2.3 MD simulation
The most stable molecular configuration for E adsis obtained by MD annealing simulation. Implicit-solvent atomistic MD
annealing simulation are carried out at 1 K to 1800 K which can overcome
the rotational barrier in flexible molecules to search for conformation
in a wider range the number of annealing cycles is 4000, and the heating
and cooling ramps per cycle are 1038. The simulation
system is a 11.404 nm × 11.404 nm × 8.000 nm box. The COMPASSII force
field39 modeled the Van der Waals interaction and the
bonding interaction. The MD simulations were performed using an NVT
ensemble, and the thermostat is
Nose-Hoover40. All the simulation starts with the
structure of energy minimization and are carried out for 50 ps in the
NVT ensemble. Another 1000 ps MD annealing simulation was performed for
data collection at a frequency of 1 fs.
The
molecular
mechanics (MM) method41 was utilized to calculated theE ads between the designed
molecule
and the -OH decorated SiO2 surface. The Van der Waals
interaction and the bonding interaction are modeled by COMPASSII force
field 39 . The electrostatic interaction is
calculated by the Ewald summation method where the charges of each atom
are calculated by the charge equilibrium (QEq)
method42, 43.The Eads is calculated
by:
where ESiO2/designed,
ESiO2 and Edesignedmolecule are the energy of SiO2/designed
molecule complex SiO2 and designed molecule,
respectively.
The
implicit solvent model (εr = 78.5) is used to consider the solvation
effect38. The accuracy of Ewald summation is set as
10-5 kcal/mol, and the long-range tail of the Lennard
Jones potential is truncated at 1.85 nm with an extra 0.1 nm (cubic
spline method) to guarantee the smoothness of the potential function.
The system is considered to be equilibrium when the energy change is
lower than 2×10-5 kcal/mol, force lower than 0.01
kcal/mol/nm, and displacement lower than 10-6 nm.
Results and Discussion
3.1 Multi-scale molecular design and molecular simulation forrapid underwater adhesion
and long-term antifouling
The
tail chain, scaffold, and head group of target molecules have different
roles in practical applications. The tail chain is exposed to the water
environment and plays an antifouling effect. Related studies have
reported hydrophilic linear monomethoxy-terminated poly(ethylene glycol)
(mPEG)44, poly(sulfobetaine methacrylate)
(PSBMA)18 or poly(N,N-dimethylamino ethyl
methacrylate) (PDMAEMA)45 can play a good anti-protein
role in the aqueous environment. These three polymer segments are
designed in Molecules 1, 2, and 3 to compare hydration degrees. The
branching degree of the designed molecule will not only affect polymer
aggregation morphology in solution, but also determine the surface
electrostatic potential of the polymer molecule and the adsorption site
with the substrate46. Therefore, four designed
Molecules 1, 4, 5, and 6 were designed to be a single head-single tail,
a double head-double tail, a triple head-triple tail, and a quadruple
head-quadruple tail, corresponding to the branching degrees of one, two,
three, four. The conjugated scaffold connects the head group and the
tail chain and its rigidity plays a decisive role in polymer adhesion
configuration on the substrate surface. For this reason, soft and rigid
scaffolds with similar chemical groups were selected and designed as
Molecules 5, 7, 8, and 9 to consider their functions in the polymer. The
head group binds to various substrates in water to play an adhesion
role. The DOPA has been a powerful anchor for surface modification and
can adhere to virtually almost any material
surface47-49. So the DOPA will be selected to be the
main component of the head group, and its function will also be
confirmed through analyzing the designed Molecule 5, 10, 11, and 12. To
summarize, the optimal structure of the target polymer was screened by
adjusting the branching numbers of polymer molecules, changing the type
of head groups, tail chain, and scaffold. (Figure 1a ) In the
process of theoretical calculation, molecules without dominant
properties have been screened out and will not be compared in the next
step.
