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Figure: CAP complexed with cAMP. The geometries obtained (cyan= PCM; green = GA; yellow = combination of both) of the ligand are in very good agreement with the X-ray data (red), especially for the ribose-monophosphate subunits. Even the largest deviations are within experimental refinement accuracy (2.5 A).

Figure 12 CAP complexed with cAMP. The geometries obtained (cyan= PCM; green = GA; yellow = combination of both) of the ligand are in very good agreement with the X-ray data (red), especially for the ribose-monophosphate subunits. Even the largest deviations are within experimental refinement accuracy (2.5 A).

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Figure 1: Reaction profile for the proton shift in the GC radical cation base-pair at UBecke3LYP/D 95* //UHF/6-31G* (energies in kcal-mol-!) Figure 1: Reaction profile for the proton shift in the GC radical cation base-pair at UBecke3LYP/D 95*//UHF/6-31G* (energies in kcal-mol-!) The proton shift in the guanine-cytosine radical cation from 1 of guanine to N3 of cytosine is with 1.2 kcal/mol only slightly endothermic and has an activation barrier of 3.8 kcal/ mol, although unrestricted CI calculations at 6-31G* level have shown that more than 90% of the positive charge is lo- cated on guanine. These results show that guanine is espe- cially exposed to subsequent ionic reactions leading to muta- tions of DNA.
Figure 1: Reaction profile for the proton shift in the GC radical cation base-pair at UBecke3LYP/D 95* //UHF/6-31G* (energies in kcal-mol-!) Figure 1: Reaction profile for the proton shift in the GC radical cation base-pair at UBecke3LYP/D 95*//UHF/6-31G* (energies in kcal-mol-!) The proton shift in the guanine-cytosine radical cation from 1 of guanine to N3 of cytosine is with 1.2 kcal/mol only slightly endothermic and has an activation barrier of 3.8 kcal/ mol, although unrestricted CI calculations at 6-31G* level have shown that more than 90% of the positive charge is lo- cated on guanine. These results show that guanine is espe- cially exposed to subsequent ionic reactions leading to muta- tions of DNA.
Scheme 1: Atrop-selective ring opening of lactone- bridged biaryls 1;(°): stereochemically unstable; (*):stereochemically stable
Scheme 1: Atrop-selective ring opening of lactone- bridged biaryls 1;(°): stereochemically unstable; (*):stereochemically stable
Lactone-bridged biaryls like 1a (Scheme 1) play an im- portant role in a novel concept for the stereoselective synthe- sis of axially chiral biaryl compounds: Triggered by a nucleophilic attack to the carbonyl function, these configuratively unstable lactones can be opened so that only one of the two axially chiral, since configuratively stable atropisomeric products 2, e.g. (M)-2, results.[1]
Lactone-bridged biaryls like 1a (Scheme 1) play an im- portant role in a novel concept for the stereoselective synthe- sis of axially chiral biaryl compounds: Triggered by a nucleophilic attack to the carbonyl function, these configuratively unstable lactones can be opened so that only one of the two axially chiral, since configuratively stable atropisomeric products 2, e.g. (M)-2, results.[1]
Fig. 1b: Parallel cyclic b-sheet (8 Ala), AM1 minimum [3]. Fig. 1c: Antiparallel cyclic B sheet (8Ala), AM1 minimum [3] parallel B-sheet: CH,(Ala), COCH, AM1 minimum
Fig. 1b: Parallel cyclic b-sheet (8 Ala), AM1 minimum [3]. Fig. 1c: Antiparallel cyclic B sheet (8Ala), AM1 minimum [3] parallel B-sheet: CH,(Ala), COCH, AM1 minimum
All four compounds are potent 5-HT ,, -receptor agonists. However, their activity on the D2-receptor differs largely. The structural differences in the model-built receptors were used to rationalize the differences in activities. Volume difference maps were used to identify the major differences in spatial requirements. In the D2-receptor model the cavity which accomodates the aryl-piperazine ring system is considerably smaller than in the 5-HT ,, -receptor. This is due to a number of larger inward pointing side chains in the D2-receptor rela- tive to the 5-HT 1A -receptor on helices I (Thr in D2/Gly in 5- HT ,, ), Il (Met/Leu), III (Met/Cys) and VII (Gly/Tyr, Ala/ Ser, tle/Phe, Thr/Asn). Therefore, this site is structurally much more demanding in the D2 receptor. Especially, there is no space for a terminal extension at the phenol ring in the D2- receptor, because the site is filled by Thr on helix I (Gly in 5- HT ,, ), Met and Val on helix II (Leu and Ala in 5-HT ,, ). 1A
