The Effect of the Addition of Electrolyte Solutions on the Ferning Patterns of Tears Collected from Normal Eye Subjects.

SIGNIFICANCE: The current study is the first report to describe the improvement of ferning patterns of human tears using electrolyte solutions. The results can help in the production of new artificial tears to improve the quality of tears. PURPOSE: This study aimed to investigate the effect of the addition of different volumes of various electrolyte solutions on ferning patterns of human tears. METHODS: Tear samples (20 µL) were collected from the right eye of 13 subjects (5 men and 5 women) aged 19 to 36 years (27.1 ± 5.1 years) with normal eyes. Then, 1 µL of each tear sample was dried on a microscopic glass slide, and obtained ferns were observed using light microscopy and graded using the 5-point tear ferning (TF) grading scale. Homogenous mixtures of each tear sample (0.5 µL) and different volumes (0.5 to 5 µL) of each electrolyte were prepared. A sample (1 µL) of each mixture was dried, and the ferns obtained were graded and compared with those of the corresponding tears collected from subjects before the addition of electrolyte solutions. RESULTS: After the addition of electrolyte solutions, the TF grades of tears collected from healthy humans were generally improved. Significant (Wilcoxon test) improvements have been seen in the TF grades of the tear samples after the addition of a solution of potassium chloride (P = .03), calcium chloride (P = .01), magnesium chloride hexahydrate (P = .002), and sodium dihydrogen phosphate (P = .002). No significant improvements in the TF grades were seen after the addition of sodium chloride solution (P = .33). CONCLUSIONS: Ferning grades of human tears improved with most of the electrolytes used.

Chemical approaches to the sulfation of small molecules: current progress and future directions.

Sulfation is one of the most important modifications that occur to a wide range of bioactive small molecules including polysaccharides, proteins, flavonoids, and steroids. In turn, these sulfated molecules have significant biological and pharmacological roles in diverse processes including cell signalling, modulation of immune and inflammation response, anti-coagulation, anti-atherosclerosis, and anti-adhesive properties. This Essay summarises the most encountered chemical sulfation methods of small molecules. Sulfation reactions using sulfur trioxide amine/amide complexes are the most used method for alcohol and phenol groups in carbohydrates, steroids, proteins, and related scaffolds. Despite the effectiveness of these methods, they suffer from issues including multiple-purification steps, toxicity issues (e.g., pyridine contamination), purification challenges, stoichiometric excess of reagents which leads to an increase in reaction cost, and intrinsic stability issues of both the reagent and product. Recent advances including SuFEx, the in situ reagent approach, and TBSAB show the widespread appeal of novel sulfating approaches that will enable a larger exploration of the field in the years to come by simplifying the purification and isolation process to access bespoke sulfated small molecules.

A Sulfuryl Group Transfer Strategy to Selectively Prepare Sulfated Steroids and Isotopically Labelled Derivatives.

The treatment of common steroids: estrone, estradiol, cortisol, and pregnenolone with tributylsulfoammonium betaine (TBSAB) provides a convenient chemoselective conversion of the steroids alcohol/phenol moiety to the corresponding steroidal organosulfate. An important feature of the disclosed methodology is the millimolar scale of the reaction, and the isolation of the corresponding steroid sulfates as their biologically relevant sodium salts without the need for ion-exchange chromatography. The scope of the method was further explored in the estradiol and pregnanediol steroid systems with the bis-sulfated derivatives. Ultimately, a method to install an isotopic label, deuterium (2H) combined with estrone sulfation is a valuable tool for its mass-spectrometric quantification in biological studies.

A novel exchange method to access sulfated molecules.

Organosulfates and sulfamates are important classes of bioactive molecules but due to their polar nature, they are both difficult to prepare and purify. We report an operationally simple, double ion-exchange method to access organosulfates and sulfamates. Inspired by the novel sulfating reagent, TriButylSulfoAmmonium Betaine (TBSAB), we developed a 3-step procedure using tributylamine as the novel solubilising partner coupled to commercially available sulfating agents. Hence, in response to an increasing demand for complementary methods to synthesise organosulfates, we developed an alternative sulfation route based on an inexpensive, molecularly efficient and solubilising cation exchanging method using off-the-shelf reagents. The disclosed method is amenable to a range of differentially substituted benzyl alcohols, benzylamines and aniline and can also be performed at low temperature for sensitive substrates in good to excellent isolated yield.