After completing the molecule
design, the calculatedE adsof all designed molecules on hydroxylated silicon dioxide surface
andG solv of designed molecules with different
branching degrees are adopted to screen the most suitable molecule for
rapid underwater adhesion and long-term antifouling. TheE ads is calculated by the most stable adsorption
structure from MD annealing simulation (Figure S1-12 ), and theG solv is acquired from DFT calculation. The
calculatedE adsof 12 molecules on the hydroxylated silica is listed in Table
S1 . The E ads of DOPA-PSBMA (Molecule 1),
DOPA-mPEG (Molecule 2) and DOPA-PDMAEMA (Molecule 3) are -26.35, -6.47,
-24.04 kcal/mol, respectively. We can find thatE ads (Molecule 1) >E ads (Molecule 2) >E ads (Molecule 3), indicating that Molecule 1 is
expected to be selected as the dominant monomer for subsequent molecular
design (Figure 2a ). The
adsorption energy in unit kcal/mol and J/g can express the adsorption
capacity and adsorption efficiency of the molecules, respectively. TheE ads of
Molecule 1, 4, 5 and 6 are -213.48,
-86.10, -239.32, and -197.50 J/g, respectively. It is indicated that the
adsorption efficiency of these molecules on hydroxylated silica surface
is in the order of E ads (Molecule 5)
> E ads (Molecule 6) >E ads (Molecule 1) >E ads(Molecule 4)
(Figure
2b ), which beyond our expectation. From the optimal adsorption
configurations of these molecules (Figure S1 , S4-6 ),
we found that the catechol groups of Molecule 1 and 5 are all
attached
to the substrate surface, however, those of Molecule 4 and Molecule 6
are only one in two and only three in four, respectively. It means that
whether the molecule is suitable for the target molecule depends on the
adsorption configuration rather than the degree of branching. The
difference in molecular adsorption configuration is the discrepancy inG solv. The calculatedG solv of Molecules 1, 4, 5, and 6 are -619.60,
-435.99, -502.79, and -407.36 J/g, respectively (Table S2 ). The
order of G solv is G solv(Molecule 1) > G solv (Molecule 5)
> G solv (Molecule 4) >G solv (Molecule 6). AsG solv increases, the hydrophilic part of the
molecule prefers to be in the stretched state in solution. Combining the
two effects of E ads andG solv, we found that tri-DOPA-PSBMA (Molecule 5)
with three branching degrees will be the most robust adhesive polymer
molecule of the four molecules. According to the reports of Li et al.50, the scaffolds connecting the head group and tail
chain are crucial for the configuration of the modified surface.
Molecules 5, 7, 8, and 9, all else being equal, have scaffolds of
varying degrees of flexibility. Molecule 7 has a rigid connecting
scaffold, whereas the scaffolds of Molecules 8 and 9 are soft with
longer chain lengths. TheE adsof Molecules 7, 8, and 9 are 151.2, -163.72, and -212.99 J/g,
respectively. Since Molecule 5 has the largestE ads, it continued to be selected as the dominant
target molecule. The possible reason is that the scaffold with too much
flexibility is not conducive to the molecular support on the substrate,
which results in a close distance between the hydrophilic group and the
silica substrate (Figure S8-9 ). In contrast, the rigid scaffold
will not ensure the simultaneous adsorption of multiple adsorption
groups on the substrate, which will reduce theE ads (Figure S7 ). TREN achieves a
balance between the flexibility and rigidity of molecules, thus it is a
suitable molecular scaffold for adhesion and antifouling. In addition to
the scaffold connection, the molecule’s headgroup also plays a
significant role in the adhesion process. TheE ads of Molecules 10, 11, and 12
are
-42.46, -14.80, and -165.77 J/g, respectively. From theE ads values of Molecules 10, 11, 12 and 5, it can
be inferred that the benzene ring does not contribute to the surface
adsorption, but hinders it. Although the E ads of
Molecule 12 with one phenolic hydroxyl group is much larger than that of
Molecules 10 and 11, it is still much smaller than that of Molecule 5
which has two phenolic hydroxyls. Hence, we found that the hydroxyl
groups bind firmly to the hydroxylated silica surface (Figs. 2 a
and b ). Based on these analyses of E ads andG solv on the surface of hydroxylated silica
substrate, Molecule 5 stands out since it owns the significant
advantages of adsorption and solvation properties and is chosen to be
the most suitable molecule for rapid underwater adhesion and long-term
antifouling.
