Solvation of Methyl Lactate in Water: Molecular Dynamics Studies

Subscriber access provided by READING UNIV

Article

Solvation of Methyl Lactate in Water : Molecular Dynamics Studies Sourav Palchowdhury, and Billenahally L. Bhargava J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.7b12248 • Publication Date (Web): 24 Jan 2018 Downloaded from http://pubs.acs.org on February 1, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

The Journal of Physical Chemistry B is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Physical Chemistry

Solvation of Methyl Lactate in Water : Molecular Dynamics Studies

Sourav Palchowdhury and B. L. Bhargava∗ School of Chemical Sciences, National Institute of Science Education & Research Bhubaneswar, HBNI P.O. Jatni, Khurda, Odisha - 752050, India.

∗ To whom correspondence should Email:[email protected] (B.L.B.)

be

addressed.

ACS Paragon Plus Environment

1

Phone:

+91-674-249-4160.

The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 28

Abstract: Methyl lactate (ML), a chiral α-hydroxy ester has been probed widely to understand the competition between two intramolecular H-bonds in solvents of different polarity. Recent experimental and high level quantum chemical studies have revealed the predominant existence of ML–water insertion complexes over addition complexes in aqueous solution. Although the stability of monohydrate insertion conformer was studied accurately, ab initio quantum chemical calculations failed to predict the most stable dihydrate conformer in analogy with the experimental spectroscopic search. Atomistic molecular dynamics simulations of aqueous solution of methyl lactate, predicts that the population and lifetime of different H-bonded ML–water addition complexes are dictated by their interaction energies. Although the population of dihydrate insertion complexes is higher than that of the monohydrate complexes, the lifetime of the former is smaller than the latter which is in good agreement with the experimental result. The nature of intramolecular H-bonds within a methyl lactate molecule in aqueous solution is opposite to that in the gas phase due to the solvation process in water by intermolecular H-bonding interactions.


2

Page 3 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1

Introduction

Hydrogen bonding, being ubiquitous in structural chemistry and biology, plays an important role in molecular recognition due to its unique properties. The structure and dynamics of complex biomolecular systems are greatly influenced by subtle balance between inter- and intramolecular hydrogen bonding. For example, protein folding and aggregation in solution are largely governed by the competition between inter- and intramolecular H-bonding interactions.1 Homochirality, a phenomenon where a substance exists in the same chiral form of its constituent molecules (enantiomer) such as amino acids and sugars, is ubiquitous in biological systems and is of great interest to the scientific community of modern time research.2, 3 Chiral recognition and chiral selection are proved to be the most important underlying mechanisms of homochirality.4, 5 Chiral recognition is greatly influenced by water solvation and desolvation processes6, 7 as well as by the delicate competition between intraversus intermolecular H-bonding interactions.8, 9 Bifunctional molecules with intramolecular H-bond are the model systems to understand this competition between intraversus intermolecular H-bonding interactions in liquid phase. The intramolecular Hbond of the bifunctional molecule can be disturbed10–12 or preserved13, 14 upon complex formation with the solvent molecules, based on the strength of internal H-bond as well as the size of the inserted solvent molecule. Presence of strong intramolecular H-bonds and aggregation induced H-bonding isomerism in α-Hydroxyesters have made them an automatic choice as prototype of molecular systems for investigating such phenomenon.15 Methyl lactate (ML), a relatively simple molecule, has been probed to study the competition between two different kinds of intramolecular Hbonding interactions where the hydroxyl group can be H-bonded either to carbonyl oxygen atom or to ester oxygen atom. Rotational and vibrational absorption spectrum as well as high level ab initio quantum chemical calculations have confirmed that the conformer having intramolecular H-bonding between hydroxyl group and ACS Paragon Plus Environment

3


Page 4 of 28

carbonyl oxygen of ML molecule to be the most stable in gas phase.16, 17 Fourier transform infrared (FTIR) and vibrational circular dichroism (VCD) spectroscopy have also shown the existence of similar kind of intramolecular H-bonding interactions in the liquid phase of ML.18, 19 Recently, FTIR jet spectroscopic studies on chiral recognition of ML identified the existence of binary, ternary and quaternary clusters of ML in gas phase.20 Hydrogen bonding interactions between water and chiral molecules lead to the solvation processes in aqueous environments, where most biological phenomena take place.21 Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra derived from solution phase experiments and gas phase ab initio quantum chemical calculations of ML with water molecules have proved significant transfer of chirality from the chiral solute to the achiral water molecules.22, 23 The study revealed the contribution of larger ML–(H2 O)n complexes (n > 1) in the VCD spectral band. Broadband chirped pulse and a cavity based microwave spectroscopic studies have also confirmed that more compact hydrated insertion complexes have greater stability than addition complexes. It has also been reported that although ab initio quantum chemical calculations can correctly predict the most stable monohydrate insertion conformer, it failed to predict the dihydrate one24 in analogy with the experimental spectroscopic search. Nevertheless, this relative population and stability between addition and insertion complexes depend on experimental condition induced kinetic and thermodynamic parameters. Herein, we report the observations from all atom classical molecular dynamics simulations of ML in water. In the present manuscript, we will discuss the competition between different types of intra- and intermolecular H-bonding interactions found in the aqueous solution of ML. We will particularly focus on the population and lifetime of monohydrate and dihydrate insertion complexes. Besides, a detailed analysis of the solution structure will be presented. To the best of our knowledge, ACS Paragon Plus Environment

4

Page 5 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


this is the first molecular dynamics study to shed light on the structure and dynamics in aqueous solution of an α-Hydroxyester.

