Competition-Driven Ligand Exchange for Functionalizing

Apr 5, 2019 - Zealand. b. The. MacDiarmid Institute for Advanced Materials and Nanotechnology, Department. of Chemistry, University of Otago,. P...
1 downloads 0 Views 2MB Size
Subscriber access provided by CAL STATE UNIV BAKERSFIELD

Article

Competition-driven ligand exchange for functionalizing nanoparticles and nanoparticle clusters without colloidal destabilization Dagmara Jaskólska, Dermot F. Brougham, Suzanne L. Warring, A James McQuillan, Jeremy Rooney, Keith C. Gordon, and Carla J Meledandri ACS Appl. Nano Mater., Just Accepted Manuscript • DOI: 10.1021/acsanm.9b00183 • Publication Date (Web): 05 Apr 2019 Downloaded from http://pubs.acs.org on April 12, 2019

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 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 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.

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 57 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

ACS Applied Nano Materials

Competition-driven ligand exchange for functionalizing nanoparticles and nanoparticle clusters without colloidal destabilization Dagmara E. Jaskólska,a,b Dermot F. Brougham,c Suzanne L. Warring,a A. James McQuillan,a Jeremy S. Rooney,a,b Keith C. Gordon,a,b Carla J. Meledandria,b*

aDepartment

of Chemistry, P.O. Box 56, University of Otago, Dunedin 9054, New

Zealand; bThe MacDiarmid Institute for Advanced Materials and Nanotechnology,

Department of Chemistry, P.O. Box 56, University of Otago, Dunedin 9054, New Zealand; cSchool of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.

Keywords: Ligand exchange, surface functionalization, nanostructures, infrared

spectroscopy, interfacial interactions

ABSTRACT

ACS Paragon Plus Environment

1

ACS Applied Nano Materials 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 57

We present a novel and scalable approach to tailored ligand exchange in stable

suspensions of nanoparticles and nanoparticle clusters which is applicable to a wide

range of nanoparticle types. Competition-Driven Ligand Exchange (CDLE) uses a

substrate with higher affinity for the primary ligand to “activate” the dispersed

nanoparticles for functionalization with a secondary ligand (which itself is not subject to

substrate competition and which cannot exchange in the absence of the substrate). This

approach allows ligand replacement without destabilization of the colloid. Ligand

exchange while maintaining colloidal stability and hydrodynamic particle size is

demonstrated for iron oxide nanoparticles and nanoparticle clusters in suspension, and

a range of ligand types is used to impart new functionality, demonstrating the general

applicability of the approach. Time-dependent attenuated total reflectance-infrared

spectroscopy is used to investigate the nature and dynamics of the critical interfacial

interactions that take place within the colloidal system and govern the CDLE process.

Novel CDLE reactors applicable to suspensions of dispersed nanoparticles and

monodisperse nanoparticle assemblies are described.

ACS Paragon Plus Environment

2

Page 3 of 57 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

ACS Applied Nano Materials

INTRODUCTION

Control of nanoparticle (NP) surface characteristics (e.g. charge, solvophilicity,

conductivity, reactivity) is essential for optimizing the properties and behavior of

functional nanomaterials, thereby expanding their versatility and efficacy for a broad range of applications.1-3 A common strategy to tune the surface chemistry of NPs is to

passivate their surface with functional molecules, or ligands, which govern NP

interactions with the surrounding environment.

Surface ligands are typically introduced during NP synthesis as they play a critical role in controlling nanocrystal size, composition, morphology and dispersibility;4-5 however,

the range of ligands best suited for a given synthesis is not necessarily compatible with

the desired application, which may require, for example, the use of stimuli-responsive molecules or those that facilitate larger scale nanoparticle assembly.6-7 Enormous

research efforts have thus been directed toward the development of post-synthetic

surface modification techniques in order to introduce various functional groups, leading

ACS Paragon Plus Environment

3

ACS Applied Nano Materials 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 4 of 57

to the production of NPs with desired properties and extending their potential application

range. As a result, there are numerous reported strategies, which vary significantly in

terms of their complexity, selectivity and general applicability.

Non-covalent means of manipulating the surface-bound monolayer have been explored,

for instance, though encapsulation strategies whereby a secondary layer composed of

amphiphilic molecules is formed around the monolayer-coated NPs, driven by hydrophobic interactions with the NP-bound ligands,8 or through host-guest

complexation between surface-bound surfactant molecules and supramolecular macrocycles, aided by ongoing advances in supramolecular design.9-11 While these

strategies are useful for colloidal NP phase transfer and to achieve NP dispersity in

alternative solvents, such encapsulation methods can appreciably increase the

solvodynamic diameter of the particles. This is unfavorable for many applications,

particularly biomedical applications, and achieving sufficient selectivity of the outermost

ligand layer remains a challenge.

ACS Paragon Plus Environment

4

Page 5 of 57 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

ACS Applied Nano Materials

An alternative strategy involves direct covalent modification of the surface-bound

monolayer with a view to precisely controlling the molecular structure, and therefore functionality, of the ligand shell.12 This approach, however, requires reactive ligands,

which can be difficult to achieve from synthesis alone, and therefore typically demands

one or more ligand exchange reactions to be carried out to displace the surface-bound layer prior to covalent modification.13-17 As a result, only a few examples of covalent

modification of as-synthesized monolayer-stabilized NPs can be found in the literature, and amongst these examples, NP aggregation is commonly noted.12

Ligand exchange reactions as a standalone, post-synthetic surface modification method

to directly tune NP surface chemistry have been actively investigated as they can

overcome some of these limitations. The potential to increase the size of the

nanostructure and screen the core material is reduced compared to encapsulation

techniques, reactive ligands are not required, and in many cases, NP aggregation can

be prevented, or at least minimized.

ACS Paragon Plus Environment

5

ACS Applied Nano Materials 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 6 of 57

Most ligand exchange reactions utilize an excess of free ligand in solution resulting in the eventual replacement of the original surface-bound ligands.18-20 To be successful

with this approach, the incoming ligand should have a higher headgroup affinity for the

NP surface than the original ligand, which limits the range of ligands that can be

employed for these reactions, and the efficiency of exchange is affected by solvent

polarity as well as the properties and relative abundance of incoming/outgoing ligands.

As a result, a great variety of viable system-specific ligand exchange processes have been developed,21-24 and while some of these can be adapted, the need for generally

applicable methods still remains. This is perhaps not surprising considering the

significant variation possible in the thermodynamics of the (incoming vs. outgoing)

ligand/NP interaction, surface dynamics and rates of desorption, ligand-solvent polarity,

the faceted nature of NPs with different sizes/shapes, as well as the slow surface

reconstruction that can take place over time in some NP systems which can affect the reactivity of surface-bound ligands.19

ACS Paragon Plus Environment

6

Page 7 of 57 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

ACS Applied Nano Materials

Some of these challenges are addressed in the work presented through the use of a

substrate that serves to initiate desorption of the surface-bound ligands of the dispersed

NPs (Figure 1(a)), while concurrently acting as a sink for these outgoing ligands (Figure

1(b)), thereby removing them from solution. This reduces competition between incoming

and outgoing ligands and creates vacant sites on the NP surfaces, which are available

for the incoming ligands (Figure 1(c)). Effectively, the ligand desorption feature of the

‘competitive stabilizer desorption’ (CSD) procedure first introduced by Stolarczyk and co-workers for controlled assembly of magnetic iron oxide nanoparticles (IONPs),25 is

the first step in a new ligand exchange procedure. In their 2009 paper, Stolarczyk et al.25 reported the assembly of IONP clusters from oleic acid (OA)-stabilized particles in

heptane when the suspension was placed over cyanopropyl-modified silica (CN-silica),

as a result of OA depletion by silica. CSD was subsequently shown to be useful for preparing TiO2, or metal ferrite assemblies,26 two-component (magnetic-noble metal) co-assemblies27 and also for controlling emergent magnetic properties through NP size;28 however, the silica surface/OA/IONP/solvent interactions, critical to the process,

were not addressed. The potential use of magnetic iron oxide NPs that are stabilized in

ACS Paragon Plus Environment

7

ACS Applied Nano Materials 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

ACS Paragon Plus Environment

Page 8 of 57

Page 9 of 57 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

ACS Applied Nano Materials

substrate (b), and adsorption of the incoming ligand at the newly-created vacant sites at

the NP surface (c), all while maintaining particle dispersity.