The reason that four designed molecules (Molecules 1, 4, 5, and 6)
showed different properties in their E ads andG solv on the silica surface lies in their diverse
surface properties. The molecular polarity index
(MPI)51 was employed to analyze the hydrophilicity of
the designed molecules. The greater the polarity and the stronger
hydrophilicity of the molecule is, the larger the MPI of the molecule
is. The MPIs of the single head-single tail molecule (Molecule 1),
double head-double tail molecule (Molecule 4), triple head-triple tail
molecule (Molecule 5), and quadruple head-quadruple tail (Molecule 6)
are 34.73, 23.91, 32.27 and 26.72 kcal/mol, respectively. Molecule 5 has
the largest MPI, while molecule 4 has the smallest MPI, and the
difference between them was 10.82 kcal/mol.
Molecules
1 and 5 with MPI greater than 30 kcal/mol contain 1 and 3 sulfonate
groups exposed to water, respectively. The number of odd sulfonate
groups may result in a more stretched morphology of the molecule in
water, which causes a larger polar surface area of the molecule. While
the MPI of molecules 4 and 6 is less than 30 kcal/mol, the possible
reason is the even number of sulfonate groups cause the molecules to
curl up, resulting in a reduction in the polar surface area of the
molecules (Figure 2 and Table S3 ). The surfaces
modified with hydrophilic molecules will lead to the good antifouling
ability. Therefore, Molecule 5 is expected to be a favorite candidate
for antifouling surface modifier due to its properE ads and G solv and the
suitable hydrophilicity.
To further elucidate the superiority of Molecule 5 in modifying the
surface antifouling properties, the HOMO-LUMO and electrostatic
potential distribution (ESP) of molecules 1, 4, 5, and 6 were analyzed
(Figure 2 d-e ). The calculated HOMO-LUMO gaps of Molecules 1,
4, 5, and 6 were 5.677 eV, 5.646 eV, 5.344 eV, and 5.443 eV,
respectively. It is worth noting that Molecule 5 owns the smallest
HOMO-LUMO gap. The HOMO energy is -5.450 eV and the LUMO energy is
-0.106 eV, indicating that the
electron excitation energy of Molecule 5 is quite small, which will
enlarge the polarizability of Molecule 552. Due to the
high polarizability of Molecule 5, the electron in the molecule is
delocalized, which facilitates the modification of the hydrophilicity of
the silica surface. The ESP results reinforce our speculation. The head
group and scaffold are positively charged, whereas the hydrophilic group
sulfonate is negatively charged. Furthermore, as the electron
withdrawing ability of groups bound to the sulfur element increased, the
relative electrostatic potential absolute value decreased.
The
isoelectric point of silica is at a pH of 2.5, so silica surfaces
immersed in water are known to exhibit a negative charge
density53. The adsorption of target molecules on the
silica surface is mainly dominated by positively charged benzene ring
moieties adsorbed on the substrate, while negatively charged sulfonate
tail chains are far away from the substrate, which is consistent with
the structure we speculated. The negatively-charged sulfonate group
surrounded with highly hydrated layer will repel the protein
contaminants in the solution and play an antifouling effect. The surface
modified by Molecule 5 has a lot of negative electricity, which makes
its antifouling performance greatly improved (Figure 2e andTable S3 ). MD simulation was performed on the surface of silica
substrate modified by the target molecule with a polymerization degree
of 10. The designed molecules quickly adhered to the substrate surface
as shown from the snapshots and animation (Figure 3a andVideo 1 ). There was no structural damage to the silica surface
and modified molecules during MD simulation. Physical adsorption
occurred between DOPA with catechol groups and hydroxylated silicon
wafers, close to the silica surface, while PSBMA stretched away from the
silica surface, which could play an antifouling role. The thermodynamic
and kinetic stability of the silica surface modified by Molecule 5
during MD simulation indicates that the modification method is feasible.
It is consistent with all the above analysis results, demonstrating that
the designed molecules can be used for rapid underwater adhesion and
long-term antifouling resistance.