2

Methodology and Simulation Details

All atom molecular dynamics (MD) simulations have been performed on a system of methyl lactate dissolved in water. We have used LAMMPS software25 to get the phase space information and VMD26 for the visual analysis of the trajectory and rendering images. The all atom force field parameters are taken from the PLAFF3 set of parameters particularly developed for molecular simulation of polylactide by Bruce and coworkers.27 The PLAFF3 set of parameters is based on a combination of OPLS and CHARMM force fields. The simple point charge model (SPC/E) has been used to model water molecules.28 The stretching and bending interactions in water molecules and the H-X bonds and H-X-H angles (where X is either carbon or oxygen) of ML molecule were constrained using SHAKE29 algorithm. The initial configuration was generated by fusing a cubical box consisting of 100 uniformly distributed methyl lactate molecules with a water box having same dimension. Water molecules with any of their atom coordinates falling within 2.0 ˚ A of any atom of methyl lactate molecule were discarded to remove bad overlap of coordinates. The final configuration consisting of 100 uniformly distributed methyl lactate molecules and 11000 randomly distributed water molecules was equilibrated in isothermalisobaric ensemble (constant NPT) for 2 ns at 300 K and 1 atmospheric pressure followed by the production run in a canonical ensemble condition (constant NVT) for 30 ns in a cubical box having side length of 70.203 ˚ A along each dimension. 13.0 ˚ A cutoff is used to calculate the non-bonded interactions. Long range electrostatic interactions30 were handled using particle-particle particle-mesh solver (PPPM). A timestep of 1.0 fs has been used to integrate the equations of motion. The temperature and pressure was controlled using Nóse-Hoover thermostat and barostat ACS Paragon Plus Environment

5


Page 6 of 28

with time constants of 1000.0 and 500.0 fs respectively. Three dimensional periodic boundary conditions were used. The atomic positions were stored at an interval of 5 ps. A schematic of a methyl lactate molecule showing all of its atom types are presented in the Figure 1.

Figure 1: Schematic of methyl lactate molecule with its atom types. CT, CL, CE and CA correspond to methyl, α carbon attached to the hydroxyl group, carbonyl carbon and alkoxy carbon atoms respectively. OL, OE and OA indicate hydroxyl, carbonyl and alkoxy oxygen atoms respectively. HT, HL and HA represent hydrogen atoms attached to CT, OL and CA atoms respectively.

3 3.1

Results and Discussion Hydrogen Bonding

In the present work, we have adapted the geometric criteria31 to classify H-bonds. A H-bond is defined as strong when the H atom and the acceptor are separated by a distance of less than 2.2 ˚ A and the angle made by the donor, H atom, and the acceptor falls within the range of 130-180◦ . The corresponding distance range and angular range are 2.0-3.0 ˚ A and 90-180◦ , respectively, for a weak H-bond. In the methyl lactate molecule, all the three distinct types of oxygen atoms (OL, OA and OE) can act as H-bond acceptors whereas only the hydroxyl oxygen atom (OL) can act as a H-bond donor. The water oxygen atom can behave both as a Hbond donor and H-bond acceptor. In aqueous solution of methyl lactate, both the intermolecular (between ML and H2 O) and intramolecular (within ML itself) H-bonded interactions are observed. In the following sections, we have analyzed ACS Paragon Plus Environment

6

Page 7 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


the time and ensemble average of different types of H-bonds as well as their lifetime stability. The fluctuations in hydrogen-bond populations with time are characterized by the time autocorrelation function (TCF)32 N 1 X hhij (t) · hij (0)i CHB (t) = N ij=1

(1)

where hij (t), an instantaneous hydrogen-bond operator takes the value 1 if molecules i and j are H-bonded at time t, and 0 otherwise, assuming the intermittent approximation.33, 34 The function CHB (t) gives the probability that the molecules i and j are H-bonded at time t, given that they were H-bonded at time 0. 3.1.1

Intermolecular ML–H2 O H-bonding

We have computed average number of total H-bonding interactions with water around a ML molecule as well as around different H-bonding sites (HL, OL, OA and OE) of a ML molecule. The average number of total ML–H2 O H-bonding interactions is calculated to be 5.45 whereas the numbers are 1.20, 2.0, 0.61 and 1.70 around HL, OL, OA and OE atoms, respectively for a single methyl lactate molecule. The interaction energy between a ML and H-bonded H2 O molecules is calculated by taking the difference between the energies of isolated species and their assembly. In an N -object system, the many-body interaction energy is calculated by the generalized equation ∆Eint = E(1, 2, ..., i, ..., N ) −

