhjfZ\_s_kl\Z\h[hbojZkl\hjbl_eyo
7
Bhgbabjh\Zggu_
jZkl\hj_ggu_\_s_kl\Z
HA
+
BH
+
-
H + A (1)
+
B + H (2)
Ka1 = a(H + )a(A- )/a(HA)
+
+
Ka2 = a(H )a(B)/a(BH )
(pH-pKa)
P=Papp[1+10
]
(pKa-pH)
]
P=Papp[1+10
>eykeZ[uodbkehl (pKa>>7)
bkeZ[uohkgh\Zgbc (pKa<<7)
} (P=Papp).
8
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- «shake-flask» f_lh^
- f_lh^]_g_jZlhjghcdhehgdb
- HPLC-f_lh^
- f_lh^ihl_gpbhf_ljbq_kdh]h
lbljh\Zgby ^eykeZ[hbhgbabjh\Zgguo\_s_kl\
-dhwnnbpb_glZdlb\ghklb=_gjb
K = 0.115γw/γ0
-bkihevah\Zgb_njZ]f_glguo
dhgklZgl
- f_lh^dhjj_eypbbJb
\h^ghcjZkl\hjbfhklb
log P = 5.2-0.68 log S
log P = 6.5-0.89(log S)-0.015(mp)
(r = 0.94) – Hansch
(r = 0.96) - Yalkowsky
9
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10
HPLC – f_lh^
V0
P=
Vs
¯ k´=
Vr - V0
Vs
]^_
P – dhwnnbpb_gljZkij_^_e_gby
Vr – h[tzfm^_j`Zgby
V0 – h[tzfih^\b`ghcnZau
Vs – h[tzfklZpbhgZjghcnZau
k´ – nZdlhjzfdhklb
11
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12
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13
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14
:e]hjblfijh]jZffuQSAR/QSPR
Ih^]hlh\dZ\oh^guo^Zgguo
of_jgZyhilbfbaZpby
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"$!#\u\h^bij_^kdZaZgb_
15
Y^_jgh-nbabq_kdb_ oZjZdl_jbklbdb ljblby
3H
T1/25,6 dw<T1/2 =
→
12,4 e_l
3He
+ e-
Emax =
Eaver =
+ νe
18,6 dw<
5,6 dw<
Ijh[_] β-qZklbp \ \ha^mo_ 0,6 kf
\ [bheh]bq_kdhc ldZgb ∼ 1 fdf
16
Ebl_jZlmjZ
1.
2.
3.
4.
5.
6.
J. SANGSTER. Octanol-water partition coefficient of simple organic
compounds. //J. Phys. Chem. Ref. Data, Vol. 18, No.3, 1989
W. A. BRUGGERMAN, J. VAN DER STEEN, O. HUTZINGER.
Relationship with hydrophobicity as measured by aqueous solubility and
octanol-water partition coefficient. //Journal of Chromatography, 238
(1982) 335
ALAN R. KATRITZKY, VICTOR S. LOBANOV, MATI KARELSON.
QSPR: the correlation and quantitative prediction of chemical and physical
properties from structure //CHEMICAL SOCIETY REWIEWS, 1995
D. N. Brooke, A. J. Dobbs, and N. Williams. Oktanol:Water Partition
Coefficient (P): Measurement, Estimation, and Interpretation, Particularly
for Chemicals with P > 105 .// ECOTOXICOLOGY AND
ENVIROMENTAL SAFETY 11, 251-260 (1986)
Q:JEVAJD:GLHJIHEJRBFF?E;bhnbabq_kdZyobfby<oli_jkZg]e. – FFbj– L
SUJIT BANERJEE, SAMUEL H. YALKOWSKY, SHRI C. VALVANI.
Water solubility and octanol/water partition coefficient of organics.
Limitations of the solubility-partition coefficient correlation // American
Chemical Society, Vol. 14, Number 10, October 1980
17
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