高等无机化学英文课件：wang_part1-1VIP

1、分子识别 Molecular Recognition Recognition, Information, Complementarity Molecular recognition is defined by the energy and the information involved in the binding and selection of substrate(s) by a given receptor molecule; it may also involve a specific function. In another words, recognition is bindin

2、g with purpose. Binding: stability and selectivity,Molecular recognition implies the (molecular) storage and (supramolecular) read out / expression / processing of molecular information. Information: a key notion of supramolecular chemistry Supramolecular Chemistry = “Chemical information science or

3、 molecular informatics” Molecular recognition implies geometrical and interactional complementarity between the associating partners, i.e., optimal information content of a receptor with respect to a given substrate. Energetic and Geometrical,Coordination mode of 2,2-bipy: chelate ligand,MnCl(2,2-bp

4、y)2)22+2 dimer in (MnCl(bpy)2)22+(I3-)2(I2) by us,Structure of Co(4,4-bipy)1.5(NO3)2CS2 by M. J. Zaworotko et al., New J. Chem., 1998, 177,Coordination mode of 4,4-bipy: bridging ligand,Different aromatic carboxylic acids linked via hydrogen bond pattern (synthon): a) dimer, b) linear tape, c) crink

5、led tape, d) planar sheet,Factors taken into account for high recognition between receptor and substrate : 1. steric (shape and size) complementarity between and , i.e., presence of convex and concave domains in the correct location on and on , 2. interactional complementarity, i.e., presence of com

6、plementary binding sites (electrostatic such as positive/negative, charge/dipole, hydrogen bond donor/acceptor, etc.) in the correct disposition on and on so as to achieve complementary binding, 3. large contact areas between and so as to contain,4. multiple interaction sites, 5. strong overall bind

7、ing = high stability and high selectivity; and 6. medium effect: hydrophobic / hydrophobic, hydrophilic / hydrophilic, (solvophobic, solvophilic) How? Based on the knowledge of structural chemistry, molecular modeling method,Supramolecular chemistry in life Biological molecular recognition represent

8、s the most complex expression of molecular recognition leading to highly selective binding, reaction, transport, regulation etc. It provides study cases, illustration and inspiration for the unraveling of basic principles and the design of model systems as well as of abiotic receptors,糜蛋白酶、胰蛋白酶和弹性蛋白

9、酶 功能：消化蛋白质的酶，断裂肽键 J. M. Berg, J. L. Tymoczko, L. Stryer, Biochemistry, 5th Ed., W. H. Freeman and Company, New York, 2002, chap. 9, pp227-235,结构：Ser-His-Asp三联体，活性中心，或切断肽键的“牙齿,Ser-His-Asp triad,The oxyanion hole stabilizes the tetrahedral intermediate,The catalytic triad,催化机理：氢键化学键的转化（Lewis酸碱反应,专一性或选

10、择性： 各种蛋白酶有选择地切断肽键，选择性由酶上的与底物多肽链上的残基结合（分子间相互作用）的口袋的选择性决定,糜蛋白酶,糜蛋白酶 胰蛋白酶 弹性蛋白酶,Myoglobin and Hemoglobin O2 take up and transport,肌红蛋白和血红蛋白,The stability of biological Heme-O2 complexes arise from: (1)Heme in a hydrophobic pocket in the protein inaccessible by water and proton (2)Bent binding of O2 res

11、ults: Avoiding -oxo dimmer formation Favorable bonding characters for O2 takeup, transfer and selectivity (KCO/KO2 from 25000 (protein free Heme) to 200 (protein Heme,Irreversible -oxo dimmer formation in nonprotein iron porphyrin,Bent binding of O2 in protein,Weiss model for oxy form: low spin Fe3+

12、 + O2,Improved selectivity for O2 over CO is enforced by the protein environment CN,KCO/KO2 =25000,KCO/KO2 =200,K+ channels Roderick Mackinnon, et al., Science, 1998, 280, 69-77； 2003 Nobel Prize of Chemistry, 1/2 shared (other 1/2: Peter Agre, Water channels, P. Arge et al., Journal of Physiology,

13、2002, 542, 1, 3-16, FEBS letters, 2003, 555, 72-78) Angew. Chem. Int. Ed., 2004, 43, 4264-4290,Function: K+ diffusion across cell membrane electrical signaling in the nervous system, etc. Selectivity: K+ 10000 times more permeant than Na+ (K+ Rb+ Cs+) Throughput rate: 108 ions per second What is the

14、 mechanism at molecular level,D: aspatic acid G: glycine Y: tyrosine G: glycine V: valine T: threonine Green ball: K+ ions (7.5 apart from each other) Red ball: water,Narrow hydrophilic filter Wide hydrophobic cavity or channel,Top view,Roderick Mackinnon, FEBS Letters, 2003, 555, 62-65,DNA Watson-Crick base paring, G-C and A-T,DNA double helix,Anti-cancer drug,Pt(NH3)2Cl(H2O),X-ray structure of cis-Pt(NH3)22+d(pGpG,Pt,DNA intercalators through - stacking,Rh(R, R-Metrien)(phi)3+ - DNA complex,Hydrogen bonding of netropsin with the 5-AATT-3