Selectivity reversal

Ideal Adsorbed Solution Theory. Perhaps the most successful approach to the prediction of multicomponent equiUbria from single-component isotherm data is ideal adsorbed solution theory (14). In essence, the theory is based on the assumption that the adsorbed phase is thermodynamically ideal in the sense that the equiUbrium pressure for each component is simply the product of its mole fraction in the adsorbed phase and the equihbrium pressure for the pure component at the same spreadingpressure. The theoretical basis for this assumption and the details of the calculations required to predict the mixture isotherm are given in standard texts on adsorption (7) as well as in the original paper (14). Whereas the theory has been shown to work well for several systems, notably for mixtures of hydrocarbons on carbon adsorbents, there are a number of systems which do not obey this model. Azeotrope formation and selectivity reversal, which are observed quite commonly in real systems, ate not consistent with an ideal adsorbed... 

Patemo-Biichi reaction between 2-methylfuran 31 and an a-hydroxyaldehyde 30 to form the core oxetane. Two of the three stereocenters set in the electrocyclization appear in the final product while the third is selectively reversed with anomeric assistance. 

Synthetic heterocyclic and modified amino acid derivatives have been grouped in a class of thrombin inhibitors called peptidomimetics. An example of such a compound is argatroban, with a molecular mass of 532 Da. It blocks thrombin s active catalytic site by binding to the adjacent apolar binding site. This selective reversible inhibitor of thrombin has a K of 19 nM and blocks thrombin s role in coagulation and fibrinolysis (62). 

A group of peptide derivatives such as peptide arginals and boronic acid peptide derivatives belong to another class of reversible thrombin inhibitors. One such inhibitor is PPACK (D-Phe-Pro-Arg chloromethyl ketone), which functions as a powerful irreversible thrombin inhibitor by alkylating the histidine residue at the catalytic site of thrombin (58). It, however, is unstable in neutral solution, as it undergoes cyclization and inactivation. However, the D-methyl derivative of D-Phe-Pro-Arg-H (D-Mephe-Pro-Arg-H) called efegatran, with a molecular mass of 515 Da, is a stable selective reversible inhibitor of thrombin with a K. of approximately 100 nM. The basic amino terminus in this compound is responsible for promoting the specificity toward thrombin (63). 

Hurst, L.D. and McVean, G.T. (1996) Clade selection, reversible evolution and the persistence of selfish elements the evolutionary dynamics of cytoplasmic incompatibility. Proceedings of the Royal Society of London B 263, 97-104. 

Compound SR 95191 (42, CAS 94011-82-2) is another aminopyridazine-derived antidepressant agent structurally closely related to minaprine, which has been investigated in France quite recently [ 160-162], This compound has been shown to be active in most animal models of depression with an activity profile resembling that of a selective type A MAO inhibitor [ 160], Recently, it has been found that this inhibition is selective, reversible and competitive in vivo in vitro, however, SR 95191 behaves like an irreversible MAO-A inhibitor [162],... 

DISFAVOURED REGIO- AND STEREO-SELECTIVITY Reversal of kinetic control in a ring closure reaction... 

Earlier it was noted that nickel and cobalt could be extracted by carboxylic and sulfonic acids, with nickel being extracted at the lower pH. However, with alkylphosphorus acids, a selectivity reversal is observed, with cobalt being favored under acid conditions. The cobalt-nickel separation factor has been shown to depend upon metal concentration, reagent structure, diluent, temperature, and the presence of a diluent modifier. Thus, with increasing cobalt concentration the color of the extractant phase changes... 

The ratio of the isomeric trienes (36, 37, and 38) is governed by the nature of the rhodium catalyst. For example, when the catalyst was changed to a cationic rhodium(I) species ([Rh(COD)Cl]2/AgBF4), the /Z-selectivity reversed and gave exclusively the H-isomer, while the constitutional group selechvity was dramatically decreased to a 1 1 ratio (entry 3). Furthermore, lower reachon temperatures and changing the catalyst to a cahonic iridium(I) species furnished the -isomer 36 selectively (entries 4—6). Clearly, additional work is required to increase and understand the selechvity issues [33]. 

Among bicyclic compounds mercapto amide 394b is one of the most potent substances (96JME494,97JME1570). Amidolactam 362, on the other hand, is an excellent selective, reversible inhibitor of enzymes caspase-1 and caspase-3 (98BML2757). 

Pig. 1. Pulse sequence for selective reverse INEPT. The time-shared homonuclear decoupling during acquisition is optional, and a variety of simplifications may be made to the sequence depending on the instrument used and on the spin system under investigation, as discussed in the text. A DANTE sequence is shown as the selective 90° carbon-13 pulse, but this may be replaced by a soft pulse or some other form of selective excitation. Phase cycling for this sequence is summarized in table 1. 

Phase cycling scheme for the selective reverse INEPT pulse sequence of fig. 1. Phases are shown in multiples of 90° subscripts indicate that a given phase or bracketed block of phases should be repeated the stated number of times, e.g., the notation (01)2 (13)2 indicates the sequence 0101 1313. Phases in the sequence of fig. 1 other than those listed above remain unchanged in successive transients. 

Fig. 2. Pulse sequence for selective reverse INEPT using pulsed field gradients to select the coherence transfer echo. The 180° pulse pair in the middle of the 2r delay is not normally needed for t < 50 ms, and the second proton 180° pulse and first t2 delay maybe omitted if a linear phase gradient in the resultant spectrum can be tolerated. The second field gradient pulse has an area (7c/th) times that of the first.

Fig. 4. (a) 300 MHz proton spectrum and (b)-(e) selective reverse INEPT spectra of 28% menthone (Aldrich) in acetone-ds, measured using a 5 mm sample in the 10 mm broadband probe of a Varian Associates XL300 spectrometer using the sequence of fig. 1. The sample contains substantial quantities of isomenthone, seen clearly in the methyl region of trace (a). Spectra (b) to (e) used selective excitation of carbon sites 6, 7, 2 and 8, respectively, with delays 2r of 3.85, 3.85, 1.92 and 1.54 ms. 32 transients were used for each trace no spin lock pulses or 180° pulses were used. Traces (b) to (e) have a vertical scale lOOOx that of trace (a). No homodecoupling was used during acquisition. 

A. Najafi, A. Peterson, M. Buchsbaum, S. O Dell, F. Weihmuller, Preparation and preliminary biological evaluation of [F-18]NCQ-115—A new selective reversible dopamine D2 receptor ligand, Nucl. Med. Biol. 20 (1993) 549-555. 

Over the years, many reversible competitive inhibitors selective for MAO A have been developed, including many a-methylamines. In contrast, very few effective MAO B-selective reversible inhibitors have been reported to date. Accumulated experience has indicated that a-alkylamines are inhibited steiically from binding to MAO B—and thus are MAO A selective. No complementary steric inhibition selective for MAO A is available [6b]. However, it was demonstrated that, while 5-fluoro-a-methyltryptamine (5) is a selective MAO A substrate, jS-substitution, as in p-chloro-/J-methylphenylamine (6), favors MAO B selectivity [28]. 

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