Minor Structural Effects

Baird, P.B. Dervan, and D C. Rees. Structural effects of DNA sequence on T-A recognition by hydroxypyrrole/pyr-role pairs in the minor groove. J. Mol. Biol. 2000, 295, 557-567. 

For the a-Pt02 system, we find that above an electrode potential of 1.2 V, the (001) surface with bulk composition is most stable and shows only minor relaxation effects (denoted as (OOl)-O in Fig. 5.11a). This surface structure corresponds to experimental UHV measurements of surface oxides on Pt(llO), supported by DFT calculations [Li et al., 2004]. In the case of a very thin surface layer, the layer composition might even be PtO. Increasing the electrode potential above 2.0 V would cause stronger interactions with the surrounding water dipoles and lead to a o -PtO2(011) surface with an enrichment of oxygen (as 0 ) on the surface. 

Convulsive disorders are still a serious therapeutic problem and new agents are being actively sought. Classical therapy was based upon the barbiturates that are no longer in favor because of their many side effects and their suicide potential. Interestingly, a seemingly minor structural variation of phenobarbital (152, shown as its sodium salt) leads to an anticonvulsant of increased potency and which has less hypnotic activity. In this case, sodium phenobarbital serves as its own base (so the yield is limited to 50%) and reacts readily with... 

The conclusions on the mechanism of the double bond hydrogenation on metallic catalysts can be summarized as follows (1) with respect to structure effects on rate, all transition metals behave similarly (2) the reactivity of the unsaturated compounds is governed mostly by the number and size of the substituents on the carbon atoms of the double bond through their influence on adsorptivity (3) the electronic nature of the substituents plays a minor if any role. 

By inspection, atropine s effects on cognitive (NF) performance reach a maximum at about 4 hours (Fig. 60). The estimated MED50 is about 90 mcg/kg and the ID50 is about 160 mcg/kg. Onset time (Tonso) and duration (D50) at the IDso.are about 1 and 6 hours respectively. The relative central potency of atropine is the lowest of any of the belladonnoids we studied (Fig. 74). Once again, as is the case with BZ vs. EA 3167 and EA 3443 vs. EA 3580, a minor structural change makes a major difference. 

Traditional or Hj antihistamine drugs block many effects caused by histamine however, it turns out that they are not able to withstand events mediated by H2 receptors, in particular excess gastric juice secretion. In 1977 an H2-receptor antagonist, cimetidine, was proposed, which revolutionized stomach ulcer treatment. Later on, ranitidine was proposed, followed by drugs with minor structural and pharmacological differences such as famotidine and nizatidine. 

Methoprene and hydroprene are first-generation juvenoids that incorporate minor structural optimization of neotenin to increase persistence. Methoprene, 1-isopropyl (E,.E)-ll-niethoxy-3,7,11-trimethyl dodecadi-2,4-enoate (129) (bp 100 C/6.7 Pa, vp 3.5 mPa at 25°C), is soluble in water to 1.4 mg/L. The rat oral LD5Q is >34,000 mg/kg. Methoprene has been used as a mosquito larvicide, in baits for ant control, and as a catde feed-through treatment for horn fly control. Hydroprene, methyl (E,E)-3,7,ll-trimethyl-dodecadi-2,4-enoate (130) (bp 174°C at 2.5 kPa, vp 2.5 mPa at 25°C), is soluble in water to 0.54 mg/L. The rat oral LD5Q is >34,000 mg/kg. Hydroprene is especially effective against aphids and cockroaches. 

However, structural effects from the olefin on stereoselection are relatively minor, and only with trisubstituted olefins do diastereoisomer ratios exceed 95 5. 5-Halo-2-pentenes (entries 7 and 8) are exceptional in this series with both an inverted preference for formation of the cw-cyclopropane derivative and the high selectivity for this stereoisomer. Only one other... 

Complexes Containing R2(0)P Ligands. In contrast to the relatively minor trans effect and trans influence of the wide range of neutral P-donor ligands discussed above, negative ligands based on trans influence as established in the X-ray structure of (3-benzyladenine)Co-... 

Tamoxifen is a competitive partial agonist inhibitor of estradiol at the estrogen receptor and is extensively used in the palliative treatment of advanced breast cancer in postmenopausal women. It is a nonsteroidal agent (see structure below) that is given orally. Peak plasma levels are reached in a few hours. Tamoxifen has an initial half-life of 7-14 hours in the circulation and is predominantly excreted by the liver. It is used in doses of 10-20 mg twice daily. Hot flushes and nausea and vomiting occur in 25% of patients, and many other minor adverse effects are observed. Studies of patients treated with tamoxifen as adjuvant therapy for early breast cancer have shown a 35% decrease in contralateral breast cancer. However, adjuvant therapy extended beyond 5 years in patients with breast cancer has shown no further improvement in outcome. Toremifene is a structurally similar compound with very similar properties, indications, and toxicities. 

Is it known that the rate of hydrogenolysis reactions are extremely sensitive to effects of alloying, surface contamination, poisoning, etc. Consequently, in all cases where supported metals are used there must be concern as to whether apparent particle size effects are due to structure sensitivity or to some minor contamination effect. In the few cases where clean single crystal surfaces have been used there is evidence of a structure effect.338 However, the maximum change in activity between different crystal faces seems to be about a factor of 10. For Ni single crystals the (100) surface is more active than the (111) surface. A similar conclusion has been reached for oriented Ni powder samples.339... 

The discussed nonlinear phenomena during H2O2 reduction on Pt in acidic media constitute impressive examples of how small differences in the interfacial kinetics owing to structural effects, for example, or to minor changes in the composition of the electrolyte, can affect the dynamic response in a qualitative manner. 

There is now abundant structural, spectroscopic, and biosynthetic evidence to suggest that, except for the possibility of minor structural irregularities, the fundamental structures of bacterial polysaccharides consist of fairly small, regular repeating-sequences of from 1 to 7 saccharide units. Thus, as the polysaccharides are multivalent antigens, the effect of minor irregularities in their structures would, in general,... 

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