David A. Buckingham

The Cobalt(iii)-Promoted Synthesis of Small Peptides

Publisher Summary This chapter describes cobalt(III)-promoted synthesis of small peptides and outlines the historical development of the Co(III) method. Many of the corresponding trien complexes are also available, usually as β 2 isomers, but [Co(NH 3 ) 4 (AAO)] 2+ species are less accessible. Electrophilic metals or metal complexes, when incorporated into either the acyl or alcohol functions of the ester, might be expected to increase the rate of addition of amine. Amino acids coordinated to (en) 2 Co(III) centers are the most useful in peptide synthesis, and general routes to the preparation of these important N,O-chelates are also described in the chapter. In addition to direct activation of the carbonyl function, the metal ion also enhances C-H acidity at the α-carbon atom through the additional binding of the amine nitrogen, and proton exchange at carbon can almost certainly result in some loss of chirality, if it is not completed racemization.

Reversed-phase high-performance ion-pair chromatography of cobalt(III) coordination complexes

Abstract These experiments show that there is some sort of interaction between two (or more) complex ions which influence their distribution ratios with the stationary phase and with the ion-pair reagent. This is in addition to the ion-pair depletion effect noted previously by others at high sample concentrations. These interactions lead to species of different counterion stoichiometry, or geometry, which have sufficient lifetime on the matrix of the stationary phase to allow their separation as discrete entities. This would require abnormally slow rates for the establishment of cation-ion pair-stationary phase equilibria,.

Separation of Cobalt (III) Bis(ethylenediamine) Amino Acid Complexes by Reversed Phase HPLC

Abstract Methods for the rapid analysis of amino acid cobalt (III) bis(ethylenediamine) complexes by reversed phase high performance liquid chromatography (HPLC) are described with mobile phases containing the pairing ions, p-toluenesulphonate and hexanesulphonate. Under these conditions, the amino acid cobalt (III) bis(ethylenediamine) complexes elute in order of the relative hydrophobicities of the parent amino acids which suggests that the amino acid side chain makes a significant contribution to the retention mechanism. At high sample loadings, these complexes shows a concentration dependent peak splitting effect divergent to that normally experienced with inadequate buffering capacity of the pairing ion reagent.

Alkaline hydrolysis of [Co(cyclen)(O2CO)]+ and direct observation of deprotonated SN1CB intermediates

A stopped-flow/rapid-scan study of the hydrolysis of the carbonate chelate [Co(cyclen)(O2CO)]+ in alkaline solution ([OH−] = 0.05 to 1.0 M, 25.0 °C, I = 1.0 M (NaClO4)) has shown that the reaction follows consecutive first order steps, the first (r12 = 66 ms at [OH−] = 1.0 M) corresponding to the OH− promoted reversible ring-opening of the chelate and the second (I12 = 4.1 s at [OH−] = 1.0 M) to irreversible loss of CO32− from the cis-[Co(cyclen)(OH)(OCO2)] product. Results from 18O tracer studies show that steps occur via Coue5f8O bond cleavage. Deprotonation of amine centres in the cyclen ligand is important in both processes, with significant concentrations of the amido complex [Co(cyclen-H)(O2CO)] being generated initially, and with cis-[Co(cyclen-H)(OH)(OCO2)]− also being directly observed subsequently. The experimentally determined rate laws are interpreted in terms of SN1CB mechanisms for the ring-opening and hydrolysis reactions, with the doubly deprotonated intermediate cis-[Co(cyclen-2H)(OH)(OCO2)]2− being an important contributor to the latter.

The stereochemistry of Co(III)-amine complexes. The use of nOe and COSY 1H NMR spectroscopy to determine structure in solution

Abstract It is shown how 1D nOe and 2D COSY 1 H NMR spectroscopy can be used to assign the stereochemistry of Co(III) amine complexes. By using d 6 -DMSO as solvent together with a small quantity of DCl all non-equivalent Nue5f8 H hydrogens can be distinguished at 300 MHz. Through-space (nOe), and through-bond (COSY), associations with other Nue5f8 H and Cue5f8 H hydrogens can then be determined. This leads to a complete assignment of structure in solution. The technique is applied to the complexes syn (N), anti (N)-[Co(cyclen) (NH 3 ) 2 ] (ClO 4 ) 3 , syn (N), anti (Cl)-[Co(cyclen) (NH 3 )Cl] (ClO 4 ) 2 , anti (N), syn (Cl)-[Co(cyclen) (NH 3 )Cl](ClO 4 ) 2 , syn (N), anti (O)-[Co(Mecyclen)-(GlyO)](ClO 4 ) 2 and Δ- cis -[Co(δ-en) 2 (NO 2 ) 2 ](NO 2 ).