Here we describe for the first time the use of a competing substrate that can

continuously activate the NP surface by gradual irreversible desorption of the primary

ligand, enabling controlled ligand exchange; the process is referred to as ‘competition

driven ligand exchange’, or CDLE. The new approach is shown to prevent particle

aggregation, preserve particle size and monodispersity, and enable particle dispersion

in more polar solvents. The key interfacial interactions underpinning

competition/depletion processes are investigated through attenuated total reflectance

infrared (ATR-IR) spectroscopy, and the ability to convert between the two possible

outcomes, exchange and assembly, is demonstrated. The utility of the approach for

exchanging different ligand types onto the surface of both IONP clusters of a desired

size and onto dispersed NPs in suspension while maintaining the colloidal state

ACS Paragon Plus Environment

9

ACS Applied Nano Materials 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 10 of 57

(unchanged size and monodispersity) is shown. The design and validation of reactors

suitable for scaling up CDLE for each of these applications is also described.

EXPERIMENTAL SECTION

Materials

Oleic acid (OA, standard laboratory grade) was purchased from ECP Laboratory &

Research Chemicals. Oleylamine (OAm, 70%, technical grade), 1,2-hexadecanediol

(HDD), phenyl ether (99.0%) were obtained from Sigma-Aldrich. Iron (III)

acetylacetonate (99%) was purchased from Merck (NJ, USA). Heptane (99.0%) was

purchased from VWR International S.A.S. Tetrahydrofuran (THF, standard laboratory

grade), ammonia solution (35%, standard laboratory grade) and hydrogen peroxide

(30%, standard laboratory grade) were purchased from Thermo Fisher Scientific.

Unmodified silica gel P60 (silica gel) with 40-63 O

particles was purchased from

Silicycle. The TLC plates used in this work, purchased from Merck, had a 0.20 mm

ACS Paragon Plus Environment

10

Page 11 of 57 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

ACS Applied Nano Materials

absorbent layer composed of silica gel with 13% gypsum used as a binder. The silica

particles had a 6 nm pore size and diameter of 5-17 O

and the gel layer was absorbed

on a 200 x 200 mm aluminum sheet with manganese-activated zinc silicate as a UV254

fluorescent indicator. No thermal activation was applied to any of the listed silica

sources. All chemicals were used as received.

Methods

Infrared Spectroscopy. Infrared spectra were collected with Fourier transform infrared

spectrometers mostly by attenuated total reflection (ATR). Spectra are mainly presented

as absorbance spectra which are effectively difference spectra between sample and

background spectra.

Time-dependent ATR-IR spectra during ligand adsorption/desorption experiments were

carried out with a silicon prism and heptane solutions. Spectra were collected at room

temperature with a Digilab FTS4000 FTIR spectrometer having a Peltier cooled DTGS detector and globar source. Spectra were collected at 4 cm-1 resolution with spectral

analysis performed using Digilab Win IR Pro v.4.0 software and further processed with

ACS Paragon Plus Environment

11

ACS Applied Nano Materials 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 57

OriginPro, v.8.5 (OriginLab Corporation). Background spectra were from heptane on the

silicon prism resulting in heptane absorptions being largely cancelled. Heptane solution

spectra obtained from the silicon prism used pure heptane as background.

Infrared spectra of free ligand and surface-functionalized IONPs were acquired in

transmission mode using a Bruker Vertex 70 spectrometer (BRUKER OPTIK GmbH,

Ettlingen) with a room temperature DLaTGS detector by co-addition of 128 scans with a spectral resolution of 4 cm-1 and an 8 mm aperture. Approximately 1 mL of a sample

was placed onto a NaCl window (25 mm diameter) and dried under vacuum which was

then covered with a second window. Background spectra were acquired with two clean

NaCl windows. Spectra were initially processed using GRAMS AI 9.1 (Thermo Fisher

Scientific Inc.) in which a multi-point linear baseline correction was applied before

performing a normalization process using OriginPro, v.8.5.

Ligand adsorption/desorption experiments. Infrared spectra were collected with a 45°

bevel 50 x 20 x 2 mm trapezoidal silicon prism mounted in a stainless-steel cell. Before

each experiment, the prism was cleaned using the RCA-1 method. In this procedure,

ACS Paragon Plus Environment

12

Page 13 of 57 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

ACS Applied Nano Materials

the prism was immersed in a 25% solution of NH4OH, heated to 70 °C, followed by the addition of 30% H2O2 and left for 15 min.32 The prism was then washed with copious amounts of water, dried under N2, then remounted. The spectral region below 1500 cm-1 was not viable for IR analysis due to spectral distortion by silicon absorption below ~1450 cm-1, and total absorption below ~1200 cm-1. The prism was first equilibrated with

30 mL of heptane, which was recirculated over the prism using a laminar flow of 3.1 mL min-1 (flow rate not critical to the experiment) with Viton® tubing. A certain volume of OA

(or OAm) stock solution was then added to achieve a solution concentration of 1 mM. In

the case of the adsorption/desorption study of OA, once adsorption equilibrium was

established, a clean heptane solution was flowed over the prism and desorption was

subsequently monitored spectroscopically. The initial 5 min of the experiment were

recorded using 8 co-added scans to give a temporal resolution of 10 s; the remainder

was performed using 64 co-added scans, 75 s for each spectrum. The ATR-IR study

was performed at room temperature. ATR-IR solution spectra of OA, and OAm, in

heptane placed on a silicon prism were also recorded according to the procedure

described in this section.

ACS Paragon Plus Environment

13

ACS Applied Nano Materials 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 57

Synthesis of IONPs. Heptane suspensions of IONPs stabilized with OA were synthesized according to a previously published method.33 The iron concentration of

each sample was determined by inductively coupled plasma-mass spectrometry (ICP-

MS), which was performed on an Agilent 7500ce instrument (Agilent Technologies;

USA). Samples were prepared for analysis by drying a known volume of the suspension

in a Teflon® vessel followed by digestion using 1:3 HCl:HNO3.

Synthesis of 2-azido-2-methyl-propionic acid 2-phosphonooxy-hexyl ester (C6). 2-azido-

2-methyl-propionic acid 2-phosphonooxy-hexyl ester was synthesized as described in

detail in the Supporting Information (SI).

Cluster assembly experiments. Cluster assembly experiments in a cuvette. Cluster

assembly experiments performed in a quartz cuvette were set up as described previously.25, 33 Briefly, 50-52 mg of silica gel were placed on the bottom of the cuvette,

then wetted with a few drops of the appropriate solvent. Next, 1.2 mL of the IONP

suspension at a known iron concentration were carefully placed over the silica layer.

The assembly of IONP clusters was then continuously monitored using dynamic light

ACS Paragon Plus Environment

14

Page 15 of 57 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

ACS Applied Nano Materials

scattering (DLS; Zetasizer Nano ZS, Malvern Instruments Ltd) by measuring the hydrodynamic diameter (dH, nm), polydispersity index (PDI) and derived count rate (DCR, kcps) over the course of many hours.

