Types of SAMs

Some of the popular monolayer self-assembly chemistries include:

 Thiols, disulfides and thiols on gold, stainless steel [58,123].

 Silanes on silicon dioxide and hydroxy functionalised surfaces

[48,133].

 Fatty acids and phosph(on)ates on metal oxides [56,134].  Isonitriles on platinum [55].

2.5.3.1. Thiols

An alkanethiol molecule has three chemical entities that determine its assembly and the general formula is X(CH2)nSH. The head group contains

thiol sulfur (SH) and this acts as the driving force for the chemisorption of sulfur with the surface. The tail or terminal group (X) can feature one of several functionalities including a hydroxyl, amine and a carboxylic group. The terminal hydroxyl (OH) or carboxylic (COOH) groups of the monolayers are highly useful for the chemical transformations to achieve their desired functionality. Also, by reacting the carboxylic group of the thiol SAMs with an acid chloride (SOCl2), further reactions can be attained [123]. For example, if

the terminal group of the monolayer and the reacting group of the binding molecules have a carboxylic group, then in such cases, the COOH group of the monolayer can be modified to its corresponding acid chloride and the desired reaction can be achieved. Scheme 2-1 shows an example of reaction mediated using thionyl chloride.

Scheme 2-1 Reaction scheme showing the conversion of acetic acid to acetic anhydride using thionyl chloride

Thiols have been mainly used to modify gold surfaces since 1983 and their attachment has been well-studied and reported [58,127,131]. However, thiols have also been used to modify other metallic surfaces including iron and stainless steel. The alkanethiol monolayers formed on 316L stainless steel (the

letter ‘L’ represents low carbon content of 0.03% max. in the composition)

were not as stable as they are on gold surfaces due to the complex surface chemistry of 316L SS [58]. Thiols have been used for a variety of applications including corrosion protection, semi-conductors, biomaterial and biosensing applications [128,135].

2.5.3.2. Silanes

Similar to thiols on gold, the use of trichlorosilane monolayers on silica surfaces is popular owing to their excellent grafting properties to silica surfaces [134]. Silanes are also used in chromatographic techniques for the separation of molecules. Chlorine in the silane monolayer reacts with the hydroxylated surface to form a stable siloxane (Si-O-Si) bond. The use of silane monolayers on metal oxide surfaces such as glass, titanium, aluminium and cobalt- chromium were also studied in recent years for drug delivery [118,136,137]. Trichlorosilane monomers were observed to be highly reactive towards glass surfaces [120].

One of the problematic conditions for researchers with silane monolayers is to synthesise and purify these silane monomers. When the silane monolayers are assembled on a surface they display a high degree of monomer crosslinking, condensation and/or formation of multilayers due to siloxane linkages (Si-O- Si) [138]. Crosslinking was observed to be less stable compared to non-cross linked monomers and thus allowing the desorption of monolayers in a short period of time. Mani et al. [137] reported that the silane monolayers formed on a cobalt-chromium alloy surface were due to the covalent bonding of the SAMs with the alloy (Si-O-Cr and Si-O-W). However, their study reported that these monolayers remained ordered and bound to the alloy surface for only seven days under in vitro conditions [137]. Drug delivery from the implant surface for a longer period below the toxic level may be necessary for certain clinical applications. In such cases, this system cannot be used and therefore,

the use of alkoxysilanes instead of chlorosilanes (such as trialkoxysilane) may be a better option. However, their assembly requires multiple soaking and annealing steps to form well-ordered monolayers [120].

2.5.3.3. Phosphonate monolayers

Apart from thiols and silane monolayers, phosphonic acids have gained considerable interest in recent years due to their ability to bond to a range of metal oxide surfaces and their relatively improved hydrolytic stability under physiological conditions [129,139]. The use of phosphonic acid SAMs for surface modification is recent when compared to silanes and thiol SAMs [140]. Similar to thiol on gold, phosphonic acid monolayers adsorb on a metal surface with a tail-up orientation with a tilt angle (determined using evanescence reflection spectroscopy) of the hydrocarbon chains of about 30° with respect to the normal [141].