X

Ei

(2)

i

where ∆Eint is the N -body interaction energy, E(1, 2, ..., i, ..., N ) is the energy of the N -object system and Ei is the individual energy of the i-th species. The interaction energy between two molecular species consists of non-bonded LJ and coulombic energy terms ∆Eint =

XX i

j

(

4ǫij

"

σij rij

12

−

σij rij


7

6 #

1 qi qj − 4πǫ0 rij

)

(3)


Page 8 of 28

The interaction energies between a water molecule and ML are calculated to be -3.17 kcal-mol−1 , -3.49 kcal-mol−1 , -1.26 kcal-mol−1 and -2.43 kcal-mol−1 for the H-bonding interactions at HL, OL, OA and OE atoms respectively. We can observe that the average number of ML–H2 O H-bonds at three different acceptor sites (OL, OA and OE) of a ML molecule follow the same trend of ∆Eint , i. e., more negative the interaction energy is, more the number of intermolecular ML–(H2 O) H-bonding interactions. The average number of ML–H2 O H-bonds and corresponding interaction energies at different H-bonding sites of ML are tabulated in Table 1. To

Table 1: Average number of ML–H2 O H-bonds and corresponding interaction energies at different H-bonding sites of ML Site Average number ∆Eint (kcal-mol−1 ) of H-bonds HL 1.20 -3.17 OL 2.0 -3.49 OA 0.61 -1.26 OE 1.70 -2.43

explore the three dimensional arrangement of H-bonded water molecules around a ML molecule at different H-bonding sites, we have presented the probability distribution of the angle between the normal vector of the molecular plane of a ML molecule (constructed by CL, CE and OA atoms) centered at the CE site and the vector joining the oxygen atom of the H-bonded water molecule and CE in Figure 2. For H-bonded water molecules at OA and OE sites, the water oxygen atoms show slightly higher preference to stay in the molecular plane whereas with HL site, they are preferentially located above and below the molecular plane. H2 O molecules Hbonded with OL atom are more likely to be present at an angle of about 60◦ with respect to the molecular plane. In Figure 3, the spatial distribution function of water oxygen atoms around a methyl lactate molecule also confirms the preferential accumulation of water molecules above and below the molecular plane of ML ACS Paragon Plus Environment

8

Page 9 of 28

3

HL OL OA OE

2

P(cosθ)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1

0 -1

-0.5

0

0.5

1

cos(θ) Figure 2: Probability distribution of angle between the normal vector of the molecular plane of a ML molecule centered at the CE and the vector joining the oxygen atom of the H-bonded water molecule and CE. molecule. The isosurface density of water oxygen atoms (in yellow) corresponds to 2 times their average density. A snapshot of a methyl lactate molecule surrounded by H-bonded water molecules is presented in Figure 4 which clearly shows that water oxygen atoms are mostly located above and below the molecular plane of the methyl lactate molecule. Figure 5 shows the time evolution of CHB (t) for intermolecular ML–H2 O H-bonds formed at different H-bonding sites of methyl lactate molecule. The computed TCFs are fitted to a stretched exponential decay function35 CHB (t) = exp(−(t/τHB )β )

(4)

where τHB is the residence time associated with the exponential function and β stands for stretched exponent.The fitted parameters are listed in Table 2. It is evident from the Figure 5 and Table 2 that the lifetime of intermolecular ML–H2 O ACS Paragon Plus Environment

9


Page 10 of 28

Figure 3: Spatial density of water oxygen atoms (yellow) around the methyl lactate molecule.

Table 2: Parameters of the stretched exponential fit to the survival time autocorrelation function, CHB (t), for intermolecular H-bonds between water and different H-bonding sites of ML. Site HL OL OA OE

τHB (ps) 3.66 4.63 0.18 1.70

β 0.60 0.60 0.30 0.47

H-bonds at four different sites of methyl lactate molecule follow the same trend of stabilizing interaction energy of the ML–H2 O H-bonded complex. In other words, more negative the interaction energy of ML–H2 O H-bonded complex, higher will be the lifetime of corresponding ML–H2 O H-bonded interaction.