Cluster assembly experiments in a TLC plate apparatus. Using the TLC apparatus (Figure 2 (c) and (d)), cluster assembly experiments were performed by placing a

heptane suspension of IONPs ([Fe] = 3.0 mM) in the glass vessel, to which 4 TLC

places were introduced via the threaded Teflon® holder. This apparatus was connected

to the Zetasizer Nano ZS instrument through the auto-titrator accessory (Malvern

Instruments Ltd). Using heptane-resistant tubing, the NP suspension was recirculated

to/from the DLS, and size measurements were performed over time in a flow-through

cell (Hellma GmbH & Co, Type No. 176.751.QS, light path 3x3 mm). The NP cluster

suspension was removed from the glass vessel and retained for characterization.

ACS Paragon Plus Environment

15

ACS Applied Nano Materials 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

(a)

(b)

(c)

Page 16 of 57

(d)

Figure 2. (a) Schematic diagram of the components of the Teflon® cell, developed in-

house, to enable CDLE. The cell is composed of 3 Teflon® rings (o.d. = 80 mm, i.d. =

50 mm), 2 PDMS membranes (65 mm diameter) and 12 screws. The middle ring also

possesses 2 gaskets and 2 inlets which are closed with stoppers on both sides to allow

access to the chamber between the two PDMS membranes. The cell can hold up to 20

g of silica gel within the chamber; (b) photograph of the entire ligand exchange

apparatus containing the fully-assembled Teflon® cell, immersed in an IONP

suspension, within a glass holder placed on a magnetic stir plate. Solvent-resistant

tubing enables transport of the suspension to/from a measurement cell placed within the

DLS instrument; (c) photograph of the components of the apparatus consisting of two

ACS Paragon Plus Environment

16

Page 17 of 57 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

ACS Applied Nano Materials

TLC plates (430 mm2 of silica gel per plate), a threaded Teflon holder and a glass

vessel; (d) the same apparatus assembled together and containing a NP suspension,

connected to the auto-titrator and DLS instrument.

Ligand exchange experiments. Ligand exchange experiments on IONP clusters using

OAm. CSD-based cluster assembly was performed on a heptane suspension of OAstabilized IONPs placed over unmodified silica in a quartz cuvette as described above,

and the assembly was monitored continuously with DLS (Figure S1, SI). An OAm

solution (~10 mg in 100 O of n-heptane) was added to the suspension after 4 h, when the clusters reached dH of ~65 nm (indicated by the orange arrow in Figure S1).

Ligand exchange on dispersed IONPs using OAm. Using the Teflon® cell apparatus specifically developed for CSD-ligand exchange (Figure 2 (a) and (b)), the apparatus

was assembled with ~20 g of solid, unmodified silica housed between two SolSep®

poly-dimethyl siloxane (PDMS) membranes (MWCO between 300-750) cut to the

required size from the supplied A4 sheets. The Teflon® cell was placed within a glass

ACS Paragon Plus Environment

17

ACS Applied Nano Materials 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 57

vessel, to which up to 160 mL of the IONP suspension at a known iron concentration

was added. The Teflon® cell was connected to the Zetasizer Nano ZS and auto-titrator

accessory using heptane-resistant tubing. Recirculation and automation features

allowed size measurements to be performed over 16 h using the flow-through cell in the

DLS instrument as small >O ? volumes of an OAm solution in heptane were added to the

suspension of OA-stabilized IONPs using the auto-titrator. The IONP suspension post

ligand exchange was removed from the glass vessel and retained for characterization.

Ligand exchange on dispersed IONPs using 2-azido-2-methyl-propionic acid 2phosphonooxy-hexyl ester (C6). Using the TLC plate apparatus (Figure 2 (c) and (d)), ligand exchange experiments were performed by placing 16 mL of heptane:THF (1:1)

suspension of IONPs ([Fe] = 6.0 mM) in the glass vessel, to which 4 TLC places were

introduced via the threaded Teflon® holder. The apparatus was attached to the

Zetasizer Nano ZS instrument through the auto-titrator accessory and size

measurements were periodically performed using DLS after recirculating the

suspension through the flow-through cell using Viton® tubing. The IONP suspension

ACS Paragon Plus Environment

18

Page 19 of 57 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

ACS Applied Nano Materials

post ligand exchange was removed from the glass vessel and retained for

characterization.

RESULTS AND DISCUSSION

The following four sections have been structured in a progressive manner, advancing

from a discussion of key results obtained from fundamental spectroscopic studies of

critical interfacial interactions to the presentation of a new approach to ligand exchange

on the surface of dispersed NPs and NP clusters.

1. IR spectroscopy during ligand adsorption on a SiO2 surface

Time-dependent ATR-IR spectroscopy measurements used the experimental set-up

depicted in Figure 3(a) to investigate the adsorption and desorption of OA and OAm

to/from a silicon prism from heptane solvent. It has been shown previously that a silicon

prism surface oxidizes under ambient conditions to form a ~2 nm SiO2 layer, making the prism surface an appropriate model for SiO2 surfaces,32 such as those used in

ACS Paragon Plus Environment

19

ACS Applied Nano Materials

CSD/CDLE experiments. These measurements were performed to gain insight into the

mechanism for competitive depletion of free OA from the heptane suspension of IONPs

in the presence of silica gel, and with a view to identifying the characteristics of viable

substrates for future adaptation and advancement of CSD/CDLE.

desorption of oleic acid with heptane oleic acid still remains at prism

Absorbance

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 57

adsorption of oleic acid onto silica

(a)

2000

Wavenumber

(b)

Figure 3. (a) Schematic of the apparatus used for time-dependent ATR-IR

measurements as described in the Experimental section; (b) Temporal variation of integrated absorbance of the 1712 cm-1 carbonyl peak during adsorption of OA from 0.3

mM heptane solution to silica and desorption into heptane (Inset: selected spectra

showing temporal variation of C=O modes of adsorbed OA during adsorption from 0.3

mM heptane solution); background spectra provided by pure heptane.

ACS Paragon Plus Environment

20

Page 21 of 57 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

ACS Applied Nano Materials

Significant features of the IR spectra of OA adsorbed to the oxidized surface of the

silicon prism from 0.3 mM OA solution in heptane are shown as an inset in Figure 3(b).

Comparison of these data to an IR solution spectrum of 0.1 M OA in heptane (Figure S3, SI) shows that the absorption peak at 1712 cm-1, assigned to stretching of the C=O bond >V>%U,?? of the OA based on previous assignments from the literature,34 is shifted from 1714 cm-1 on adsorption to silica, implicating hydrogen-bonding of the C=O to surficial silanols.35 With the apparatus used for ATR-IR measurements, there is no

significant contribution to this absorption from solution OA.

The absorbance of the V>%U,? peak with respect to time is plotted in Figure 3(b), with

the absorbance increase implying that OA is adsorbing onto SiO2. A rapid increase was initially observed within the first 5 min of the experiment; however, a further gradual

increase in absorbance of ~0.0005 was noted in the following ~2.5 hours, followed by a

rapid absorbance decrease to a plateau during the desorption phase when the flow was

switched to pure heptane. This behavior corresponds to some of the OA being strongly

ACS Paragon Plus Environment

21

ACS Applied Nano Materials 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 22 of 57

adsorbed and some weakly adsorbed. The corresponding data for adsorption from 1

mM OA solution is shown in Figure S4, with the rapid initial rise in absorbance reaching

a higher plateau, but a similar absorbance plateau being observed in the desorption

phase. Thus, the higher OA concentration resulted in more OA adsorption in the form of

the weakly adsorbed component.