Phosphonates have three oxygens and a carbon directly attached to a phosphorous molecule. The binding mechanism of these phosphonic acid monolayers to metal oxide surfaces can be a monodentate, bidentate or tridentate as represented in Figure 2-12 [123,142]. This binding mechanism depends on both the surface and the nature of the organophosphorous compounds. Phosphonic acids bind to a metal oxide surface by the co- ordination of phosphoryl oxygen to Lewis acidic sites, followed by the condensation of P-OH groups with surface hydroxyl group or other surface oxygen species [143]. A Lewis acid is an electron-pair acceptor and a Lewis base is an electron pair donor. Thus, the Lewis theory suggests that acids react with bases to share a pair of electrons, without any change in the oxidation numbers of the atoms. Phosphonic acid SAMs form a metal phosphonate bond when adsorbed to a metal oxide surface (Ti-O-P). Adsorption of long chain alkyl phosphonic acid SAMs on metal oxides has been reported to offer densely packed and well-ordered SAMs [53,56,144,145]. Like silanes, phosphonic acid SAMs do not condense (condensation is a reaction in which two molecules or moieties combine to form a large molecule, together with the loss of a small molecule) in general due to the absence of homo-condensation

(reaction between the functional groups of the same molecule/moiety) of P-OH and P-O bonds at aqueous conditions [140].

Figure 2-12 Schematic representation of the binding mechanism of phosphonic acid SAMs to a metal surface.

Although phosphonic acid SAMs were reported to exhibit high stability, it depends on various parameters including the density and degree of ordering, interaction between the monolayers, size of its head group, spacer length and the reaction method used to chemisorb the monolayers to the surface [146]. Buckholtz et al. [130] attempted to study the effect of long alkyl chains of phosphonic acid monolayers on Ti6Al4V, titanium, aluminium and vanadium surfaces. The compared long alkyl chain consisted of carbon atoms in even numbers between 18 and 30. This study showed that the results were indicative

of the chain length on SAM’s stability. When even numbers of carbon atoms

were used, better packing of the molecules were witnessed than the odd numbers due to interdigitation (to become interlocked) [147]. Hsu et al. [148] proposed an air-liquid interface assisted method to form a smooth and a homogenous phosphonic acid SAMs on a silicon surface. However, the common method followed by most researchers is the simple immersion method since it is less complicated and in-expensive.

Tosatti et al. [149] studied the assembly of phosphate monolayers on rough and smooth titanium oxide coated glass surfaces. Their studies revealed that phosphonic SAMs were chemisorbed to both rough and smooth titanium surfaces. The structure and order of phosphonic acid based monolayers on silicon was studied by Dubey et al. [47] and compared with thiols on gold surfaces. It was reported that phosphonate monolayers can be used to form

well-ordered SAMs with methyl and hydroxyl groups for electrical and bio- sensing applications.

The stability of SAMs depends on the temperature, pH of the aqueous medium, ionic concentrations in the medium and its exposure to harsh environments such as UV or other high power radiations [123,140]. Bhure et al. [55] investigated the stability of phosphonic acid monolayers on Co-Cr surfaces and showed that the monolayers were highly stable when the surfaces were exposed to atmospheric conditions. In an another study, Kaufmann et al. [56] investigated the stability of phosphonic acid SAMs on an electropolished Co- Cr surfaces. This study concluded that the SAMs desorbed in a biphasic manner in Tris buffer solution with more desorption in the first three days followed by a slow and sustained release. Their initial fast release was accounted for by the desorption of physically bound molecules followed by the sustained release of the covalently bound molecules. An initial study by Mani et al. [53] showed that the most of the phosphonic acid SAMs adsorbed on a titanium surface desorbed in a day when immersed in Tris buffer solution at 37 °C. When exposed to ambient air, SAMs were stable for 14 days. However, in their later studies with an improved SAM adsorption procedure by heat treating the SAM coated surfaces, stable phosphonic acid SAMs were formed in solution [37]. Phosphonate monolayers are not only limited to oxide substrates; they are also used to modify hydroxyapatite and calcium carbonate [54,150]. However, the number of studies on these non-oxide surfaces is considerably lower than the oxide surfaces [140].