Isomers complexes

The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy, in which case additional safety and efficacy data are required. The same qualitative and quantitative composition only applies to the active ingredients. Differences in excipients will be accepted unless there is concern that they may substantially alter the safety or efficacy. The same pharmaceutical form must take into account both the form in which it is presented and the form in which it is administered. Various immediate-release oral forms, which would include tablets, capsules, oral solutions and suspensions, shall be considered the same pharmaceutical form for this purpose. 

A comparison of the activation parameters Af/ ( j) for the ammonia and ethylenedi amine (meso isomer) complexes shows that Af/ (NH3) > Af/l(en) for both chromium(III) and rhodium(III), and that Af/ (Ir) > AHt(Rh) > AHt(Cr) for both NH3 and en. These trends are in keeping with the data for substitution reactions of the corresponding mononuclear complexes (364). 

The difference in the preferred binding mode observed for the Pd- and Ni-based catalysts can be the crucial factor determining activity/inactivity of these two systems in polar copolymerization. However, the question arises about the stability of the alternative binding modes at finite temperature. If the minima were separated by relatively low barriers and fast interconversion between the two isomer complexes could occur, then this difference would be of minor importance. In order to check the stability of the two modes and get the insight into the mechanism of possible interconversions, a series of molecular dynamics simulations was performed. 

Yields Typical mass balance for the Parex-Isomer complex ... 

Complex 23a (L = PMes) reacts with KOC(=CH2)Me to afford a 70 30 mixture of 24a and 25a which, npon thermolysis, leads to methane and a mixture of 26 and the prodnct of phosphine dissociation 27 . 23a and KOC(=CH2)CH2Bu-t also provide an eqnUibrinm mixtnre of enolato and 2-oxoalkyl complexes 24b and 25b, which has also been observed between complexes frawi-[Rh OC(=CHR")R (CO)(PR3)2] (R = R = Ph, R" = H and R = R" = Me, R = f-Bn) and their 2-oxoalkyl isomers. Complex 28, containing a dianionic enolato hgand, reacts with AcCH2Bn-f at 110°C to afford the S-diketonato complex 29 , which can also be obtained by reacting 23b with two eqnivalents of KOC(=CH2)CH2Bn-f3. ... 

Complexes 3 and 4 can be considered conformers with an energy difference of 7.7 kcal/mol in favor of complex 3. The isomer complex 5 with an T)3 coordinating mode is energetically disfavored as well with an energy of 6.4 kcal/mol higher than complex 3. Thus, these open-shell systems prefer a 17 valence electron configuration at the Fe center. The formal 18 VE structures 3a and 4a and especially the q3 19 VE structure 4c do not describe these complexes well. 

While the frans-TMCHD isomer complexes preferentially with LiBr in a competitive experiment such as the one just described, a 1 1 complex of LiBr with cis-TMCHD (Compound 12 in Table I) can be prepared by a stoichiometric reaction between the free ligand and LiBr. Comparison of the solid state dissociation temperature of ds-TMCHD LiBr with that of trans-TMCHD LiBr suggests that the latter is thermodynamically more stable. Whether the kinetics of complexation favor the formation of frans-TMCHD LiBr from a mixture containing both cis- and trans-TMCHD and insufficient lithium bromide is not certain. 

The hydroxyl group of both isomers forms hydrogen bonds equally with secondary hydroxyl groups of a-CyD. Another example of a crystalline complex with a racemic compound is the j8-CyD complex with flurbiprofen. In the crystal, two j8-CyD molecules form a head-to-head dimer and a pair of (R)- and (S)-flurbiprofen is packed in the barrel-like cavity (Fig. 7.25A) [163]. In contrast, an excess of (S)-isomer was detected in the j8-CyD complex with racemic fenoprofen [157]. j8-CyD molecules form a same dimer structure in the crystal of the complex with each isomer, but the arrangement of guest molecules in the dimer cavity differs between the two crystals. Two (H)-isomer molecules are included in the head-to-head mode (Fig. 7.25B) while the head-to-tail arrangement is observed in the (S)-isomer complex (Fig. 7.25C) [158]. In fS-CyD complexes with N-acetylphenylalanine, the L-isomer is disordered in the dimer cavity while two molecules of D-isomer are included in a head-to-head mode [177]. 