Regardless of the initial OA concentration, when pure heptane was flowed over the prism, a fast initial decrease in absorbance of the 1712 cm-1 absorption band was

observed, reaching a plateau at a value of 0.0015 in both cases (see Figures 2(b) and

S4). This clearly indicates that a significant amount of OA is still adsorbed quite strongly

to the prism surface, probably through cyclic double hydrogen bonds (shown

schematically in Figure S5, SI), which has previously been shown to be a very strong mode of adsorption.34-36 The OA more easily displaced by the pure heptane (indicated

by rapid desorption) is likely loosely bound OA adsorbing to the silica surface through a

weaker interaction, such as monomeric hydrogen bonds (Figure S5), or a weakly bound

secondary layer with the strongly adsorbed OA reaching monolayer surface coverage.

ACS Paragon Plus Environment

22

Page 23 of 57 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

ACS Applied Nano Materials

This IR data is in good agreement with observations and results acquired from CSD

cluster assembly experiments, both in terms of the present work, and previously reported studies.25-26

The ATR-IR adsorption study was repeated for 1 mM OAm in heptane, and the results

are shown in Figure S6, SI. Notably, the spectra lack a temporal increase in absorbance in the 1620 cm-1 range which is associated with the N-H bending mode of OAm37-38 (a

solution spectrum of 0.1 M OAm is shown in Figure S3, SI for comparison). If adsorption of OAm to silica were to occur, an absorbance increase around 1620 cm-1 should be observed, though this absorption is weaker than that of the 1712 cm-1 absorption of OA

making detection of adsorbed OAm somewhat more difficult. A loss in absorbance of the bands associated with CH2 stretching modes (2970 – 2880 cm-1) can be observed over time in the ATR-IR spectra, which can be correlated with the displacement of

heptane at the prism surface. Hence, OAm does not appear to adsorb significantly to

the silica surface from heptane solution, or if it does, the interaction is much weaker

ACS Paragon Plus Environment

23

ACS Applied Nano Materials 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 24 of 57

than that observed for OA, indicating that an amine group will not compete with a

carboxylic acid group for adsorption to the surface of silica from heptane solution.

Thus, for viable competition driven exchange, the secondary ligand should be selected

to have reduced attraction to the substrate. So in this case, with silica as the substrate,

it should not possess a carboxylic acid group, but could possess an amine group, or

another functional group unlikely to undergo hydrogen bonding with the hydroxyl groups

on the silica surface.

2. Cluster assembly by competitive stabilizer desorption (CSD): Solvent/silica interfacial

interactions

While the interaction between OA and silanol groups on the silica surface is relevant for

the CSD process, there are many interfacial interactions within the IONP

suspension/silica system; understanding the interactions between the silica surface and

the solvent molecules in particular may be important for all competition-related colloidal

phenomena.

ACS Paragon Plus Environment

24

Page 25 of 57 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

ACS Applied Nano Materials

Hydrophilic silica gel contains an abundance of single, isolated, geminal and vicinal hydroxyl (silanol, SiOH) groups distributed on the surface.39 When it is immersed in a

nonpolar solvent containing a solute, such as OA, the solute can disrupt the interfacial

solvent layer (as only weak intermolecular forces are present) and interact directly with

silanol groups. In a polar solvent, however, the solvent molecules cannot easily be

replaced at the silanol surface by most solutes due to relatively strong solvent bonding,

which can include hydrogen bonding. The solute molecules instead interact with the

solvent layer rather than depleting it. If, however, the interaction between the solute and

silica surface are sufficiently strong, the solute can displace the interfacial solvent molecules.40-41 This has direct implications for understanding and optimizing

competition/depletion processes, and for expanding CSD assembly/CDLE processes to

a wider range of solvents, including polar solvents.

The role of the solvent was studied by performing CSD assembly experiments under a

range of solvent conditions. A series of experiments were performed in which OAstabilized IONPs prepared by a thermal decomposition method42 were dispersed at

ACS Paragon Plus Environment

25

ACS Applied Nano Materials 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 26 of 57

approximately the same concentration in solvents including chloroform, heptane, THF and a 1:1 mixture of heptane and THF, and placed over silica in a standard cuvette. dH and DCR were monitored over time by DLS, and the results are presented in Figure 4.

dH and DCR were found to increase more rapidly for the experiment performed in heptane with the DCR values reaching a maximum within 4-5 h. Conversely, there was almost no change in dH or DCR recorded over 18 h for the experiment carried out in THF. When a 1:1 solvent mixture of heptane and THF was used, the rate of increase of

dH and DCR was intermediate between those observed for the experiments performed in the respective pure solvent. In the case of chloroform used as a solvent, both dH and DCR increased at a slower rate than when the IONPs were dispersed in heptane. Note that in all cases, in the absence of the silica substrate, both dH and DCR were stable and unchanging over many hours.

ACS Paragon Plus Environment

26

Page 27 of 57 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

ACS Applied Nano Materials

ACS Paragon Plus Environment

ACS Applied Nano Materials 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 28 of 57

polarity than heptane. Unlike heptane, the polar solvents will compete with OA for

binding sites at the silica surface.

A schematic representation of the interactions between THF and chloroform molecules

and the surface of silica is shown in Figure 5. THF contains an oxygen atom, which is

an electron-donor and can hydrogen bond to the silanol groups of silica, thereby

blocking the access for OA. While chloroform molecules cannot form hydrogen bonds to

the silica surface, they can participate in weaker dipole-dipole interactions with the

hydroxyl groups of silica.

Dipole-dipole interaction between CHCl3 and hydroxyl group at silica surface Hydrogen bond between THF and hydroxyl group at silica surface

-

O

Cl

-

Cl

Cl +

H

H

O

O

O O

-

Si

Si O

H H

O

+

Si O

O O

O

Figure 5. An illustration of interactions between two solvents, THF and chloroform, and

the hydroxyl groups of silica.

ACS Paragon Plus Environment

28

Page 29 of 57 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

ACS Applied Nano Materials

3. Competition driven ligand exchange (CDLE) using OAm

By applying the knowledge gained from ATR-IR we have adapted competition/depletion

as an approach to ligand exchange. For initial proof-of-concept experiments, OAm was

selected as the secondary ligand as it does not contain a carboxylic acid functional

group, but has similar solubility to OA and can provide sufficient steric stabilization in heptane to prevent particle aggregation.43 We first performed ligand exchange, by

adding the secondary ligand, to a suspension of small IONP clusters during the CSD

process (see Figure S1), as in this case a sub-population of surface depleted species

are demonstrably present. Following the addition of OAm, there was a brief period of

fluctuation in the DLS response after which the cluster size stabilized at dH ~48 nm. This was interpreted as successful partial ligand exchange (following an extended period of

partial depletion associated with cluster assembly).

An equivalent procedure was then developed for fully dispersed IONPs in heptane,

again using OAm as the secondary ligand. A new apparatus was designed and

ACS Paragon Plus Environment

29

ACS Applied Nano Materials 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 30 of 57

fabricated (Figure 2(a) and (b)) for ligand exchange which enabled significant scale-up

and easy removal of the final IONP suspension from contact with the substrate, due to

physical separation of the substrate using a semi-permeable membrane. Briefly, the

apparatus consisted of a Teflon cell that could house the silica phase between 2

solvent-resistant, semi-permeable membranes. The Teflon cell was immersed in an

IONP suspension contained within a glass holder with specially-designed access points.

The apparatus was connected to the DLS instrument as described in the experimental

section. The lack of direct contact between the IONPs and the substrate provided by the

semi-permeable membrane demonstrates depletion of the IONP ligands is via the continuously-generated free ligand fraction, i.e. OA molecules diffuse through the

dialysis membrane to reach and irreversibly bind to the silica surface (see Figure S7).