10

Page 11 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 4: Snapshot of a methyl lactate molecule surrounded by H-bonded water molecules 3.1.2

ML–(H2 O)m Cluster Analysis

We have observed the formation of both the dihydrate ML–(H2 O)2 and monohydrate ML–(H2 O) H-bonded insertion complexes in the aqueous solution of methyl lactate. We have defined a monohydrate ML–(H2 O) complex as one where the water molecule is simultaneously involved in H-bonding interactions with the hydroxyl group and either of the OA or OE atom of a ML molecule. A dihydrate ML–(H2 O)2 cluster is the assembly where a single water molecule (termed as the “first”) is showing simultaneous H-bonding interactions with the hydroxyl group of ML and a second water molecule (termed as the “second”) while the second water molecule is Hbonded to either of the OA or OE atom of the same ML molecule. Our definition of an insertion complex is slightly relaxed with respect to the previous definition22 ACS Paragon Plus Environment

11


1

HL OL OA OE

0.8

CHB(t)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 28

0.6 0.4 0.2 0 0

25

50

75

100

Time (ps) Figure 5: Survival autocorrelation function, CHB (t) for intermolecular ML–H2 O H-bonds formed at different H-bonding sites of methyl lactate molecule. where presence of intramolecular H-bonding interactions in a ML molecules was also taken as a constraint. In the solution, exclusively insertion complexes, addition complexes or mixed insertion–addition ML–water complex can exist. 32% of ML molecules (i.e., 32 out of 100 ML molecules present in the system) in their aqueous solution exists as monohydrate ML–(H2 O) insertion complexes in which 18% involves H-bonding interaction between water and OA atom and 14% involves H-bonding interaction between water and OE atom. The average interaction energy for two types of ML–(H2 O) complexes are calculated to be -2.98 kcal-mol−1 and -3.52 kcal-mol−1 for the H-bonding interactions at OA and OE atoms, respectively. We have found that on an average, 55% of methyl lactate molecules are involved in the formation of ML–(H2 O)2 type dihydrate insertion complexes among which 31% and 24% are the populations where the second water molecule is HACS Paragon Plus Environment

12

Page 13 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


bonded to OE and OA, respectively. The average interaction energy for these two types of ML–(H2 O)2 complexes are calculated to be -8.17 kcal-mol−1 and -7.44 kcalmol−1 when the second water molecule is H-bonded to the OE and OA atoms, respectively which is in good agreement with their corresponding population. Again, more stabilizing ∆Eint for either of the two types of ML–(H2 O)2 dihydrate insertion complexes compared to ML–(H2 O) monohydrate insertion complexes leads to greater population of the former than the latter in the aqueous solution of methyl lactate. Among these 31% of population where the second water molecule is H-bonded to OE, H-bonding interaction of the first water molecule with OE exists in 18% of cases (monohydrate insertion complex) whereas it is only 2% for H-bonding interaction between the first water molecule and OA (monohydrate insertion complex). On the other hand, among 24% of ML–(H2 O)2 complexes having H-bonding interaction between the second water molecule and OA, 15% of cases show H-bonding interaction between first water molecule and OA (monohydrate insertion complex) whereas only 1% population is found to have H-bonding interaction between first water molecule and OE (monohydrate insertion complex). Overall, the population of ML–(H2 O) monohydrate insertion complexes arising from ML–(H2 O)2 dihydrate insertion complexes is negligible in the solution, i.e., there are very few ML dihydrate complexes which can also be considered as monohydrate complexes. Figure 6 depicts the probability distribution of angle between the normal vector of the molecular plane of a ML molecule centered at the CE and the vector joining the oxygen atom of the H-bonded water molecule in different ML–(H2 O)m and CE. We can observe that the oxygen atom of the first water molecule (H-bonded to OE) in ML–(H2 O)2 shows a high degree of preference to be located above and below the molecular plane of ML whereas this probability is less pronounced in remaining three cases. The water molecule in the monohydrate ML–(H2 O) insertion complex H-bonded to OE shows slightly greater probability to be located above and below the ML plane. Figure 7 presents ACS Paragon Plus Environment

13


4

3

P(cosθ)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 28

2

ML-H2O (OA) ML-H2O (OE) ML-(H2O)2 (First-OA) ML-(H2O)2 (First-OE) ML-(H2O)2 (Second-OA) ML-(H2O)2 (Second-OE)

1

0 -1

-0.5

0

0.5

1

cosθ Figure 6: Probability distribution of angle between the normal vector of the molecular plane of a ML molecule centered at the CE and the vector joining the oxygen atom of the H-bonded water molecule in different ML–(H2 O)m and CE. the snapshots of monohydrate insertion complexes when water molecule (yellow) is (a) H-bonded to OA (b) H-bonded to OE and dihydrate insertion complexes when the second water molecule (red) is (c) H-bonded to OA and (d) H-bonded to OE. The orientational order parameter q has been computed to study the local structural order of water molecules inserted into the ML–(H2 O)m frameworks. The order parameter is given by36, 37 q=

2 3 4 3X X 1 1− cos ψjk + 8 j=1 k=j+1 3

(5)

where ψjk is the angle formed by the vectors joining the oxygen atom of a given water molecule and those of its four nearest neighbors j and k. The h· · · i means that q is averaged over all the water molecules. The values of q is in the range −3 ≤ q ≤ 1. In a perfect tetrahedral arrangement, q=1 whereas for a random molecular arrangement, as in an ideal gas, the mean value of q vanishes. The value ACS Paragon Plus Environment