All four compounds are potent 5-HT ,, -receptor agonists. However, their activity on the D2-receptor differs largely. The structural differences in the model-built receptors were used to rationalize the differences in activities. Volume difference maps were used to identify the major differences in spatial requirements. In the D2-receptor model the cavity which accomodates the aryl-piperazine ring system is considerably smaller than in the 5-HT ,, -receptor. This is due to a number of larger inward pointing side chains in the D2-receptor rela- tive to the 5-HT 1A -receptor on helices I (Thr in D2/Gly in 5- HT ,, ), Il (Met/Leu), III (Met/Cys) and VII (Gly/Tyr, Ala/ Ser, tle/Phe, Thr/Asn). Therefore, this site is structurally much more demanding in the D2 receptor. Especially, there is no space for a terminal extension at the phenol ring in the D2- receptor, because the site is filled by Thr on helix I (Gly in 5- HT ,, ), Met and Val on helix II (Leu and Ala in 5-HT ,, ). 1A
In the alternative mechanism based on quantum-mechani- cal calculations a stable copper- superoxide intermediate, that is able to oxidize a second superoxide molecule, is proposed.
In the alternative mechanism based on quantum-mechani- cal calculations a stable copper- superoxide intermediate, that is able to oxidize a second superoxide molecule, is proposed.
The results clearly indicate a preference of the sp/sp-con- figuration at C3 and C5, which are in comparison with the ap/ ap-configuration 25.2 kJ-mol-! (C4 =sp) and 7.8 kJ-mol"! (C4 = ap) energetically favoured. The sp/ap-orientations take a medium energy level. The configuration at C4 has different effects on the potential energy of the molecules. While the sp/ sp/sp-configuration - as the global minimum - has a 7.3 kJ-mol! lower energy than the sp/sp/ap-structure, the ap/ap- configuration shows inverse effects. Here the C4 ap-confor- mation is 10.1 kJ-mol-! energetically more favoured than the C4 sp-configuration. The results are in good agreement with the statistic distribution of the X-ray structures. The ap/ap/ sp- as well as the ap/ap/ap-conformation - as the most unfa- vourable structures -have not been observed. The calculated global minimum of the sp/sp/sp-conformation is the most com- mon configuration in the solid state (crystal). The relevance of the different configurations with regard to the binding at the receptor site will be discussed by comparison of the MEP’s of all conformations. Table1. Energy differences AE [kJ-mol-'] of the calculated nifedipine conformations [6-31G* basis set] This results in 23 theoretical structures. Since two stereomeric pairs are identical, there remain six different con- formations. After generation of the six conformations, each of the structures was geometry optimized in a stepwise man- ner firstly using molecular mechanics (CV FF/Discover [2] ) then the semiempirical AM1 [3] method. The minimized con- formations served as input for an ab initio calculation [4] us- ing the 3-21G* basis set with complete geometry optimiza- tion. In order to deduce the potential energy and the molecular electrostatic potential (MEP) of the resulting structures, the wavefunction was calculated using the 6-31G* basis set.
The results clearly indicate a preference of the sp/sp-con- figuration at C3 and C5, which are in comparison with the ap/ ap-configuration 25.2 kJ-mol-! (C4 =sp) and 7.8 kJ-mol"! (C4 = ap) energetically favoured. The sp/ap-orientations take a medium energy level. The configuration at C4 has different effects on the potential energy of the molecules. While the sp/ sp/sp-configuration - as the global minimum - has a 7.3 kJ-mol! lower energy than the sp/sp/ap-structure, the ap/ap- configuration shows inverse effects. Here the C4 ap-confor- mation is 10.1 kJ-mol-! energetically more favoured than the C4 sp-configuration. The results are in good agreement with the statistic distribution of the X-ray structures. The ap/ap/ sp- as well as the ap/ap/ap-conformation - as the most unfa- vourable structures -have not been observed. The calculated global minimum of the sp/sp/sp-conformation is the most com- mon configuration in the solid state (crystal). The relevance of the different configurations with regard to the binding at the receptor site will be discussed by comparison of the MEP’s of all conformations. Table1. Energy differences AE [kJ-mol-'] of the calculated nifedipine conformations [6-31G* basis set] This results in 23 theoretical structures. Since two stereomeric pairs are identical, there remain six different con- formations. After generation of the six conformations, each of the structures was geometry optimized in a stepwise man- ner firstly using molecular mechanics (CV FF/Discover [2] ) then the semiempirical AM1 [3] method. The minimized con- formations served as input for an ab initio calculation [4] us- ing the 3-21G* basis set with complete geometry optimiza- tion. In order to deduce the potential energy and the molecular electrostatic potential (MEP) of the resulting structures, the wavefunction was calculated using the 6-31G* basis set.
