Carbohydrate and Trivalent Iron Ion Interactions in the Gas Phase and in Aqueous Solution - Metallic Systems: A Quantum Chemist's Perspective - page 86

identify. the. reactive. sites. of. methyl-α-mannopyranoside. toward. the. trivalent. iron.
ion.(Fe 3+ ).in.the.gas.phase.and.in.aqueous.solution.[39,40]..Calculations.of.a.chemi-
cal. reactivity. index. using. density. functional. theory. (DFT). and. simulations. using.
Car-Parrinello. molecular. dynamics. (CPMD). show. that. the. Fe 3+ . ion. preferentially.
interacts. with. speciic. hydroxyl. oxygen. atoms. of. the. carbohydrate.. These. predic-
tions. were. shown. to. be. in. accord. with. mass. spectrometric. measurements. [39,40]..
Furthermore,. CPMD. simulations. indicate. that. the. speciic. conformational. prefer-
ence. of. the. glycosidic. linkage. of. methyl-α-mannopyranoside. in. the. gas. phase. is.
inluenced.by.intramolecular.hydrogen.bonding.interactions.[39]..In.contrast,.CMD.
simulations. using. OPLS-AA. and. UFF. force. ields. for. the. carbohydrate. and. the.
metal.ion,.respectively,.converged.to.structures.that.differ.from.the.mass.spectrom-
etry. data,. suggesting. that. classical. molecular. simulations. are. insensitive. to. these.
effects.[39]..This.comparison.demonstrated.the.importance.of.chemical.reactivity.
calculations.and.CPMD.simulations.for.predicting.the.reactive.sites.of.a.biomolecule.
toward.metal.ions..In.addition,.we.used.this.integrated.approach.based.on.theoretical.
calculations,.molecular.simulations,.and.mass.spectrometric.measurements.to.study.
the.active.sites.of.methyl-α-mannopyranoside.toward.Fe 3+ .ions.in.aqueous.solution.
[40].. Again,. results. were. compared. to. those. obtained. via. CMD. simulations.. The.
insights. obtained. from. CPMD. simulations. are. consistent. with. the. chemical. reac-
tivity. calculations,. natural. partial. charge. analysis. (NPA),. and. mass. spectrometric.
measurements..Based.on.our.theoretical.studies.using.chemical.reactivity.calcula-
tions,.CPMD.simulations,.NPA,.and.Gibbs.free.energy.change.calculations,.we.are.
able.to.predict.the.structure,.conformation,.and.coordination.chemistry.of.methyl-
α-mannopyranoside.and.the.Fe 3+ .ion.in.the.gas.phase.and.in.aqueous.solution..Our.
studies. show. that. the. inclusion. of. the. solvent. medium. impacts. the. coordination.
chemistry.of.the.carbohydrate.with.the.Fe 3+ .ion.as.well.as.the.resulting.structure.and.
conformation.of.the.biometallic.compound.[40]..In.addition,.we.calculated.the.bind-
ing.afinities.of.the.Fe 3+ .ion.with.methyl-α-mannopyranoside.in.the.gas.phase.and.
in. aqueous. solution.. Results. obtained. from. our. calculations. and. simulations. were.
compared.to.experimental.measurements,.and.as.mentioned.above,.we.ind.that.the.
calculations.and.simulations.performed.at.the.ab.initio.level.agree.very.well.with.the.
experiments,.whereas.the.results.we.obtained.using.classical.molecular.simulations.
deviate.both.from.our.irst.principles.calculations.and.from.the.experiment..In.this.
chapter,.we.describe.the.theoretical.methods.used.in.these.studies.and.present.the.
results.obtained.for.methyl-α-mannopyranoside.and.its.complex.with.the.Fe 3+ .ion.in.
the.gas.phase.and.in.aqueous.solution..Our.studies.indicate.that.this.new.theoretical.
strategy.can.be.used.in.coordination.chemistry.studies.of.any.organic.compound.or.
biomolecule. with. metal. ions. and. is. not. limited. to. investigations. of. carbohydrates.
and.metal.ions..As.mentioned.above.and.presented.in.Section.3.2,.the.new.strategy.
yields.accurate.results.for.biometallic.species.not.only.in.the.gas.phase.but.also.in.
more.complicated.environments,.such.as.the.dense.aqueous.solution.environment.
3.2 METHODS
Detailed.description.of.the.methods.used.herein.is.provided.in.Chapter.2.