14

Page 15 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 7: Snapshots of monohydrate insertion complexes when water molecule (yellow) is (a) H-bonded to OA (b) H-bonded to OE and dihydrate insertion complexes when the second water molecule (red) is (c) H-bonded to OA and (d) H-bonded to OE. of q ≪ 0 corresponds to unrealistic arrangement of molecules. Thus, q is a measure of the degree of tetrahedrality in the arrangement of four nearest neighbors around a central one. The tetrahedral order parameter, q, around different water molecules in dihydrate ML–(H2 O)2 insertion complexes is shown in figure 8. From the figure, one ACS Paragon Plus Environment

15


can notice that the most probable value of q is ∼0.60 in all the four cases (around the first and second water molecule when the second water is either H-bonded to OA or OE). We can observe that the probability at the most probable value of q is highest

0.02

0.015

P(q)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 28

First (OA) First (OE) Second (OA) Second (OE)

0.01

0.005

0 -1

-0.5

0

q

0.5

1

Figure 8: Probability distribution of the tetrahedral order parameter around the first and second water molecule in a dihydrate ML–(H2 O)2 insertion complex when the second water molecule is either H-bonded to OA or OE (represented within the parenthesis). around the first water molecule when the second water molecule is H-bonded to the OE atom and least around the second water molecule when it is H-bonded to OA. The rest of the two events show similar probability at the most probable value of q. Water molecule inserted into the monohydrate ML–(H2 O) skeleton shows similar profile of orientational order as the first water molecule in dihydrate ML–(H2 O)2 insertion complex (not shown here). The calculated time evolution of CHB (t) for monohydrate ML–(H2 O) and dihydrate ML–(H2 O)2 insertion complexes of different types in Figure 9 shows that ACS Paragon Plus Environment

16

Page 17 of 28

the TCFs for both types of monohydrate insertion complexes decay at a slower rate than the TCFs for dihydrate insertion complexes. The mean lifetimes (τHB ) have

1

ML-H2O (OA) ML-H2O (OE) ML-(H2O)2 (OA) ML-(H2O)2 (OE)

0.8

CHB(t)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


0.6 0.4 0.2 0 0

5

10

15

20

25

30

Time (ps) Figure 9: Survival autocorrelation function, CHB (t) for monohydrate and dihydrate insertion complexes of methyl lactate molecules in aqueous solution. been evaluated from the time integral of CHB (t)34 τHB =

Z

∞

CHB (t)dt

(6)

0

The mean lifetimes τHB for different types of monohydrate and dihydrate insertion complexes of methyl lactate molecule are listed in Table 3. Due to the greater mean lifetime (τHB ) of monohydrate insertion complexes compared to the dihydrate insertion complexes (Table 3), former ones are encountered more frequently compared to latter ones in the experimental observation.22 The lesser lifetime of a dihydrate insertion complex than the monohydrate insertion one is due to the smaller lifetime of the second water molecule than the first one in both of the dihydrate insertion ACS Paragon Plus Environment

17


Table 3: Mean lifetimes (τHB ) for different types of monohydrate and dihydrate insertion complexes of methyl lactate molecule. Type

τHB (ps) ML–(H2 O) (OA) 1.28 ML–(H2 O) (OE) 0.91 ML–(H2 O)2 (OA) 0.57 ML–(H2 O)2 (OE) 0.58

complexes as evidenced from the Figure 10. The mean lifetime τHB for the first

1

First (OA) First (OE) Second (OA) Second (OE)

0.8

CHB(t)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 18 of 28

0.6 0.4 0.2 0 0

10

20

30

40

Time (ps) Figure 10: Survival autocorrelation function, CHB (t) for first and second water molecule in dihydrate insertion complex of different types for methyl lactate molecule in aqueous solution. water molecule in a ML–(H2 O)2 type of dihydrate insertion complex are 1.018 ps and 1.230 ps whereas the values for the second water molecule are 0.930 ps and 0.980 ps when the second water molecule is H-bonded to the OA atom or OE atom, ACS Paragon Plus Environment

18

Page 19 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


respectively. 3.1.3

Intramolecular H-bonding in ML

Chiral recognition process crucially depends on competition between intra- and intermolecular H-bonding interactions. In aqueous solution, 48% and 29% of ML molecules are involved in the formation of OL–HL· · · OA and OL–HL· · · OE intramolecular H-bonding interactions respectively. There are more ML molecules in which OA atoms are involved in intramolecular H-bond formation, which is opposite to the observed preference in gas phase.16 In the gas phase, we have found that the probability of formation of OL–HL· · · OE intramolecular H-bond is 48% whereas it is 24% for the OL–HL· · · OA intramolecular H-bond. The calculated energies based on OPLS–AA functional of a ML molecule in aqueous solution with intramolecular OL–HL· · · OA and OL–HL· · · OE H-bonds are 9.13 kcal-mol−1 and 9.86 kcal-mol−1 , respectively. The preference of an intramolecular OL–HL· · · OA over OL–HL· · · OE H-bonding interaction in aqueous solution can be attributed to the fact that compared to the OA atom, the OE atom of a ML molecule is preferentially involved in the formation of intermolecular H-bonding with water molecules (Table 1 and Table 2) and hence, less available for the formation of OL–HL· · · OE intramolecular H-bonds. 22% and 42% of ML molecules which exist as monohydrate and dihydrate complex, respectively, are also found to exhibit intramolecular H-bonding. We have seen that in monohydrate insertion complexes, OA or OE which acts as the H-bond acceptor from the water also shows preference to act as the intramolecular H-bond acceptor. Similarly, in dihydrate insertion complexes, OA or OE acting as the Hbond acceptor from the second water molecule shows preference to function as the H-bond acceptor in the intramolecular H-bond framework. Table 4 provides the population of intramolecular H-bonds in various insertion complexes. The formation of intramolecular H-bonding interaction has considerable effect on the tetrahedral order parameter at the OE. Figure 11 presents the orientational ACS Paragon Plus Environment

