Proximity rules

The discovery, preparation, and industrial manufacture of QCI and QCD, and the emerging chemistry of these building blocks. Bridgehead chirality ( N-chirality ) and the proximity rule maximize stereodifferentiation of alternative diastereomeric transition states. 

The major conformational changes in disulfide bonded proteins, such as BPTl and ribonuclease A [88], can be understood in terms of disulfide bond rearrangement. Thus, the conformations of the intermediates that determine the folding pathways are specified in terms of the S-S bonds. In such proteins the S-S bonds serve as a surrogate reaction coordinate. These observations enable us to develop the proximity rule based on the following general principles. 

Proximity rule also predicts that the ratio of the maximum concentration of [30-51] to that of [5-55] is about 7 1, whereas the concentration of [14—38] is negligible on the same time scale. This ratio is in excellent agreement with the experiments of WK, who found a ratio of 6 1, and is in disagreement with Creighton s estimate of 20 1. 

C. Camacho and D. Thirumalai, Theoretical predictions of folding pathways using the proximity rule with applications to BPTI. Pmc. Natl. Acad. Sci. USA 92, 1277-1281 (1995). 

It is generally beheved that selectivity of hydrolytic enzymes strongly depends on the proximity of the chiral center to the reacting carbonyl group, and only a few examples of successful resolutions exist for compounds that have the chiral center removed by more than three bonds. A noticeable exception to this rule is the enantioselective hydrolysis by Pseudomonasfluorescens Hpase (PEL) of racemic dithioacetal (5) that has a prochiral center four bonds away from the reactive carboxylate (24). The monoester (6) is obtained in 89% yield and 98% ee. 

Note. The draft natural product rules [26] recommend that the new carbon atom takes the locant of the lower-numbered proximal atom. However, carbohydrate chemists regard the ring oxygen as formally originating from the non-anomeric (usually higher-numbered) position. 

Regression analyses revealed systematic differences between experimental log P and log P calculations based on the summation of fragment values. These differences could be attributed to chemical characteristics of the molecules, which in turn allowed the definition of correction rules such as chain conjugation, electronegativity facing bulk or the proximity effect, which describes the presence of electronegative centers in a molecule separated by one or two carbons. Correction values needed for log P calculation were shown to represent multiples of a constant value of 0.289, which is known as the magic constant (CM). 

Duplex ultrasonography is the most commonly used test to diagnosis DVT. It is a non-invasive test that can measure the rate and direction of blood flow and visualize clot formation in proximal veins of the legs. It cannot reliably detect small blood clots in distal veins. Coupled with a careful clinical assessment, it can rule in or out (include or exclude) the diagnosis in the majority of cases. 

Correct timing of antibiotic administration is imperative to preventing SSI. The National Surgical Infection Prevention Project recommends infusing antimicrobials for surgical prophylaxis within 60 minutes of the first incision. Exceptions to this rule are fluoroquinolones and vancomycin, which can be infused 120 minutes prior to avoid infusion-related reactions.1 No consensus has been reached on whether the infusion should be complete prior to the first incision. However, if a proximal tourniquet is used, antibiotic administration should be complete prior to inflation. 

This rule can be easily extended so that the classification of the majority of k nearest neighbors is used to assign the pattern class. This extension is called the k-nearest neighbor rule and represents the generalization of the 1-NN rule. Implementation of the k-NN rule is unwieldy at best because it requires calculation of the proximity indices between the input pattern x and all patterns z , of known classification. 

The spatial organization of the cell bodies of the motor neurons follows a proximal-distal rule. Motor neurons that innervate the most proximal muscles (axial muscles of the neck and trunk) lie most medially in the gray matter. Motor neurons innervating the most distal muscles (wrists, ankles, digits) lie most laterally in the gray matter. 

Many derivatives of quinones, cinnamic acids, and mucconic acids photodimerize in solid phases to give results 16> that in many cases are not in agreement with the general PMO rule of head-to-head reaction. However, it is clear that those reactions are controlled by topochemical effects, i.e. the geometry and proximity of the reactants in the solid phase. 135> Consequently, PMO theory will not be useful for calculating reactions of that type. 

---