Two experiments were performed using this apparatus; in one case, no secondary

ligand was added to the IONP suspension, and dH was observed to increase over time as expected (Figure 6(a), blue squares), demonstrating CSD assembly and confirming

the performance of the apparatus (allowing optimization of the silica surface exposed).

ACS Paragon Plus Environment

30

Page 31 of 57

In the second case, OAm was titrated drop-wise (~1.3 x 10-6 mol min-1; OAm/Fe molar equivalents: 4.6 x 10-3 to 4.3 over 15.3 h; 0.02 to 16 times excess ligand with respect to

total IONP surface area) into a suspension of OA-stabilized IONPs (at the same NP concentration) placed over silica. In this case CSD did not occur; dH < 20 nm for 65+ hours, see Figure 6(a), orange circles. It is proposed that during this experiment, as

oleate molecules were depleted from the surface of NPs and attracted to the surface of

silica gel, OAm molecules, which have minimal affinity for the substrate, filled the empty

sites around the NPs at a rate sufficient to maintain stability. After ~16 h, the resulting

IONP suspension was removed from the apparatus and was found by DLS to be stable,

with dH < 20 nm after ~67 h.

DCR / PDI kcps

dH / nm

80

350

700 0.6

dH / nm PDI DCR / kcps

300 60

dH / nm

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

ACS Applied Nano Materials

600

250

0.4 500

200

40

150

400

100

20

300

50 0 0

(a)

10

20

30

40

Time / h

50

60

70

0.2

0

200 0.0 0

20

40

(b)

60

80

100

Time / h

ACS Paragon Plus Environment

31

ACS Applied Nano Materials 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 32 of 57

Figure 6. (a) dH recorded as a function of time using DLS for cluster growth of spherical IONPs in heptane suspension (blue squares) and for the analogous experiment but with

in situ OAm addition (orange circles), with both experiments carried out using the home-

built Teflon cell CSD apparatus (Figure 2(a) and (b)); (b) DLS results for the ligand

exchange procedure performed on the surface of individual IONPs suspended in a 1:1

mixture of heptane and THF, carried out in the TLC plate CSD apparatus.

The CDLE approach is shown schematically for IONP clusters and for dispersed IONPs

in Figure 7(b) and (c), respectively; CSD is represented in Figure 7(a) for comparison.

As with CSD, the CDLE process begins as free OA molecules present in suspension

are attracted to the surface of silica where they undergo strong hydrogen bonding with

silanol groups, depleting them from the continuous phase. At the same time, a

secondary ligand, which does not possess a carboxylic acid group and therefore does

not undergo the same strong interactions with the silanol groups, is made available in

suspension (to small clusters (b) or individual particles (c)). Next, due to a shift in the

ACS Paragon Plus Environment

32

Page 33 of 57 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

ACS Applied Nano Materials

equilibrium between bound and free OA, IONP surface-bound oleate is desorbed in an

attempt to re-establish the equilibrium. This free OA is also attracted to the silica

surface, where it binds irreversibly. At the same time, it is proposed that the secondary

ligand fills the depletion sites on the IONPs, maintaining the dispersity of the NPs and/or

clusters, or allowing for their re-dispersion in other solvents, depending on the nature of

the secondary ligand. Critically, the approach preserves full particle/cluster dispersion,

is suitable for further scale-up, and in principle, it can be applied to a variety of magnetic

and non-magnetic NP types.

ACS Paragon Plus Environment

33

ACS Applied Nano Materials 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 34 of 57

Figure 7. A schematic representation of (a) CSD assembly of IONP clusters from OAstabilized particles in heptane,27 (b) CDLE performed on the surface of IONP clusters,

and (c) CDLE performed on dispersed IONPs in suspension. In all cases, the presence

of a silica gel-covered TLC plate (in a vertical orientation) is represented by grey

ACS Paragon Plus Environment

34

Page 35 of 57 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

ACS Applied Nano Materials

spheres; OA molecules are represented in blue, and a secondary ligand in red. Brown

spheres symbolize IONPs.

ATR-IR spectroscopy was used to characterize the IONPs following the experiments

performed with OAm (Figure 8). The spectrum does not contain any bands

characteristic for OA molecules (Figure S3), which indicates the successful depletion of

free OA from suspension by silica, a requirement for subsequent desorption of surfacebound oleate. Moreover, there were no bands around ~1529 cm-1 or ~1430 cm-1, known

to arise from asymmetric and symmetric stretching of surface-bound carboxylate groups.44 After CDLE the IONP spectrum shows an obvious absence of a band ~1620 cm-1 which is characteristic of the bending vibration >\>5J2)) of free OAm in solution.34 Instead, a band appears at 1578 cm-1, which is assigned to the NH2 scissoring vibration of OAm.38, 45 This analysis confirms exchange of OA with OAm at the nanoparticle

surface to give OAm-IONP suspensions by CDLE. While this IR analysis alone cannot

definitively confirm the absence of any residual bound oleate, particularly given the

ACS Paragon Plus Environment

35

ACS Applied Nano Materials

challenges that exist in resolving OA/OAm bands when both surfactants are present,46 it

is clear that the vast majority of the surface ligands have been exchanged with OAm.

The analysis confirms that it is possible to switch the outcome of competition/depletion

from assembly (CSD) to exchange (CDLE) by introducing a secondary ligand.

0.15

Absorbance

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 36 of 57

as CH2 stretch 2922

0.10 as CH3 stretch 2956

s CH2 stretch 2853

NH2 scissor 1578 CH3 bend 1465

0.05

sym CH3 rock 1377

0.00 3600

3200

2800

2400

2000

1600

1200

800

Wavenumber / cm-1

Figure 8. ATR-IR spectra recorded for IONPs post-CDLE with OAm.

4. Competition driven ligand exchange (CDLE) using functional ligands

ACS Paragon Plus Environment

36

Page 37 of 57 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

ACS Applied Nano Materials

To demonstrate the general applicability of CDLE, 2-azido-2-methyl-propionic acid 2-

phosphonooxy-hexyl ester (C6) was used as the secondary ligand in the place of OAm. C6 was synthesized by a modification of published procedures;47-48 the molecule

possesses a phosphonic acid group, known to bind strongly to the surface of metal oxides, thereby stabilizing them in suspension.49-50 The azide group on the other end of

the molecule offers a characteristic IR signature, enabling straightforward

characterization of C6-IONPs, and the possibility of further chemical modification

through ‘click chemistry’. Moreover, C6 is soluble in THF, enabling delivery to OA-

IONPs suspended in a 1:1 volume ratio of heptane:THF.

For CDLE using the C6 ligand, a new apparatus was developed (Figure 2(c) and (d)),

with a view to increasing the rate of competition/depletion, as compared to the previous device, for which the PDMS membrane was determined to be rate limiting.51 The

second apparatus did not include a membrane and the source of silica was changed

from loose solid powder to silica-coated TLC plates (Figure 2), which could be

removed/replaced at any time, enabling precise control over the substrate exposure

ACS Paragon Plus Environment

37

ACS Applied Nano Materials 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 38 of 57

(surface area and time). The TLC plates (up to 8 can be used at one time) were fixed

vertically from the top of a 16 mL glass vessel using a Teflon® holder, which could also

be used to connect the entire apparatus to the auto-titrator/DLS.

