Methods and compounds for detecting beta-lactamase activity

A method of forming a compound of one of general formulas (I)-(III)

• wherein R1 is selected from the group consisting of H, halogen and
• wherein X is one of O, S, Se and NH,
• and R11 and R12 are independently from each other H or selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R2 is one of H, halogen, an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R3 to R5, in formulas (I) and (III) R6, and in formula (III) R10 are independently from each other selected H or one of an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R15 in formula (I), R16 in formula (II) and R17 in formula (III) are independently selected from H or one of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, including 0 to about 5 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• Z is S or Se;
• X is one of O, S, Se and NH;
• and
• A is a bridge selected from an aliphatic, alicyclic, aromatic, arylaliphatic, and arylalicyclic radical with a main chain of 1-50 carbon atoms and 0-50 heteroatoms;
• the method comprising reacting a compound of one of general formulas (XX), (XXX) and (XXXI):
• wherein L is a suitable leaving group,
• R6 in formulas (XX) and (XXXI) is H or one of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• and
• R13 is selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si,
• with a compound of general formula R14—Z-A-Z—R14 (L)
• wherein R14 in formula (L) is selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si.

A method of forming a compound of one of general formulas (VII) to (IX):

• wherein R1 is selected from the group consisting of H, halogen and
• wherein X is one of O, S, Se and NH,
• and R11 and R12 are independently from each other H or selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R2 is one of H, halogen, an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R3 to R5, in formulas (VII) and (IX) R6, R8 and R9 are independently from each other H or selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• E is one of S, SO, SO2, and CH2;
• X is one of O, S, Se and NH;
• Z is S or Se;
• and
• G is a bridge selected from an aliphatic, alicyclic, aromatic, arylaliphatic, and arylalicyclic radical with a main chain of 1-50 carbon atoms and 0-50 heteroatoms;
• the method comprising reacting a compound of one of general formulas (XX), (XXX) and (XXXI):
• wherein L is a suitable leaving group,
• R13 is selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si,
• R6 in formulas (XX) and (XXXI) is H or one of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si, and
• X is one of O, S, Se and NH;
• with a compound of general formula (LII)
• wherein R8 and R9 are independently from each other selected H or one of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• and
• R14 is selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si.

A kit for detecting beta-lactamase activity in a sample, the kit comprising:

• a compound of one of general formulas (I)-(III) and (VII)-(IX):
• wherein R1 is selected from the group consisting of H, halogen and
• wherein X is one of O, S, Se and NH,
• and R11 and R12 are independently from each other H or selected from the group consisting of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R2 is one of H, halogen, an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R3 to R5, to R5, in formulas (I), (III), (VII) and (IX) R6, in formulas (VII)-(IX) R8 and R9, and in formulas (III) and (IX) R10, are independently from each other selected H or one of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• R15 in formula (I), R16 in formula (II) and R17 in formula (III) are independently selected from H or one of an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, including 0 to about 5 heteroatoms selected from the group consisting of N, O, S, Se and Si;
• X in formulas (III) and (IX) is one of O, S, Se and NH;
• E is one of S, SO, SO2, and CH2;
• Z is S or Se;
• and
• A in formulas (I)-(III) and G in formulas (VII)-(IX) are independently from each other a bridge selected from an aliphatic, alicyclic, aromatic, arylaliphatic, and arylalicyclic radical with a main chain of 1-50 carbon atoms and 0-50 heteroatoms;
• and
• a nanoparticulate tag.