Methylamine, model

Andres J, Moliner V, Krecbl J, Silla E (1993) A theoretical study of the addition mechanism of carbon dioxide to methylamine. Modelling C02-biotin fixation. J Chem Soc Perkin Trans 2 521-523... 

The symmetric and antisymmetric stretching vibrations of methylamine can be viewed on Learning By Modeling... 

The structures of PMs are trimeric, consisting of three molecules of PS and two molecules of methylamine that are condensed together (Table 9.5). In the structures of PMs, however, the bonds created by the condensation lack adjacent hydrogen atoms, making the connectivity assignment in 1H-NMR studies virtually impossible (see the 9-membered rings in Fig. 9.11). To circumvent this problem, a model compound of panal, K-l, having 13C-labeles at the C12 and C13 positions, has been synthesized at Kishi s laboratory (Harvard University) to make a model compound of PM (Stojanovic, 1995). 

In the activation of PS-A and PS-B, treatment with methylamine resulted in a considerably higher chemiluminescence activity than with other amines. In the case of K-1, however, a significantly higher chemiluminescence activity was obtained with (NH SC or with hexy-lamine than with methylamine. In spite of this finding, methylamine was used in the activation of K-1 to prepare a model compound of PM. 

Fig. 9.10 Absorption spectra of K-1 (a model compound) and its chemiluminescent methylamine-activation products KM-1 and KM-2. All in methanol.

Treatment of the precursors with decylamine resulted in a high level of chemiluminescence activity. Taking the activity obtained with decylamine as 100%, the activities obtained with other amines were methylamine, 5% hexylamine, 23% octylamine, 39% and dode-cylamine, 55%. For comparison, the Panellus precursors, PS-A and PS-B, are best activated with methylamine, and a synthetic model compound, K-l, is best activated with hexylamine. 

MePO2- or PME2- (Table XIX), but the open closed equilibrium lies very much on the side of the chelated form of the complex (87% for the Ca2+ complex - compare 15% for [Ca(atp)]2 and just 7% for [Ca(amp)] (695)). The availability of stability constants both for methylphosphonate and for benzimidazole (a purine model) complexes means that the chelate effect for complexes of (1H-benzimidazol-2-yl-methyl)phosphonate can be discussed without the usual complications, such as the differences between ethane-1,2-diamine and two ammonia or two methylamine ligands and disparities between units (704). 

Using a model system of H-STXOL/PNPCF/ C-methylamine we have found that we can reliably obtain a good yield of the STXOL/amine product if STXOL solubility and solvent purity are carefully controlled. However, the same reaction conditions generally fail to produce a useful [STXOL]n-protein (n<2) preparation. 

Semi-empirical models are markedly inferior to all other models dealt with (except the SYBYL molecular mechanics model) for barrier calculations. Major trends in rotation barriers are often not reproduced, for example, the nearly uniform decrement in rotation barrier from ethane to methylamine to methanol. None of the semi-empirical models is better than the others in this regard. One the other hand, AMI is clearly superior to MNDO and PM3 in accounting for nitrogen inversion barriers. All in all, semi-empirical models are not recommended for barrier calculations. 

Data on molecules containing nitrogen, oxygen, silicon, phosphorous and sulfur not only provide additional examples, but also allow assessment of the ability of the different models to reproduce known changes in dipole moments accompanying structural variations. For example, dipole moments in methylamines are known experimentally to decrease with increasing methyl substitution,... 

The two-dimensional PES shown in Figure 8.17 (as well as in Figures 8.3b and 8.7c) is typical of internal rotation coupled to inversion of the other part of the system. This situation is also realized in methylamine inversion, where the rotation barrier is modulated not by a harmonic oscillation but by motion in a double-well potential. The PES for these coupled motions can be modeled as follows ... 

Effects of solvation on zwitterion formation between methylamine and fom-aldehydewere studied by various solvation methods. The SM2/AM1 model predicted the expected zwitterionc minimum while SM3/PM3 failed to do so [127]. Calculations were performed with the use of AMSOL to account for solvation effects in the study of molecular properties and pharmacokinetic behavior of ce-tirizine, a zwitterionic third-generation antihistaminic. Results indicated that the folded conformation remains of low energy not only in vacuo but also in water solution [128]. 

Fig. 2. Wave functions and energy levels for the solvated electron in (a) methylamine (MeA) and (b) hexamethylphosphoramide (HMPA). The potential V(r) and wavefunction are based upon the model of Jortner (101) and computed using values of the optical and static dielectric constants of the two solvents. The optical absorption responsible for the characteristic blue color is marked by h v and represents transitions between the Is and 2p states. The radius of the cavity is 3 A in MeA, and —4.5 A in HMPA. 

Our canvas here is to provide a qualitative description of current models for the NM-M transition, developed for both metal-ammonia and metal-methylamine solutions. For this purpose we also draw upon interpretations from other systems in which the transition from localized to itinerant electron regimes is well recognized (78). 

The MPE/MCSCF approach has been employed to study the interplay of solvent and conformation effects on the spin-spin coupling constants in methanol and methylamine [72], The simulated solvent effects are noticeable for the one-bond coupling constants and for some of the geminal coupling constants but negligible for 3/ee. The dielectric continuum effects have been found to depend considerably on the molecular conformation in the case of and 27ece. It is worth noting here that the MCSCF results have confirmed the conclusions drawn in ref. [80] from semi-empirical continuum model calculations. 

Computational approach. Lee and Houk conducted calculations using a methyl-ammonium ion to mimic the key lysine of the enzyme active site.16 They chose this model because, even though no crystal structures had been solved at the time, a lysine was known to be essential for catalysis.60 The reaction of orotate + CH3NH3 to form a carbene-methylamine complex was thus examined in various dielectrics using the SCI-PCM SCRF method in Gaussian 94.30 31 48 Solvation energies computed at the RHF/6-31 + G level were used to correct gas phase MP2/ 6-31 + G energies and obtain AH values for reaction in solution. 

Results. Lee and Houk were the first to model part of the ODCase active site when they calculated decarboxylation energetics for orotate in the presence of methylammonium ion as a mimic of the key active site lysine. Based on their conclusion that 4-protonation is an energetically favorable pathway (see above), they calculated the energy of reaction of orotate (la) plus Cf NHj to form a carbene-methylamine complex plus C02 (equation 1). 

Several different models of the active site were used, based on the reported crystal structures. In these, the OMP substrate (Scheme 1) was generally modeled as 1-methylorotate (lb), but in some calculations, parts of the ribose ring were also included. Lysine residues were modeled as methylamine, aspartate residues were... 

Results. Siegbahn and coworkers considered three mechanisms direct (C6)-protonation (mechanism v, 1 — 10, Scheme 2), 02-protonation (mechanism ii, 1 — 4 — 5, Scheme 2), and 04-protonation (mechanism iii, 1 — 6 — 7, Scheme 2).59 The direct protonation mechanism was calculated using several different models of the active site wherein some combination of methylamines, aspartates, and/or water was used. The lowest barriers were found for models that involve chains of residues spanning the methylammonium involved in protonating C6 and either 02 or 04 (for example, 14). 

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