The semiempirical calculations were performed with the MOPAC 6.0 program package, using the MNDO/PM3 hamiltonian and the AM1 hamiltonian. The ab initio calcu- lations were carried out with the HONDO 8.4 program pack- age, using the 3-21G, 4-31G, 6-31G, and 6-31G* basis sets at the Hartree-Fock level. All the structures were comp Additonally, MP2/6-31G*//6-31 tions were performed. The com stable. The imino-group is positio However, the semiempirical me the enol-tautomer for compound etely geometry optimized. G* pertuberation calcula- puted energy values show that the keto-tautomer (b) of compounds 1 and 2 is the most ned in the pyrimidine ring. thods (AM1, PM3) prefer 2a. The differences in en- ergy values of the tautomers for compound 1 and 2 depend the tautomers for compound 3 is methods and basis set used. All , MR-spectroscopic data. strongly on the used basis set. The graduation of energy of nearly independent of the calculations show that the enol-form’ (a) with a amino-group is the most stable tautomer for compound 3. The results are in agreement with
The semiempirical calculations were performed with the MOPAC 6.0 program package, using the MNDO/PM3 hamiltonian and the AM1 hamiltonian. The ab initio calcu- lations were carried out with the HONDO 8.4 program pack- age, using the 3-21G, 4-31G, 6-31G, and 6-31G* basis sets at the Hartree-Fock level. All the structures were comp Additonally, MP2/6-31G*//6-31 tions were performed. The com stable. The imino-group is positio However, the semiempirical me the enol-tautomer for compound etely geometry optimized. G* pertuberation calcula- puted energy values show that the keto-tautomer (b) of compounds 1 and 2 is the most ned in the pyrimidine ring. thods (AM1, PM3) prefer 2a. The differences in en- ergy values of the tautomers for compound 1 and 2 depend the tautomers for compound 3 is methods and basis set used. All , MR-spectroscopic data. strongly on the used basis set. The graduation of energy of nearly independent of the calculations show that the enol-form’ (a) with a amino-group is the most stable tautomer for compound 3. The results are in agreement with
The idea was to calculate the hypersurfaces of the ground state (D-A), the contact-radical-ion pair (CRIP) (A~D*) and the exciplex (A*-D) relative to the distance of the central aro- matic ring of dicyanoanthracene and the aromatic ring of hexa- methylbenzene in acetonitrile as solvent. In order to calculate the excited states we consider a sin- gles plus pair doubles Cl-expansion (PECI=n) within the VAMP program [2]. A numerical self-consistent reaction field (SCRF) technique for the calculation of the solvent effects has been used for ground and excited states.
The idea was to calculate the hypersurfaces of the ground state (D-A), the contact-radical-ion pair (CRIP) (A~D*) and the exciplex (A*-D) relative to the distance of the central aro- matic ring of dicyanoanthracene and the aromatic ring of hexa- methylbenzene in acetonitrile as solvent. In order to calculate the excited states we consider a sin- gles plus pair doubles Cl-expansion (PECI=n) within the VAMP program [2]. A numerical self-consistent reaction field (SCRF) technique for the calculation of the solvent effects has been used for ground and excited states.
Figure 1 shows the graphite lattice used for the simulations. The lattice constant is 2.42 A and the distance between the two layers is 3.35 A, in agreement with the experimental values.
Figure 1 shows the graphite lattice used for the simulations. The lattice constant is 2.42 A and the distance between the two layers is 3.35 A, in agreement with the experimental values.