To confirm that this new apparatus could be successfully used for competition/depletion

experiments, CSD was first performed using OA-IONPs in heptane, as described in the

experimental section. The results are shown in Figure S2, confirming successful cluster

assembly. The rate of CSD could also be effectively adjusted by changing the number

of TLC plates used in the apparatus (Figure S8). The new apparatus was then used to

perform CDLE on dispersed OA-IONPs in 1:1 heptane:THF using C6 as the secondary

ligand (C6/Fe molar equivalents = 1.4, with the C6 aliquot added in full at the start of the

experiment); the DLS results are shown in Figure 6(b). As before, due to the presence

of the secondary ligand, dH (blue solid squares) remained unchanged at < 15 nm for 100 h. DCR and PDI (open squares and purple circles, respectively) decreased only

very slightly over the entire course of the experiment, suggesting a very small loss of

NPs through sedimentation. It is proposed that during this experiment oleate molecules

ACS Paragon Plus Environment

38

Page 39 of 57 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

ACS Applied Nano Materials

were exchanged for C6 ligands, yielding fully dispersed, functionalized NPs in a stable

suspension.

IR spectroscopy was utilized to characterize the surface of the IONPs before and after

the CDLE procedure with C6 as the secondary ligand (Figure 9). To facilitate a thorough

and robust spectroscopic analysis, a sample of C6-stabilized IONPs was also prepared using a known literature method, the ‘stripping protocol’,18 for the purpose of

comparison. The stripping protocol involved firstly stripping the oleate from the surface

of the NPs, then introducing the secondary ligand, which may leave residual surface-

bound oleate molecules or lead to irreversible NP aggregation during the process,

preventing re-dispersion.

ACS Paragon Plus Environment

39

ACS Applied Nano Materials

(a) (a)

(b) (b)

2.0

Normalised absorbance (offset)

Normalised absorbance (offset)

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

1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 3500

Page 40 of 57

3000

2500

2000

1500

1000

P=O stretch 1143 P-O-Fe 1143 1065 1146 1063

2.4 2.2 2.0

P-OH stretch 1024

1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2

0.0 1500 1400 1300 1200 1100 1000

(c) O HO P HO O

900

800

700

Wavenumber / cm-1

Wavenumber / cm-1

(d) N3

O

Fe

O

Fe

O

O P

O

N3

O O

O

Figure 9. (a) and (b) FTIR spectra recorded for (—) free C6 ligand; (—) C6-IONPs

prepared through CDLE; (—) C6-IONPs prepared using the stripping protocol; (c) the

structure of 2-azido-2-methyl-propionic acid 2-phosphonooxy-hexyl ester (C6); (d) the

proposed binding mechanism of C6 on the surface of IONPs based on the FTIR

analysis.

As can be seen in Figure 9, the bands from the C6 ligand associated with the –CH2 stretching vibrations of the hydrocarbon chain >Vas = 2929 and Vs ^ 2855 cm-1), those

ACS Paragon Plus Environment

40

Page 41 of 57 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

ACS Applied Nano Materials

arising from the azide group asymmetric vibrations >Vas = 2112 cm-1) and the strong absorption resulting from the carbonyl stretching vibration (~1740 cm-1) remained unchanged. There are, however, spectral changes visible between 1300 and 900 cm-1 (the region characteristic for phosphonic acid group P-O stretching bands48) for C6-

IONPs prepared using the stripping protocol, and the sample from the CDLE

experiment. The IR spectral region of interest, that which contains phosphonic acid vibrational bands, is shown enlarged in Figure 9(b). The peak at 1024 cm-1 in the spectrum of the free C6 ligand was assigned to the P-OH stretching vibration.52 It is

shown in this figure that after ligand exchange by either of the two methods, there is a

decrease in intensity of this peak due to loss of the P-OH moieties; additionally, there is a manifestation of a band at ~1065 cm-1 in both cases, which can be attributed to the PO-Fe vibration,48, 53-54 consistent with binding of the C6 ligand. More detailed analysis,

provided in the SI, indicates that the C6 molecules are adsorbed onto the IONP surface

through a bidentate binding mode (Figure S9). The IR study confirms successful CDLE

of OA by C6 ligands while preserving the size and monodispersity of the IONPs in

suspension, suggesting the generality of the approach.

ACS Paragon Plus Environment

41

ACS Applied Nano Materials 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 42 of 57

CONCLUSIONS

In summary, novel competition/depletion processes that can be used for either cluster

assembly or ligand exchange are described for non-aqueous IONP suspensions. These

represent a promising alternative to existing methods, as they do not cause an

accumulation of a thick organic layer around the IONPs, nor do they induce particle or

cluster aggregation. Furthermore, by utilizing a substrate to irreversibly bind the primary

ligands and “activate” the NPs for subsequent functionalization, the incoming ligands

are not required to have a higher affinity for the surface of the NPs than the

primary/outgoing ligands. This opens up the possibility for a wider range of secondary

ligands to be utilized for ligand exchange. It also offers the opportunity to employ more

than one type of secondary ligand at a time, with no extra effort required, to prepare

multi-functional NPs using mixed-ligand systems. The adsorption of ligands containing

terminal azide groups to the surface of IONPs, as demonstrated, also allows for further

functionalization with a wide range of moieties for multiple applications through ‘click

ACS Paragon Plus Environment

42

Page 43 of 57 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

ACS Applied Nano Materials

chemistry’. This opens up possibilities to produce tailored nanomaterials for biomedical

and bio-sensing applications. Finally, different reactor designs suitable for scaling up

competition/depletion processes (CSD and CDLE) have been successfully

demonstrated. In ongoing work, we are developing competition/depletion processes for

a wide range of NP types in more polar media, using the surface chemistry

requirements and approaches to process design identified in this study.

ASSOCIATED CONTENT

Supporting Information. Synthetic details for the preparation of 2-azido-2-methyl-

propionic acid 2-phosphonooxy-hexyl ester (C6), DLS profiles, infrared spectra and

detailed analysis, description of dialysis experiments, schematic representations of

selected binding modes.

AUTHOR INFORMATION

Corresponding Author

ACS Paragon Plus Environment

43

Page 44 of 57

ACS Applied Nano Materials 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

*E-mail: [email protected]

Author Contributions

The manuscript was written through contributions of all authors. All authors have given

approval to the final version of the manuscript.

ACKNOWLEDGMENT

The authors thank David Barr, Centre for Trace Element Analysis, University of Otago

for ICP-MS analysis, Alan Helliwell and John Wells, Department of Chemistry,

University of Otago for facilitating the development of the Teflon® cells and Jackson

Lyon for his graphics assistance. D.E.J. and C.J.M. gratefully acknowledge financial

support from the Marsden Fund (RSNZ), contract UOO1123, and D.F.B received

funding from Science Foundation Ireland, project 16/IA/4584).

ABBREVIATIONS C6, 2-azido-2-methyl-propionic acid 2 phosphonooxy-hexyl ester; CDLE, competition

driven ligand exchange; CSD, competitive stabilizer desorption; IONPs, iron oxide

ACS Paragon Plus Environment

44

Page 45 of 57 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

ACS Applied Nano Materials

nanoparticles; NP, nanoparticle; OA, oleic acid; OAm, oleylamine; TLC, thin layer

chromatography.

REFERENCES

(1) Zhang, X.-Q.; Xu, X.; Bertrand, N.; Pridgen, E.; Swami, A.; Farokhzad, O. C.

Interactions of Nanomaterials and Biological Systems: Implications to Personalized Nanomedicine. Adv. Drug Deliv. Rev. 2012, 64, 1363-1384.

(2) Jans, H.; Huo, Q. Gold Nanoparticle-Enabled Biological and Chemical Detection and Analysis. Chem. Soc. Rev. 2012, 41, 2849-2866.

(3) Pan, J.; Quan, L. N.; Zhao, Y.; Peng, W.; Murali, B.; Sarmah, S. P.; Yuan, M.;

Sinatra, L.; Alyami, N. M.; Liu, J.; Yassitepe, E.; Yang, Z.; Voznyy, O.; Comin, R.;

Hedhili, M. N.; Mohammed, O. F.; Lu, Z. H.; Kim, D. H.; Sargent, E. H.; Bakr, O. M.