Finally, some work on macrocyclic thioethers was able to show that while a metal-free tetraester of a functionalised [14]aneS4 diol was non-mesomorphic as either its cis or trans isomer, complexation to palladium(II) stiffened the whole molecular unit and allowed differentiation between the non-mesomorphic, nonlinear cis complex ((312) y = l Cr 258 I), and the mesomorphic, linear trans complex ((312) y = 1 Cr 312 (N 272) Substituted with shorter lateral arms, the palladium salts (Pd(Bp4)2) exhibited monotropic SmC phases ((312) y = 0 Cr 222 (SmC 164) I). Difunctionalized tru 5-[16]aneS4 diol palladium ((313) MX = Pd(BF4)i, y = 0,l) also exhibited monotropic phase (SmC and N, respectively for y = 0 and 1), whereas the copper derivative ((313) y = 0, MX = Cu(PF6)) was surprisingly devoid of mesomorphism. Note that some related aza macrocyclic metal complexes as potential metallomesc ens were also studied, but it appeared that none of them were found to be mesomorphic. ... 

A series of oc- and j -axial diaquo and aquocyano positional isomer complexes of cobinamide, cobyric acid, and cobinic acids-1, -2 and -3 were separated using a C,g colimm (A = 365nm) and a 30/4/64 acetonitrile/THF/water (80 mM pyridine acetate at pH 3.6) mobile phase [1265]. Retention times varied from 5.4 to 13.6min and resolution times between isomers was always >0.5min. The diaquo-cobinamide and diaquocobinic acid-2 solutes generated tailed peaks. 

A new class of membrane materials, the molecularly imprinted membranes, probably has found the highest number of applications in the pharmaceutical field, due to the great advantage of being able to discriminate enantiomers from an optically active isomer complex mixture. These types of materials, which are based on the molecular recognition from an active site of the membrane and imprinted molecule (template), are particularly used in chromatography for the separation of the enantiomers and the controlled release of pharmaceutical optically active substance. 

Mn2(CO)jQ with 1,3,5r-hexatriene yields (166), together with its (EZ) isomer.Complexes (167) and (168) have been structurally characterized as products from the photoreaction of HgRe2(CO) 2 with PhC=CPh. ° Photolysis of CpMo(CO) 2 (u-H) (ii-PPh2)Mn(CO) with butadiene yields (169) which reversibly loses CO to give... 

Figure 7 (a) 1,3-diaminopropane and (b) 1,2-diaminopropane ligand isomer complexes. 

A strong hypsochromic shift by 70 nm of the cis-isomer complexes spectra in respect to the spectra of trans-isomers can be apparently explained by the formation in a cis-form of a coordination bond between a sulfo-group and a metal cation, located in a crown-cavity. 

At photoisomerization of (trans-2d)Mg at Co= 10 - lO M, as in the case with (trans-2c)Mg " an intramolecular cis-isomer complex with short-wave absorption spectrum is formed. The constant of complexation of cis-2d with Mg ", also estimated by the competitive reaction metht, is eight times greater for cis-2c isomer. It is probably attributed to the fact that the larger the cycle the easier it satisfies the attempts of cis-2d to form an intramolecular coordination bond between 803 group and the metal cation. 

As for complexes of 2b with Mg " no experimental conditions provided the considerable hypsochromic shift in the absorption spectrum at trans-cis-photoisomerization. Moreover (cis-2b)Mg spectrum calculated by Fisher method practically coincides with the corresponding absorption spectrum of 2a. The sulfoethyl chain is probably too short to form intramolecular complex. Thus, the shorter is the sulfoalkyl N-substituent the weaker becomes the coordination bond in cis-isomer complexes and in the case of sulfoethyl derivative it is not formed at all. 

As we have shown above an intramolecular coordination bond in the complexes of cis-2c with alkaline-earth-metal cations breaks at a considerable excess of cations Cm O.1 M and a "closed" complex turns into an "open" form with longer-wave absorption spectrum. It turned out that the similar transition occurs when concentration of cis-2c complex increases under the lack of excessive metal. At C( 10 M cis-isomer complex is mostly in the "open" form. This effect is probably attributed to the dimerization of the complexes by "head-to-tail" type, intramolecular coordination bond breaks and corresponding intramolecular bonds form [16]. 

At the dilution of cis-isomer complex solution up to Co<10 M the slow transition of an "open" form into a "closed" one occurs. 

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