A restricted Hartree-Fock SCF calculation was performed using Pulay DIIS with geometric direct optimization to evaluate the free energy of reaction in the solution according to Figure.1, where ΔE_solv_cr and ΔE_solv_or are the free energies of open- (or) and closed- ring (cr) conformation of midazolam in water and gas phase. The results indicate that the cr conformation has a better gas/water phase transition than the cr form. The energy of or-to-cr transition in either gas or water phase is negative indicating a direction of the chemical reaction at pH from 2.5 to 5.5, respectively.
I appreciate any comments on the subject.
Hi,
I am not sure what you are asking and judging from the lack of responses other are too? If you change the pH you change the "microstructure" or the molecule that you need to consider. You also change the solvent polarity. Please elaborate your question.
Best,
Peter
Hi, Peter. What would be the total charge of midazolam open/close ring at pH of 2.5 and 7.36? I used the neutral molecule to calculate the free energy of solvation. Thank you.
I do not know. You can download Marvin Beans for free and use their pka predictor tool to figure that kind of thing out. Its highly approximate, but its better than guessing. :) You can then follow that up with calculations of the protonated species and get the pkas yourself from ab initio level. A simple search on google can give you the procedure for that, not dissimilar to calul;ating solvation effects.
Best,
Peter
I did the total charge calculations using the Marvin Beans (pKa) software and Henderson-Hasselbalch equation (degree of dissociation) for midazolam open/close ring at physiological pH (7.36) as represented below. The net charges for both molecules tend to be mild positive or neutral, such as 0.41 and 0.0 for the open and close form of midazolam, respectively.
The net charge for midazolam open/close ring form was assessed considering the shape of the alpha distribution of functional groups for molecular macrospecies (%) at different pH according to the graphs shown below.
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