Figure 2 shows dodecane, permethyldodecylsilane and dodecasilane on the basal plane of graphite. The silanes are lying, i.e. with the dihedral angle of the Si-backbone parallel to the graphite. The alkane is standing, i.e. the dihedral angle of the C-backbone is perpendicular to the substrate. (Si-atoms: red; C-atoms: blue; H-atoms: green) For the dodecasilane a large difference between the per pendicular and parallel orientation of the dihedral angle of the Si-backbone was calculated. The dodecane and the permethyldodecylsilane show only a small difference in the relative orientation of the backbone to the substrate.This sug- gests that the methyl-groups are responsible for the adsorp- tion of permethylpolysilanes. This is supported by the fact that the heat of adsorption and the number of methyl(ene) groups of the permethyldodecylsilane is about twice that of dodecane.
Figure 2 shows dodecane, permethyldodecylsilane and dodecasilane on the basal plane of graphite. The silanes are lying, i.e. with the dihedral angle of the Si-backbone parallel to the graphite. The alkane is standing, i.e. the dihedral angle of the C-backbone is perpendicular to the substrate. (Si-atoms: red; C-atoms: blue; H-atoms: green) For the dodecasilane a large difference between the per pendicular and parallel orientation of the dihedral angle of the Si-backbone was calculated. The dodecane and the permethyldodecylsilane show only a small difference in the relative orientation of the backbone to the substrate.This sug- gests that the methyl-groups are responsible for the adsorp- tion of permethylpolysilanes. This is supported by the fact that the heat of adsorption and the number of methyl(ene) groups of the permethyldodecylsilane is about twice that of dodecane.
The structures calculated were [CpML],-Clusters with M =Fe (or Co, Ru, Os in x-ray-investigations) and L =S, P. Some experimental and calculational work on these systems has been done in the last ten years. All these compounds are vertex dodecahedra with an ideal or distorted M,-tetrahedron, only depending on the number of electrons in the metal-metal antibonding MO’s.
The structures calculated were [CpML],-Clusters with M =Fe (or Co, Ru, Os in x-ray-investigations) and L =S, P. Some experimental and calculational work on these systems has been done in the last ten years. All these compounds are vertex dodecahedra with an ideal or distorted M,-tetrahedron, only depending on the number of electrons in the metal-metal antibonding MO’s.
The Journal of Molecular Modeling - the advanced way of publishing- Today the Journal of Molecular Modeling gives scien- tists the possibility to publish sophisticated presentation ma- terial without extra costs. Full colour graphics are incorpo- rated directly in the text and are not grouped together on extra pages. Videos can be delivered together with the text and no limits are set to supplementary material, everything can be incorporated, e.g. source code, program executables etc.
The Journal of Molecular Modeling - the advanced way of publishing- Today the Journal of Molecular Modeling gives scien- tists the possibility to publish sophisticated presentation ma- terial without extra costs. Full colour graphics are incorpo- rated directly in the text and are not grouped together on extra pages. Videos can be delivered together with the text and no limits are set to supplementary material, everything can be incorporated, e.g. source code, program executables etc.
The X-ray structure of 1 shows a partial cone conforma- tion with both hydroxy] groups in syn-position and one pos- sible H-bond between one hydroxyl group and the oxygen of the furan-ring. In contrast to classical calix[4]arenes the inversion of the ring leads to a diastereorisomeric partial cone conformation, where the phenol ring is anti to the dihydroxybezofurane ring, which is stabilized by a H-bond between the hydroxyl group and the carbonyl function. The mild oxidation of p-tert-butylcalix[4]arene leads to the chiral monospirodienenone 1(R = tert-butyl) as an inter- mediate for the synthesis of proximal disubstituted and didehydroxylated calixarenes [1].
The X-ray structure of 1 shows a partial cone conforma- tion with both hydroxy] groups in syn-position and one pos- sible H-bond between one hydroxyl group and the oxygen of the furan-ring. In contrast to classical calix[4]arenes the inversion of the ring leads to a diastereorisomeric partial cone conformation, where the phenol ring is anti to the dihydroxybezofurane ring, which is stabilized by a H-bond between the hydroxyl group and the carbonyl function. The mild oxidation of p-tert-butylcalix[4]arene leads to the chiral monospirodienenone 1(R = tert-butyl) as an inter- mediate for the synthesis of proximal disubstituted and didehydroxylated calixarenes [1].
7 Based on these studies we determined the pharmacophore conformation of the 3,7-diazabicyclo[3.3.1]nonan-9-ones. Thus, the protonated nitrogen atom, the keto carbonyl] func-
7 Based on these studies we determined the pharmacophore conformation of the 3,7-diazabicyclo[3.3.1]nonan-9-ones. Thus, the protonated nitrogen atom, the keto carbonyl] func-
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