Disclosed herein are pyrazine derivatives of Formula I: Formula I; wherein each of X1 and X2 is independently —CONR7R9; and each of Y1 and Y2 is independently —NR48R49; and methods of using the same. The disclosed pyrazine derivatives include those having urea, amide, sulfonamide, thiourea, and/or carbamate substituents. Among the various aspects of the present invention are pyrazine derivatives that may be detected in vivo and used in a number of medical procedures (e.g., renal function monitoring). Without being bound by a particular theory, the pyrazine derivatives described herein may be designed to be hydrophilic, thus allowing for rapid renal clearance for continuous monitoring of renal function.