19


Table 4: Population (%) of intramolecular H-bonds in different insertion complexes Type ML–H2 O(OA) ML–H2 O(OE) ML–(H2 O)2 (OA) OL–HL· · · OA 9.5% 3.62% 14.6% OL–HL· · · OE 3.27% 6.42% 4.3%

ML–(H2 O)2 (OE) 8.7% 14.6%

order parameter profile at the OA and OE atoms of ML molecule in three different cases of intramolecular H-bonding interactions (OL–HL· · · OA, OL–HL· · · OE and no intramolecular H-bonding). The most probable value of q around OA is 0.52 in

0.015

0.01

P(q)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 20 of 28

OA (Intra HL-OA) OE (Intra HL-OA) OA (Intra HL-OE) OE (Intra HL-OE) OA (Intra absent) OE (Intra absent)

0.005

0 -1

-0.5

0

q

0.5

1

Figure 11: Probability distribution of the tetrahedral order parameter around OA and OE atoms of a ML molecule in three different cases of intramolecular H-bonding interactions (OL–HL· · · OA, OL–HL· · · OE and no intramolecular H-bonding) in aqueous solution. all the three cases whereas the values are 0.30, 0.40 and 0.46 around the OE atom, respectively, for the events of intramolecular OL–HL· · · OA H-bonding, absence of intramolecular H-bonding and intramolecular OL–HL· · · OE H-bonding interactions. ACS Paragon Plus Environment

20

Page 21 of 28

Clearly, the orientational ordering of nearest four oxygen atoms capable of forming H-bonds around the OE atom is more in the case of intramolecular OL–HL· · · OE H-bond. Figure 12 presents the time evolution of CHB (t) for intramolecular OL–HL· · · OA and OL–HL· · · OE H-bonds both in aqueous and gas phase. We observe a sharp fall

1

HL-OA (Aqueous) HL-OE (Aqueous) HL-OA (Gas) HL-OE (Gas)

0.8

CHB(t)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


0.6 0.4 0.2 0 0

10

20

30

40

50

Time (ps) Figure 12: Survival autocorrelation function, CHB (t) for intramolecular OL– HL· · · OA and OL–HL· · · OE H-bonds in aqueous and gas phase. in all the time correlation functions (TCFs) during first 3 ps followed by a steady fall at larger observation time. We see that the H-bonds are long lived over a larger observation time. The lifetimes for the OL—HL· · · OA H-bonds in aqueous phase and OL—HL· · · OE H-bonds in gas phase have only decayed up to 50% over a larger observation time. On the other hand, the lifetime for the OL—HL· · · OE H-bonds in aqueous phase has been decayed up to 72% whereas the decay is ∼78% for the OL—HL· · · OA H-bonds in the gas phase. From figure 12, one can notice that OL– HL· · · OA H-bond is more stable in aqueous phase compared to the other whereas ACS Paragon Plus Environment

21


Page 22 of 28

OL–HL· · · OE H-bond is more stable in gas phase. We can also observe that the intramolecular OL–HL· · · OA H-bonds have greater survival probability than the other one in the solution phase while the trend is opposite in the gas phase.

4

Conclusions

We have carried out atomistic molecular dynamics simulations on a system of methyl lactate dissolved in water with the primary objective of investigating the population and lifetime of different types of intramolecular H-bonding interactions in a methyl lactate molecule and intermolecular H-bonded ML–water complexes formed in the aqueous solution. We have found that the population and lifetime of H-bonded ML– water addition complexes at different sites of a methyl lactate molecule are governed by the stabilizing interaction energy between the methyl lactate molecule and the corresponding H-bonded water molecule. Water molecule H-bonded to a methyl lactate molecule shows preference to be oriented above and below the molecular plane of methyl lactate molecule as evidenced from the spatial distribution functions. We have encountered formation of monohydrate ML–(H2 O) and dihydrate ML–(H2 O)2 insertion clusters in the aqueous solution of methyl lactate. Among 32% ML–(H2 O) monohydrate insertion complexes, the population arising due to H-bonding interaction between water and ester oxygen atom of methyl lactate is more than the clusters having H-bonding interaction between water and carbonyl oxygen atom of methyl lactate. Among the insertion complexes of methyl lactate, ML–(H2 O)2 dihydrate insertion complexes are found to be dominant. Dihydrate insertion complexes having intermolecular H-bond between the second water molecule and the carbonyl oxygen of methyl lactate are populated more than the dihydrate insertion complexes having intermolecular H-bonding interaction between the second water molecule and the ester oxygen atom of methyl lactate. The monohydrate insertion complexes are observed to have longer lifetimes than the dihydrate ones which is in good agreement ACS Paragon Plus Environment

