**4. Conclusions**

By using the design of experiments (DOE) methodology, six reaction factors were identified and optimized to maximize the degree of functionalization of inorganic WS2 INTs with a carboxylic acid shell via a modified highly electrophilic Vilsmeier–Haack reaction. Initial studies produced functionalized INTs with 0.5 mmol COOH groups per gram of INT as quantified by the Kaiser test. Moreover, a statistically relevant DOE global optimization resulted in functionalization increasing by a factor of 2.4 to 1.2 mmol of accessible COOH groups per gram of chemically-modified INTs. Time, temperature and amount of silver acetate (Ag(I)OAc) were found to be the most important factors that affect the functionalization yield.

In addition, contour plots of interacting reaction parameters suggest that it may be possible to control the amount of polyCOOH functionalization by tuning the amounts of INTs, 2-bromoacetic acid, DMF and Ag(I)OAc in the reaction mixture in conjunction with reaction temperature. This attractive capability may prove valuable for optimizing the use of functionalized WS2 INTs in important applications, such as functional nanoscale fillers for the mechanical reinforcement of polymeric matrices with optimal interfacial phase interactions.
