Äîêóìåíò âçÿò èç êýøà ïîèñêîâîé ìàøèíû. Àäðåñ îðèãèíàëüíîãî äîêóìåíòà : http://mgumus.chem.msu.ru/ru/researches/sem021219/vita-191202.pdf Äàòà èçìåíåíèÿ: Sat Jan 4 18:01:40 2003 Äàòà èíäåêñèðîâàíèÿ: Mon Oct 1 21:39:12 2012 Êîäèðîâêà:

=b^jhnh[ghklv

ZkibjZgldZdZn_^ju jZ^bhobfbb Iha^gydh\Z

Kh^_j`Zgb_
z z

z z z

Hij_^_e_gb_ihgylby]b^jhnh[ghklb Dhwnnbpb_gljZkij_^_e_gbydZd dhebq_kl\_ggZyf_jZhij_^_e_gby ]b^jhnh[ghklb KemqZc^bkkhpbbjh\ZgguojZkl\hjzgguo \_s_kl\ F_lh^ubaf_j_gby ijZdlbq_kdh_bkihevah\Zgb_dhwnnbpb_glZ jZkij_^_e_gby
2


=b^jhnh[ghklv K\GRU\h^Z

Ibjj_g­ ]

Ebhnh[ghklv KRERV[hyagvkljZo

KRERV[hyagvkljZo

O\SRVfZkeh

=b ^j hnh[ghh_\a Zb fh^_ckl \b_
3


:>h^_dZw^jh[jZah\Zggucfhe_dmeZfb\h^ubkh^_j`Zsbc ihehklv^bZf_ljhfhdheh: ;DeZkl_j^h^_dZw^jh\
4


5


L_jfh^bgZfbq_kdb_iZjZf_ljui_j_ghkZ jZaebqguom]e_\h^hjh^h\ bag_iheyjguojZkl\hjbl_e_c\\h^mijbK
J_Zdpby i_j_ghkZ KG4 \ [_gahe_ KG4 \ G2H KG4 \ wnbj_ KG4 \ G2H KG4 \ CCl4 KG4 \ G2H K2G6 \ [_gahe_ K2G6 \ G2H K2G6 \ CCl4 K2G6 \ G2H @b^dbcK3G8 K3G8 \ G2H @b^dbcg-K4G10 g-K4G10 \G2H @b^dbcK6G6 K6G6 \ G2H G,ddZe·fhe-1 -2,8 -2,4 -2,5 -2,2 -1,7 -1,8 -1,0 0 Su, dZe·]jZ^-1·fhev-1 -18 -19 -18 -20 -18 -23 -23 -14 Gu, ddZe·fhev-1 +2,6 +3,3 +2,9 +3,8 +3,7 +5,05 +5,85 +4,07

K\h[h^gZywg_j]byi_j_ghkZjZaebqguokh_^bg_gbc bawlZehgZ\\h^mijbK
Kh_^bg_gb_ =ebpbg :eZgbg 2

G, ddZe/fhev +3,02 +2,26 -

Gi_j,ddZe/fhev +0,76 +0,73 0,73

6


Dhwnnbpb_gljZkij_^_e_gbydZd dhebq_kl\_ggZyf_jZhij_^_e_gby ]b^jhnh[ghklb
z z

H[hagZq_gby: K,KD,KP,D bP >\monZagZykbkl_fZhdlZghe-\h^Z: OWPC [X]org P = ----------- , [fhevV] [X]aq
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=P

app

).

8


F_lh^ubaf_j_gby
ijyfu_dhk\_ggu_
- «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 = 0.115w/0 -bkihevah\Zgb_njZ]f_glguo dhgklZgl - f_lh^dhjj_eypbbJb \h^ghcjZkl\hjbfhklb (r = 0.94) ­ Hansch (r = 0.96) - Yalkowsky
9

log P = 5.2-0.68 log S log P = 6.5-0.89(log S)-0.015(mp)


«Shake-flask» f_lh^
· · · · Mkeh\by QbklhlZjZkl\hjy_fh]h\_s_kl\Z
Ijbf_gy_lky^eybaf_j_gby\ukhdbo agZq_gbcJ

10


HPLC ­ f_lh^
V0 P= V s ¯ 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


Bkihevah\Zgb_baf_j_gbcjZkij_^_e_gby




Hp_gdZhiZkghklblhdkbqghklb\_s_kl\ \hdjm`Zxs_ckj_^_ bamq_gb_bij_^kdZaZgb_nbabq_kdbob [bheh]bq_kdboy\e_gbcihq\_ggh-k_^bf_glZpbhggZy Z^khj[pby[bhZddmfmeypby) \f_^bpbg_bnZjfZp_\lbd_baf_j_gb_jZkl\hjbfhklbb kdhjhklbjZkij_^_e_gbye_dZjkl\ baf_j_gb_jZ\gh\_kby baf_j_gb_kihkh[ghklb]b^jhnh[gh]hk\yau\Zgby ij_^kdZaZgb_[bheh]bq_kdhcZdlb\ghklbobfbq_kdbo kh_^bg_gbc
12



13


=BIHL?LBQ?KD:Y KLJMDLMJG:Y NHJFME: =D IHQ<
2 2+ +22& 2+ 2+ 2 2+ + 2


2+

+22&

2

2+



&22+ 1 )H


2+ 2 +22& 2+ 2+ 2 2 &+ 2+ 2+ 2



+ 2 2


1+

2



2

2+ 2 2 2 + 2


+

)H

2



1+ 2 &+ 2 &+ 1+ 2 2+ 1 2




2 2 2

2+ 6L 2 $O 2+ $O


2

+ 2

+

++ 22 )H 1+ 2

2

2

2+ 2 + 2 )H


2 + 2


1+ 1+ 2+ 1+ 2 + & 1+ 1+ 2+ &+ 2+ 1+ 2 2+ 2&+ 2 2+ 2 2+ &+ 2 2 2 2 1+ &+ 2+ 2+ 2 2 2+ 6L + 2 &22+ 2+ 2 +2 1+ 1 1+ &+ 1+ 1+ &+ & 2 &+ &+ &+ &+ 2 2 &+ +2 2+ &+ &+ 1+ 2 +1 1 12 + &2 &+ + & 2+ &22+ 2+


&22+ &22+ 1+ &+ &+ 1+ 1+ 2



2



.



2 2

2 6L 2

2 2 +

+ 2

)H 2 2+

2 +

+1 2




&+ 2

&+ + 2+ 1+




2 2+ + 2+ + &+ 2+ 1+ &+


+2 + &

1+ +2 +2

2+ 2

2 2+ 2 +2

2+

2+ 2


2+

2+ 2 1

+ + 2 &+


&+ 2+ 2 2 2 2 2 &+


&+ 2+ 2 2

2 &+ 2+ 2

2

&+ 2+ 2 2 &+ 2+

2 2+

2+ 12



2+ + 1

2

2+

2

14


:e]hjblfijh]jZffuQSAR/QSPR

Ih^]hlh\dZ\oh^guo^Zgguo
of_jgZyhilbfbaZpby 15


Y^_jgh-nbabq_kdb_ oZjZdl_jbklbdb ljblby

12,4 e_l

3

H

3He

+ e-

+

e

T1/25,6 dw
Emax = Eaver =

18,6 dw< 5,6 dw<

Ijh[_] -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 17