22

Page 23 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


with the experimental finding. The lifetime of a dihydrate insertion complex is governed by the lifetime of the second water molecule of the corresponding cluster. The tetrahedral order parameter for the water molecules inside the dihydrate insertion complexes depends on the H-bond acceptor site of methyl lactate molecule. Methyl lactate molecules show high preference to exhibit intramolecular H-bonding in their aqueous solution. The probability to find an intramolecular H-bond formed between the hydroxyl hydrogen atom and ester oxygen atom of a methyl lactate molecule is almost double than the probability of formation of intramolecular H-bond between the hydroxyl hydrogen atom and carbonyl oxygen atom of methyl lactate molecule, which is opposite to that observed in the gas phase. Such a preference is attributed to the availability of the acceptor oxygen atom to form the intramolecular H-bonds.

Acknowledgments The authors gratefully acknowledge NISER, Bhubaneswar for providing the computational facilities.

References [1] Jackson, M.; Mantsch, H. H. Beware of Proteins in DMSO. Biochim. Biophys. Acta 1991, 1078, 231-235. [2] Mason, S. F. Origins of Biomolecular Handedness. Nature 1984, 311, 19-23. [3] Blackmond, D. G. The Origin of Biological Homochirality. Cold Spring Harb. Perspect. Biol. 2010, 2, a002147. [4] Breslow, R. A Likely Possible Origin of Homochirality in Amino Acids and Sugars on Prebiotic Earth. Tetrahedron Lett. 2011, 52, 2028-2032. [5] Meyer, V. R.; Rais, M. A Vivid Model of Chiral Recognition. Chirality 1989, 1, 167-169. ACS Paragon Plus Environment

23


Page 24 of 28

[6] Levy, Y.; Onuchic, J. N. Water Mediation in Protein Folding and Molecular Recognition. Annu. Rev. Biophys. Biomol. Struct. 2006, 35, 389-415. [7] Zehnacker, A.; Suhm, M. A. Chirality Recognition Between Neutral Molecules in the Gas Phase. Angew. Chem. Int. Ed. 2008, 47, 6970-6992. [8] Seurre, N.; Barbu-Dbus, K. L.; Lahmani, F.; Zehnacker, A.; Borho, N.; Suhm, M. A. Chiral Recognition Between Lactic Acid Derivatives and an Aromatic Alcohol in a Supersonic Expansion. Phys. Chem. Chem. Phys. 2006, 8, 10071016. [9] Borho, N.; Suhm, M. A. Glycidol Dimer: Anatomy of a Molecular Handshake. Phys. Chem. Chem. Phys. 2002, 4, 2721-2732. [10] Imhof, P.; Roth, W., Janzen, C.; Spangenberg, D.; Kleinermanns, K. Hydrogenbonded Phenol-acid Clusters Studied by Vibrational Resolved Laser Spectroscopy and ab initio Calculations I. Formic Acid. Chem. Phys. 1999, 242, 141-151. [11] Imhof, P.; Roth, W., Janzen, C.; Spangenberg, D.; Kleinermanns, K. Hydrogenbonded Phenol-acid Clusters Studied by Vibrational Resolved Laser Spectroscopy and ab initio Calculations II. Acetic Acid. Chem. Phys. 1999, 242, 153-159. [12] Graham, R. J.; Kroemer, R. T.; Mons, M.; Robertson, E. V.; Snoek, L. C.; Simons, J. Infrared Ion Dip Spectroscopy of a Noradrenaline Analogue: Hydrogen Bonding in 2-Amino-1-phenylethanol and Its Singly Hydrated Complex. J. Phys. Chem. A 1999, 103, 9706-9711. [13] Barbu, K. L.; Lahmani, F.; Zehnacker-Rentien, A. Formation of HydrogenBonded Structures in Jet-Cooled Complexes of a Chiral Chromophore Studied


