Abstract: Crosslinking reagents for protein modification are provided, which comprise four functional, leaving groups capable of reacting with amino acid residues on the protein chains, one pair at each end of a relatively rigid chemical spacer group comprising aromatic residues joined by amide linkages. Such crosslinking reagents react with hemoglobin to effect intramolecular crosslinking of two dimeric hemoglobin units to stabilize the tetramers, by use of the respective pairs of functional groups, and to produce dimers of such tetrameric units, i.e. bis-tetrameric, intramolecularly crosslinked and stabilized hemoglobin, to the exclusion of higher molecular weight hemoglobin species.

Abstract: Multifunctional chemical reagents useful in cross-linking hemoglobin and having the capability of leaving two or more reaction sites available for further chemical reactions, after completion of the cross-linking process. These reagents are broadly defied as aromatic compounds comprising an aromatic nucleus including but not limited phenyl, biphenyl, naphthyl and binaphthyl, with at least four independently selected electronegative substituent groups bonded directly or indirectly to the aromatic nucleus.

Abstract: A process for the preparation of acyl phosphate esters of the formula I or salts thereof: ##STR1## wherein R and R.sup.1 are the same or different and represent a linear or branched alkyl group having up to 4 carbon atoms, phenyl or benzyl;n is an integer;when n is 1, R.sup.2 represents the group ##STR2## wherein R.sup.4 is a linear or branched alkyl, alkenyl or alkynyl, a cyclic alkyl, a cyclic alkenyl, or aryl which may be substituted by alkyl, alkenyl, alkynyl, aryl, arylalkyl, or arylalkenyl, orwhen n is at least 2, R.sup.2 represents the group ##STR3## wherein R.sup.4 is as defined above. Novel compounds of the formula I wherein n is at least 2, and modified hemoglobin obtained using the novel compounds are also provided.