Highly Efficient Perovskite-Quantum-Dot Light-Emitting Diodes by Surface Engineering.

Adv. Mater. 2016, 28, 8718-8725.

(4) Yin, Y.; Alivisatos, A. P. Colloidal Nanocrystal Synthesis and the Organic– Inorganic Interface. Nature 2004, 437, 664.

ACS Paragon Plus Environment

45

ACS Applied Nano Materials 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 46 of 57

(5) Wang, Y.; He, J.; Liu, C.; Chong, W. H.; Chen, H. Thermodynamics Versus Kinetics in Nanosynthesis. Angew. Chem. Int. Ed. 2015, 54, 2022-2051.

(6) Qian, X.; Li, J.; Nie, S. Stimuli-Responsive SERS Nanoparticles: Conformational Control of Plasmonic Coupling and Surface Raman Enhancement. J. Am. Chem. Soc. 2009, 131, 7540-7541.

(7) Si, K. J.; Chen, Y.; Shi, Q.; Cheng, W. Nanoparticle Superlattices: The Roles of Soft Ligands. Adv. Sci. 2018, 5, 1700179.

(8) Pellegrino, T.; Manna, L.; Kudera, S.; Liedl, T.; Koktysh, D.; Rogach, A. L.; Keller,

S.; Rädler, J.; Natile, G.; Parak, W. J. Hydrophobic Nanocrystals Coated with an

Amphiphilic Polymer

;b A General Route to Water Soluble Nanocrystals. Nano Lett.

2004, 4, 703-707.

(9) Wang, Y.; Wong, J. F.; Teng, X.; Lin, X. Z.; Yang, H. “Pulling” Nanoparticles into

;b Phase Transfer of Oleic Acid Stabilized Monodisperse Nanoparticles into

Aqueous Solutions of c=%"

' -

Nano Lett. 2003, 3, 1555-1559.

ACS Paragon Plus Environment

46

Page 47 of 57 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

ACS Applied Nano Materials

(10) Lala, N.; Lalbegi, S. P.; Adyanthaya, S. D.; Sastry, M. Phase Transfer of Aqueous

Gold Colloidal Particles Capped with Inclusion Complexes of Cyclodextrin and Alkanethiol Molecules into Chloroform. Langmuir 2001, 17, 3766-3768.

(11) Yang, Y.-W.; Sun, Y.-L.; Song, N. Switchable Host–Guest Systems on Surfaces.

Acc. Chem. Res. 2014, 47, 1950-1960.

(12) Feltham, H. L. C.; Dumas, C.; Mannini, M.; Otero, E.; Sainctavit, P.; Sessoli, R.; Meledandri, C. J.; Brooker, S. Proof of Principle: Immobilisation of Robust CuII3TbIIIMacrocycles on Small, Suitably Pre-Functionalised Gold Nanoparticles. Chem. Eur. J. 2017, 23, 2517-2521.

(13) Lattuada, M.; Hatton, T. A. Functionalization of Monodisperse Magnetic Nanoparticles. Langmuir 2007, 23, 2158-2168.

(14) Duan, H.; Kuang, M.; Wang, D.; Kurth, D. G.; Möhwald, H. Colloidally Stable

Amphibious Nanocrystals Derived from Poly{[2-(Dimethylamino)Ethyl] Methacrylate} Capping. Angew. Chem. 2005, 117, 1745-1748.

ACS Paragon Plus Environment

47

ACS Applied Nano Materials 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 48 of 57

(15) Impellizzeri, S.; McCaughan, B.; Callan, J. F.; Raymo, F. M. Photoinduced

Enhancement in the Luminescence of Hydrophilic Quantum Dots Coated with Photocleavable Ligands. J. Am. Chem. Soc. 2012, 134, 2276-2283.

(16) Fleming, D. A.; Thode, C. J.; Williams, M. E. Triazole Cycloaddition as a General Route for Functionalization of Au Nanoparticles. Chem. Mater. 2006, 18, 2327-2334.

(17) Mizuhara, T.; Saha, K.; Moyano, D. F.; Kim, C. S.; Yan, B.; Kim, Y.-K.; Rotello, V.

M. Acylsulfonamide-Functionalized Zwitterionic Gold Nanoparticles for Enhanced Cellular Uptake at Tumor Ph. Angew. Chem. Int. Ed. 2015, 54, 6567-6570.

(18) Smolensky, E. D.; Park, H.-Y. E.; Berquo, T. S.; Pierre, V. C. Surface

Functionalisation of Magnetic Iron Oxide Nanoparticles for MRI Applications - Effect of Anchoring Group and Ligand Exchange Protocol. Contrast Media Mol. Imaging 2010, 6,

189-199.

(19) Caragheorgheopol, A.; Chechik, V. Mechanistic Aspects of Ligand Exchange in Au Nanoparticles. Phys. Chem. Chem. Phys. 2008, 10, 5029-5041.

ACS Paragon Plus Environment

48

Page 49 of 57 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

ACS Applied Nano Materials

(20) Boles, M. A.; Ling, D.; Hyeon, T.; Talapin, D. V. The Surface Science of Nanocrystals. Nat. Mater. 2016, 15, 141.

(21) Bixner, O.; Lassenberger, A.; Baurecht, D.; Reimhult, E. Complete Exchange of

the Hydrophobic Dispersant Shell on Monodisperse Superparamagnetic Iron Oxide Nanoparticles. Langmuir 2015, 31, 9198-9204.

(22) Kovalenko, M. V.; Scheele, M.; Talapin, D. V. Colloidal Nanocrystals with Molecular Metal Chalcogenide Surface Ligands. Science 2009, 324, 1417.

(23) Dinkel, R.; Braunschweig, B.; Peukert, W. Fast and Slow Ligand Exchange at the Surface of Colloidal Gold Nanoparticles. J. Phys. Chem. C 2016, 120, 1673-1682.

(24) Bagaria, H. G.; Ada, E. T.; Shamsuzzoha, M.; Nikles, D. E.; Johnson, D. T.

Understanding Mercapto Ligand Exchange on the Surface of FePt Nanoparticles.

Langmuir 2006, 22, 7732-7737.

ACS Paragon Plus Environment

49

ACS Applied Nano Materials 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 50 of 57

(25) Stolarczyk, J. K.; Ghosh, S.; Brougham, D. F. Controlled Growth of Nanoparticle Clusters through Competitive Stabiliser Desorption. Angew. Chem. Int. Ed. 2009, 48,

175 –178.

(26) Ninjbadgar, T.; Fox, E. K.; Hierrezuelo, J.; El Haddassi, F.; Brougham, D. F.

Monodisperse Magnetic Nanoparticle Assemblies Prepared at Scale by Competitive Stabiliser Desorption. J. Mater. Chem. B 2015, 3, 8638-8643.

(27) Meledandri, C. J.; Stolarczyk, J. K.; Brougham, D. F. Hierarchical Gold-Decorated Magnetic Nanoparticle Clusters with Controlled Size. ACS Nano 2011, 5, 1747-1755.

(28) Stolarczyk, J. K.; Meledandri, C. J.; Clarke, S. P.; Brougham, D. F. Size

Selectable Nanoparticle Assemblies with Magnetic Anisotropy Tunable across the Superparamagnetic to Ferromagnetic Range. Chem. Commun. 2016, 52, 13337-13340.

(29) Borase, T.; Ninjbadgar, T.; Kapatenakis, A.; Roche, R.; O'Connor, R.; Kerskens,

C.; Heise, A.; Brougham, D. F. Stable Aqueous Dispersions of Glycopeptide-Grafted Selectably Functionalized Magnetic Nanoparticles. Angew. Chem. Int. Ed. 2013, 52,

3164-3167.