24

Page 25 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


by IR/UV Double Resonance Spectroscopy: Diastereomeric Complexes of (±)2-Napthyl-1-ethanol with (±)-2-Amino-1-propanol. J. Phys. Chem. A 2002, 106, 6271-6278. [14] Seurre, N.; Sepiol, J. Barbu-Debus, K. Le.; Lahmani, F.; Zehnacker-Rentien, A. The Role of Chirality in the Competition between Inter and Intramolecular Hydrogen Bonds: Jet-cooled van der Waals Complexes of (±)-2-Napthyl-1ethanol with (±)-1-Amino-2-propanol and (±)-2-amino-1-butanol. Phys. Chem. Chem. Phys. 2004, 6, 2867-2877. [15] Borho, N.; Suhm, M. A. Self-organization of Lactates in the Gas Phase. Org. Biomol. Chem. 2003, 1, 4351-4358. [16] Schrøder, S. D.; Wallberg, J. H.; Kroll, J. A.; Maroun, Z.; Vaida, V.; Kjaergaard, G. Intramolecular Hydrogen Bonding in Methyl Lactate. J. Phys. Chem. A 2015, 119, 9692-9702. [17] Borho, N.; Xu, Y. Rotational Spectrum of a Chiral α-hydroxyester: Conformation Stability and Internal Rotation Barrier Heights of Methyl Lactate. Phys. Chem. Chem. Phys. 2007, 9, 1324-1328. [18] Cassanas, G.; Morssli, M.; Fabregue, E.; Bardet, L. Vibrational Spectra of Lactic Acid and Lactates. J. Raman Spectrosc. 1991, 22, 409-413. [19] Bursi, R.; Devlin, F. J.; Stephens, P. J. Vibrationally induced ring currents? The Vibrational Circular Dichroism of Methyl Lactate. J. Am. Chem. Soc. 1990, 112, 9430-9432. [20] Fárn´ık M.; Weimann, M.; Steinbach, C.; Buck, U.; Borho, N.; Adler, T. B.; Suhm, M. A. Size-selected Methyl Lactate Clusters: Fragmentation and Spectroscopic Fingerprints of Chiral Recognition. Phys. Chem. Chem. Phys. 2006, 8, 1148-1158. ACS Paragon Plus Environment

25


Page 26 of 28

[21] Jeffrey, J. A.; Saenger, W. Hydrogen Bonding in Biological Structures; SpringerVerlag, Berlin, 1991. [22] Losada, M.; Xu, Y. Chirality Transfer Through Hydrogen-bonding: Experimental and ab initio Analyses of Vibrational Circular Dichroism Spectra of Methyl Lactate in Water. Phys. Chem. Chem. Phys. 2007, 9, 3127-3135. [23] Perera, A. S.; Thomas, J.; Poopari, M. R.; Xu, Y. The Clusters-in-a-Liquid Approach for Solvation: New Insights from the Conformer Specific Gas Phase Spectroscopy and Vibrational Optical Activity Spectroscopy. Front. Chem. 2016, 4, 9. [24] Thomas, J.; Sukhorukov, O.; Jáger, W.; Xu, Y. Direct Spectroscopic Detection of Free OH Groups in Methyl Lactate–(Water)1,2 Clusters: Hydration of a Chiral Hydroxy Ester. Angew. Chem. Int. Ed. 2014, 53, 1156-1159. [25] Plimpton, S. Fast Parallel Algorithms for Short-Range Molecular Dynamics. J. Comput. Phys. 1995, 117, 1-19. [26] Humphrey, W.; Dalke, A.; Schulten, K. VMD Visual-Molecular Dynamics. J. Mol. Graphics 1996, 14, 33-38. [27] McAliely, J.; Bruce, D. A. Development of Force Field Parameters for Molecular Simulation of Polylactide. J. Chem. Theory. Comput. 2011, 7, 3756-3767. [28] Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; Hermans, J. In Intermolecular Forces; Pullman, B., Ed.; Reidel: Dordrecht, The Netherlands, 1981; p 331. [29] Ryckaert, J. P.; Ciccotti, J.; Berendsen, H. J. C. Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes. J. Comput. Phys. 1977, 23, 327-341. ACS Paragon Plus Environment

26

Page 27 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


[30] Allen, M. P.; Tildesley, D. J. Computer Simulation of Liquids; Clarendon Press: Oxford, U.K., 1987. [31] Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond, In Structural Chemistry and Biology; Oxford University Press: New York, 2001. [32] Luzar, A.; Chandler, D. Hydrogen-Bond Kinetics in Liquid Water. Nature 1996, 379, 55-57. [33] E. Lloyd, Handbook of Applicable Mathematics. Volume II: Probability, Wiley, New York, 1st edn, 1980. [34] Eloa, M. D.; Ladanyi, B. M. Computational Study of Structural and Dynamical Properties of Formamide-Water Mixtures. J. Chem. Phys. 2006, 125, 184506184519. [35] Berberan-Santos, M. N.; Bodunov, E. N.; Valeur B. Mathematical Functions for the Analysis of Luminescence Decays with Underlying Distributions 1. Kohlrausch Decay Function (Stretched Exponential). Chem. Phys. 2005, 315, 171-182. [36] Chau, P. L.; Hardwick, A. J. A New Order Parameter for Tetrahedral Configurations. Mol. Phys. 1998, 93, 511-518. [37] Errington, J. R.; Debendetti, P. G. Relationship between Structural Order and the Anomalies of Liquid Water. Nature 2001, 409, 318-321.


27


TOC Graphic


28

Page 28 of 28

Solvation of Methyl Lactate in Water: Molecular Dynamics Studies

Recommend Documents