Mercury(II)- and nitrosyl-induced aquation of anionopenta-aminecobalt-(III) species. Reactions of the t-[Co{N(CH2CH2NH2)3}(NH3)X]2+ ions (X = Cl– or N3–) and the importance of ion pairs

Evidence is presented which demonstrates that the Hg2+- and NO+-induced aquations of t-[Co(tren)(NH3)Cl]2+,(1), and t-[Co(tren)(NH3)(N3)]2+, (2), respectively, follow different paths; i.e. that a common intermediate of the type [Co(tren)(NH3)]3+ is not involved [tren = 2,2′,2″-triaminotriethylamine, N(CH2CH2NH2)3]. Saturation entry of NO3– to form t-[Co(tren)(NH3)(NO3)]2+(3) occurs as [NO3–] is raised to 1 mol dm–3[48% for (1); 35% for (2)] and this limiting condition is interpreted in terms of pre-formed ion pairs (Kipca. 5 dm3 mol–1). Second-order rate constants for the Hg2+-induced reaction of p-[Co(tren)(NH3)Cl]2+ and t-[Co(tren)(NH3)Cl]2+, are 5.6 ± 0.2 and 9.7 ± 0.1 dm3 mol–1s–1 respectively.

Reversed-phase high-performance liquid chromatography of pentaammine cobalt(iii) complexes

Abstract The reversed-phase high-performance liquid chromatography of a variety of [Co(NH 3 ) 5 X] 2+ cations including halo (X ue5fb F − , Cl − , Br − , I − ), isomeric anionato (X ue5fb ONO − , NO 2 − ; NCS − , SCN − ), anionato (X ue5fb NO 2 − , NO 3 − , N3 − , Cl − ), carboxylato (X ue5fb CH 3 C0 2 − , CF 3 C0 2 − , C 2 ,H 5 CO 2 − , C 3 H 7 C0 2 − ), isomeric toluato (X ue5fb CH 3 C 6 H 4 CO 2 − ), some [Co(NH 3 ) 5 X] 3+ cations (X ue5fb H 2 O, (CH 3 ) 2 SO, NH 3 ) and [Co(en) 3 ] 3+ are reported. In general good separations are achieved using 25 m M toluenesulphonate ion-pairing reagent in water-methanol (isocratic or gradient) using a μBondapak C 18 column. The efficiency and speed of the separations are superior to those obtained by ion-exchange chromatography.

[(NH3)5CoOP(H)(O)OCo(NH3)5]4+ and its conjugate acid; evidence for the P+O− description of a terminal PO bond

Abstract Bromine oxidation of the phosphite-bridged dimer [(NH 3 ) 5 CoOP(H)(O)OCo(NH 3 ) 5 ] 4+ ( 1 ) in acidified aqueous solution (25°C, I =1.125 M, NaClO 4 ) gives the corresponding phosphato complex [(NH 3 ) 5 CoOP(OH)(O)OCo(NH 3 ) 5 ] 4+ . The reaction follows the rate law k obs = kK a [dimer] T /( K a +[H + ])(1+ K Br 3 [Br − ]), with K Br 3 (=[Br 3 − ]/[Br 2 ][Br − ])=17.6 M −1 , and with K a (0.074±0.006 M) corresponding to the acidity constant of the acid conjugate [(NH 3 ) 5 CoOP(H)(OH)OCo(NH 3 ) 5 ] 5+ ( 2 ), and k (1.00±0.05 M −1 s −1 ) to the rate constant for oxidation of 1 . The reaction is interpreted as involving attack by free Br 2 on the O-atom of the terminal Pue5f8O group in 1 and rate-determining Pue5f8H bond breaking. The acidity constant of 2 was confirmed by independent spectrophotometric determination, K a =0.09±0.01 M, 25°C, I =1.0 M. Crystal structures are reported for both 1 (ClO 4 ) 4 ·2H 2 O and 2 (ClO 4 ) 5 ·C 2 H 5 OH. The available evidence suggests that the terminal Pue5f8O bond in 1 is best represented as a limiting case of the P δ+ ue5f8O δ− description.

Oxyanion chelates of cobalt(III). Oxygen exchange, chelate ring opening and closing and hydrolysis of monodentates

Abstract This Comment summarizes present understanding of the rates and mechanisms of O-exchange and chelate ring opening and closing in oxyanion chelates of Co(III); oxalate and glycinate (5 membered), (3-alaninate and malonate (6 membered), and phosphate, carbonate, and sulfate (4 membered). Under some conditions the product monodentate species isomerize between cis and trans configurations about the metal and these isomers differ in their ability to recyclize. Also complete hydrolysis from the metal may occur in competition with, or instead of, recyclization. Thus complete hydrolysis, as well as recyclization, of the monodentates needs to be considered.

unsym-fac-(exo-OH)-[Co(dien)(dapo)(N3)][ZnCl4]

Structural analysis of the title compound, [N-(2-aminoxadethyl)-1,2-ethanedixadamine]xadazido(2-hydroxy-1,3-propanexaddixadamine)xadcobalt(III) tetraxadchloroxadzincate(II), unsym-fac-(exo-OH)-[Co(dien)(dapo)N3]ZnCl4 or [Co(N3)(C4H13N3)(C3H10N2O)][ZnCl4], confirms both the facial configuration of the N-(2-aminoxadethyl)-1,2-ethanedixadamine (dien) ligand and the exo stereochemistry of the OH substituent of the 2-hydroxy-1,3-propanexaddixadamine (dapo) ligand relative to the azide ligand.