ACS Paragon Plus Environment

50

Page 51 of 57 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

ACS Applied Nano Materials

(30) Stolarczyk, J. K.; Deak, A.; Brougham, D. F. Nanoparticle Clusters: Assembly and Control Over Internal Order, Current Capabilities and Future Potential. Adv. Mater. 2016, 28, 5400-5424.

(31) Meledandri, C. J.; Brougham, D. F. Low Field Magnetic Resonance Techniques in the Development of Nanomaterials for Biomedical Applications. Anal. Methods 2012,

4, 331-341.

(32) Neivandt, D. J.; Gee, M. L.; Hair, M. L.; Tripp, C. P. Polarised Infrared Attenuated

Total Reflection for the in Situ Determination of the Orientation of Surfactant Adsorbed at the Solid/Solution Interface. J. Phys. Chem. B 1998, 102, 5107-5114.

(33) Meledandri, C. J.; Stolarczyk, J. K.; Ghosh, S.; Brougham, D. F. Nonaqueous

Magnetic Nanoparticle Suspensions with Controlled Particle Size and Nuclear Magnetic Resonance Properties. Langmuir 2008, 24, 14159-14165.

(34) Genkawa, T.; Kanematsu, W.; Shinzawa, H. Two-Dimensional (2D) Infrared (IR)

Correlation Spectroscopy for Dynamic Absorption Behavior of Oleic Acid (OA) onto Silica Gel. J. Mol. Struct. 2014, 1069 118–121.

ACS Paragon Plus Environment

51

ACS Applied Nano Materials 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 52 of 57

(35) Blyholder, G.; Adhikar, C.; Proctor, A. Structure and Orientation of Oleic Acid Adsorbed onto Silica Gel Colloids Surf. A 1995, 105, 151-158.

(36) Marshall, K.; Rochester, C. H. Infrared Study of the Adsorption of Oleic and Linolenic Acids onto the Surface of Silica Immersed in Carbon Tetrachloride. J. Chem.

Soc. Faraday Trans. 1975, 71, 1754-1761.

(37) Fahmi, M. Z.; Chang, J.-Y. Forming Double Layer-Encapsulated Quantum Dots for Bio-Imaging and Cell Targeting. Nanoscale 2013, 5, 1517-1528.

(38) Mourdikoudis, S.; Liz-Marzán, L. M. Oleylamine in Nanoparticle Synthesis. Chem.

Mater. 2013, 25, 1465-1476.

(39) Warring, S. L.; Beattie, D. A.; McQuillan, A. J. Surficial Siloxane-to-Silanol

Interconversion During Room-Temperature Hydration/Dehydration of Amorphous Silica Films Observed by ATR-IR and TIR-Raman Spectroscopy. Langmuir 2016, 32, 1568-

1576.

ACS Paragon Plus Environment

52

Page 53 of 57 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

ACS Applied Nano Materials

(40) Scott, R. P. W. The Silica Gel Surface and Its Interactions with Solvent and Solute in Liquid Chromatography. J. Chromatogr. Sci. 1980, 18, 297-306.

(41) Rivera, D.; Poston, P. E.; Uibel, R. H.; Harris, J. M. In Situ Adsorption Studies at

Silica/Solution Interfaces by Attenuated Total Internal Reflection Fourier Transform

Infrared

)

)";b Examination of Adsorption Models in Normal-Phase Liquid

Chromatography. Anal. Chem. 2000, 72, 1543-1554.

(42) Sun, S.; Hao, Z. Size-Controlled Synthesis of Magnetite Nanoparticles. J. Am.

Chem. Soc. 2002, 124, 8204–8205.

(43) Pérez-Mirabet, L.; Solano, E.; Martínez-Julián, F.; Guzman, R.; Arbiol, J.; Puig,

T.; Obradors, X.; Pomar, A.; Yanez, R.; Ros, J.; Ricart, S. One-Pot Synthesis of Stable

Colloidal Solutions of MFe2O4 Nanoparticles Using Oleylamine as Solvent and Stabiliser. Mater. Res. Bull. 2013, 48, 966-972.

(44) Roonasi, P.; Holmgren, A. A Fourier Transform Infrared (FTIR) and

Thermogravimetric Analysis (TGA) Study of Oleate Adsorbed on Magnetite NanoParticle Surface. Appl. Surf. Sci. 2009, 255, 5891-5895.

ACS Paragon Plus Environment

53

ACS Applied Nano Materials 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 54 of 57

(45) Berti, I. O. P. D.; Cagnoli, M. V.; Pecchi, G.; Alessandrini, J. L.; Stewart, S. J.;

Bengoa, J. F.; Marchetti, S. G. Alternative Low-Cost Approach to the Synthesis of

Magnetic Iron Oxide Nanoparticles by Thermal Decomposition of Organic Precursors.

Nanotechnology 2013, 24, 175601.

(46) Klokkenburg, M.; Hilhorst, J.; Erné, B. H. Surface Analysis of Magnetite Nanoparticles in Cyclohexane Solutions of Oleic Acid and Oleylamine. Vib. Spectrosc. 2007, 43, 243-248.

(47) O’Connell, M. A.; de Cuendias, A.; Gayet, F.; Shirley, I. M.; Mackenzie, S. R.;

Haddleton, D. M.; Unwin, P. R. Evanescent Wave Cavity Ring-Down Spectroscopy

(EW-CRDS) as a Probe of Macromolecule Adsorption Kinetics at Functionalized Interfaces. Langmuir 2012, 28, 6902-6910.

(48) White, M. A.; Johnson, J. A.; Koberstein, J. T.; Turro, N. J. Toward the Syntheses

of Universal Ligands for Metal Oxide Surfaces: Controlling Surface Functionality through Click Chemistry. J. Am. Chem. Soc. 2006, 128, 11356-11357.

ACS Paragon Plus Environment

54

Page 55 of 57 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

ACS Applied Nano Materials

(49) Paramonov, P. B.; Paniagua, S. A.; Hotchkiss, P. J.; Jones, S. C.; Armstrong, N.

R.; Marder, S. R.; Bredas, J.-L. Theoretical Characterisation of the Indium Tin Oxide Surface and of Its Binding Sites for Adsorption of Phosphonic Acid Monolayers. Chem.

Mater. 2008, 20, 5131-5133.

(50) Zhang, B.; Kong, T.; Xu, W.; Su, R.; Gao, Y.; Cheng, G. Surface Functionalisation of Zinc Oxide by Carboxyalkylphosphonic Acid Self-Assembled Monolayers. Langmuir 2010, 26, 4514-4522.

(51) Marchetti, P.; Jimenez Solomon, M. F.; Szekely, G.; Livingston, A. G. Molecular Separation with Organic Solvent Nanofiltration: A Critical Review. Chem. Rev. 2014,

114, 3EC.k 3F3/

(52) Socrates, G. Infrared and Raman Characteristic Group Frequencies, John Wiley

& Sons, Ltd: England, 2001.

(53) Zhao, C.; Gao, X.; Lu, H.; Yan, R.; Wang, C.; Ma, H. Spontaneous Formation of

Mono-N-Butyl Phosphate and Mono-N-Hexyl Phosphate Thin Films on the Iron Surface

ACS Paragon Plus Environment

55

ACS Applied Nano Materials 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 56 of 57

in Aqueous Solution and Their Corrosion Protection Property. RSC Adv. 2015, 5,

54420-54432.

(54) Raman, A.; Dubey, M.; Gouzman, I.; Gawalt, E. S. Formation of Self-Assembled Monolayers of Alkylphosphonic Acid on the Native Oxide Surface of SS316L. Langmuir 2006, 22, 6469-6472.

ACS Paragon Plus Environment

56

Page 57 of 57 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

ACS Applied Nano Materials

ACS Paragon Plus Environment